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Nicchio IG, Cirelli T, Quil LCDC, Camilli AC, Scarel-Caminaga RM, Leite FRM. Understanding the peroxisome proliferator-activated receptor gamma (PPAR-γ) role in periodontitis and diabetes mellitus: A molecular perspective. Biochem Pharmacol 2025; 237:116908. [PMID: 40157459 DOI: 10.1016/j.bcp.2025.116908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 02/19/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Periodontitis and Type 2 Diabetes Mellitus (T2DM) are chronic conditions with dysregulated immune responses. Periodontitis involves immune dysfunction and dysbiotic biofilms, leading to tissue destruction. T2DM is marked by insulin resistance and systemic inflammation, driving metabolic and tissue damage. Both conditions share activation of key pathways, including Nuclear Factor Kappa B (NF-κB), Activator Protein-1 (AP-1), and Signal Transducer and Activator of Transcription (STAT) proteins, reinforcing an inflammatory feedback loop. This review highlights the role of Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ), a transcription factor central to lipid and glucose metabolism, adipogenesis, and immune regulation. PPAR-γ activation has been shown to suppress inflammatory mediators such as Tumor Necrosis Factor Alpha (TNF-α) and Interleukin 6 (IL-6) through the inhibition of NF-κB, AP-1, and STAT pathways, thereby potentially disrupting the inflammatory-metabolic cycle that drives both diseases. PPAR-γ agonists, including thiazolidinediones (TZDs) and endogenous ligands such as 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), show promise in reducing inflammation and improving insulin sensitivity, but they are limited by adverse effects. Therapies, including Selective Peroxisome Proliferator-Activated Receptor Modulators (SPPARMs), have been developed to offer a more targeted approach, allowing for selective modulation of PPAR-γ activity to retain its anti-inflammatory benefits while minimizing their side effects. By integrating insights into PPAR-γ's molecular mechanisms, this review underscores its therapeutic potential in mitigating inflammation and enhancing metabolic control.
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Affiliation(s)
- Ingra Gagno Nicchio
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil; Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil.
| | - Thamiris Cirelli
- Department of Dentistry, Centro Universitário das Faculdades Associadas, São João da Boa Vista 13870-377, SP, Brazil.
| | - Lucas César da Costa Quil
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil; Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil.
| | - Angelo Constantino Camilli
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil.
| | - Raquel Mantuaneli Scarel-Caminaga
- Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-903, SP, Brazil.
| | - Fabio Renato Manzolli Leite
- National Dental Research Institute Singapore, National Dental Centre Singapore, 168938, Singapore; Oral Health Academic Clinical Programme, Duke-NUS Medical School, 169857, Singapore.
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Cai Y, Guo T, Zhou J, Zhang H, Li T, Zhi Z, Wang P, Cui M, Hu Z, Zhang J. Alpha-Linolenic Acid from Zanthoxylum Seed Powder Regulates Fatty Acid Metabolism and Influences Meat Quality of Pekin Duck via the ADIPOQ/AMPK/CPT-1 Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:14651-14665. [PMID: 40459020 PMCID: PMC12164340 DOI: 10.1021/acs.jafc.5c01995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 05/21/2025] [Accepted: 05/22/2025] [Indexed: 06/16/2025]
Abstract
Zanthoxylum seed powder contains dominant α-linolenic acid (ALA). Its regulatory mechanism as a novel feed additive for the livestock field is not clear. In this study, RNA-seq was used to identify the differential gene expression in breast muscle of Pekin duck supplemented with different doses of Zanthoxylum seed powder, and Adiponectin (ADIPOQ) was found to be an important factor. Functional validation was performed in duck primary myoblasts. Our results revealed that ADIPOQ overexpression could promote myoblast myotube fusion, that is, myogenic differentiation. On the other hand, ALA inhibited lipid deposition in myoblasts. SiADIPOQ inhibited fatty acid oxidation, but stimulated fatty acid synthesis and transport. Furthermore, ALA promoted the up-regulation of ADIPOQ, AMPK, p-AMPK and CPT-1 protein levels. It was concluded that ALA regulates lipid deposition through the ADIPOQ/AMPK/CPT-1 pathway in myoblasts. These results may provide theoretical basis for the development and utilization of Zanthoxylum seed powder in duck production.
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Affiliation(s)
- Yingjie Cai
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Tong Guo
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Jie Zhou
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Huiya Zhang
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Tao Li
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Zhuo Zhi
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Peng Wang
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Mengmeng Cui
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Zhigang Hu
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
| | - Jianqin Zhang
- College of Animal Science
and Technology, Northwest A&F University, Yangling, Shaanxi712100, P. R. China
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Kafeel S, Palmiero G, Salzillo A, Ragone A, Naviglio S, Sapio L. Unravelling the Adiponectin Hallmark and Exploring the Therapeutic Potential of Its Receptor Agonists in Cancer Metabolic Reprogramming. Biomolecules 2025; 15:820. [PMID: 40563460 DOI: 10.3390/biom15060820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2025] [Revised: 05/29/2025] [Accepted: 06/01/2025] [Indexed: 06/28/2025] Open
Abstract
As the most abundant fat-derived hormone, adiponectin plays an essential role in regulating energy homeostasis. Current evidence proposes the serum levels of adiponectin as a risk factor and a diagnostic/prognostic biomarker in cancer. Moreover, distinctive antineoplastic features have also been reported as a result of adiponectin supplementation in preclinical models. Mapping of the cancer-associated metabolic changes has elucidated a highly adaptable and interconnected system that allows malignant cells to sustain their growth and survival. Along with the pyruvate into acetyl-CoA conversion, downregulation of both lactate dehydrogenase and glycolysis-related genes depicts the main adiponectin-induced perturbations affecting glucose metabolism in cancer. Meanwhile, a multi-level approach involving lipid trafficking, catabolism, and de novo synthesis has been attributed to adiponectin in malignancies. The adiponectin receptor agonist AdipoRon has recently been recognized as a promising antineoplastic compound. Remarkably, AdipoRon-mediated changes in cancer metabolism occur together with its antiproliferative potential. This review aimed at recapitulating the modulatory effects of adiponectin, as well as those of its synthetic receptor agonists, in driving metabolic alterations in cancerous cells. A critical discussion is also conducted to deduce whether the adiponectin axis could serve as a putative target to address the metabolic reprogramming in cancer progression.
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Affiliation(s)
- Sanober Kafeel
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Giuseppina Palmiero
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Alessia Salzillo
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Angela Ragone
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
- Department of Mechanistic Cell Biology, Max Plank Institute of Molecular Physiology, 44227 Dortmund, Germany
| | - Silvio Naviglio
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Luigi Sapio
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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Islam K, Islam R, Nguyen I, Malik H, Pirzadah H, Shrestha B, Lentz IB, Shekoohi S, Kaye AD. Diabetes Mellitus and Associated Vascular Disease: Pathogenesis, Complications, and Evolving Treatments. Adv Ther 2025; 42:2659-2678. [PMID: 40252164 PMCID: PMC12085338 DOI: 10.1007/s12325-025-03185-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 03/19/2025] [Indexed: 04/21/2025]
Abstract
Diabetes mellitus is a metabolic disorder, characterized by elevated blood sugar levels (hyperglycemia) and insulin dysregulation. This disease is associated with morbidity and mortality, including significant potential vascular complications. High levels of hyperglycemia lead to not only elevated levels of reactive oxygen species but also advanced glycation end products, which are detrimental to the vascular endothelium and reduce protective compounds such as nitric oxide and prostacyclin. This damage contributes to the development of both macrovascular and microvascular complications. The present investigation explores the pathophysiological mechanisms of diabetic vascular complications and evaluates current management strategies, including lifestyle modifications, pharmacological treatments, and emerging therapies. The review underscores the importance of ongoing progress in diabetes management and patient education to lead to optimal patient-health outcomes and quality of life for individuals with diabetes mellitus.
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Affiliation(s)
- Kazi Islam
- Central State University, 1400 Brush Row Road, Wilberforce, OH, 45384, USA
| | - Rahib Islam
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Ivan Nguyen
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Hassan Malik
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Humza Pirzadah
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Barsha Shrestha
- LSU Health Sciences Center New Orleans School of Medicine, 1901 Gravier Street, New Orleans, LA, 70112, USA
| | - Isabella B Lentz
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
| | - Sahar Shekoohi
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
- Department of Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA
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Singal AM, Howard VJ, Judd SE, Carson AP, Zakai NA, Olson NC, Cushman M, Plante TB. Association between serum adiponectin and risk of incident hypertension: the REGARDS study. J Hypertens 2025:00004872-990000000-00684. [PMID: 40366102 DOI: 10.1097/hjh.0000000000004057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 04/24/2025] [Indexed: 05/15/2025]
Abstract
INTRODUCTION Hypertension is a cardiovascular disease risk factor disproportionately affecting Black adults. Adiponectin is a cytokine secreted by adipocytes that improves insulin sensitivity, maintains vascular homeostasis, and is inversely associated with adiposity. We sought to determine the risk of incident hypertension by level of adiponectin. METHODS The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 adults from 2003 to 2007. We included REGARDS participants in the Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) substudy. We estimated the risk ratio for incident hypertension in unadjusted and adjusted models for demographics factors, dietary patterns, measures of adiposity, and SBP. RESULTS Inverse odds ratio weighting estimated the excess hypertension incidence among Black participants that was explained by adiponectin. Of the 1498 BioMedioR participants, 35% developed incident hypertension in follow-up. White adults had higher baseline adiponectin levels than Black adults. For each 1-SD higher log adiponectin, the risk ratio of hypertension was 0.90 [95% confidence interval (95% CI) 0.84-0.96] in an unadjusted model, 0.92 (0.86-1.00) in a demographic adjusted model, and 0.99 (0.91-1.07) in a fully adjusted model. Lower adiponectin mediated 21-46% of the excess risk of incident hypertension among Black relative to White participants in models adjusting for just demographics and dietary patterns. CONCLUSION Among Black and White adults, lower adiponectin was associated with a greater risk of incident hypertension in unadjusted and minimally adjusted models. Future studies into how adiponectin changes in obesity could help to further explain its impact on hypertension risk.
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Affiliation(s)
- Aneesh M Singal
- Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts
| | | | - Suzanne E Judd
- University of Alabama at Birmingham, Birmingham, Alabama
| | - April P Carson
- University of Mississippi Medical Center, Jackson, Mississippi
| | - Neil A Zakai
- University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Nels C Olson
- University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Mary Cushman
- University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - Timothy B Plante
- University of Vermont Larner College of Medicine, Burlington, Vermont, USA
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Xu X, Tang X, Ji R, Xiang X, Liu Q, Han S, Du J, Li Y, Mai K, Ai Q. Adiponectin receptor agonist AdipoRon regulates glucose and lipid metabolism via PPARγ signaling pathway in hepatocytes of large yellow croaker (Larimichthys crocea). Biochim Biophys Acta Mol Cell Biol Lipids 2025; 1870:159632. [PMID: 40379087 DOI: 10.1016/j.bbalip.2025.159632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 05/07/2025] [Accepted: 05/13/2025] [Indexed: 05/19/2025]
Abstract
Activation of adiponectin receptors (AdipoRs) has been shown to regulate glucose and lipid metabolism in mammalian hepatocytes. However, much less is known for their roles in fish. The current study demonstrated that AdipoRon, a small-molecule activator of AdipoRs, modulated glucose and lipid metabolism in large yellow croaker. In hepatocytes of large yellow croaker, AdipoRon upregulated the mRNA expression of adipors and appl1, while increasing phosphorylation levels of AMPK and AKT. These changes indicate the activation of AdipoR-mediated signaling. Furthermore, AdipoRon promoted glucose uptake, increased intracellular glucose content, as well as upregulated genes involved in glycogen synthesis and glycolysis whereas downregulated gluconeogenesis-related genes. On the other hand, AdipoRon facilitated free fatty acid (FFA) absorption by increasing the expression of fatty acid transport genes (fat/cd36, fatp1, and fabp11). It also enhanced triglyceride (TG) synthesis, evidenced by increased triglyceride levels and upregulation of dgat2 and PPARγ, which is consistent with the effect of adiponectin (APN) in large yellow croaker. Additional evidence suggested that inhibition of PPARγ with GW9662 reduced the effects of AdipoRon on glucose uptake and lipid metabolism, indicating that PPARγ is a key mediator in these metabolic regulations. Overall, AdipoRon was found to modulate multiple metabolic processes in hepatocytes of large yellow croaker via PPARγ signaling pathway, and these findings suggested that AdipoRon might contribute to beneficial effects on metabolic homeostasis in teleosts.
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Affiliation(s)
- Xiang Xu
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Xiao Tang
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Renlei Ji
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Xiaojun Xiang
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Qiangde Liu
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Shangzhe Han
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Jianlong Du
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Yueru Li
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Kangsen Mai
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China
| | - Qinghui Ai
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People's Republic of China.
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Liu X, Lou Y, Chang Z, Gu C, Du B, Sun G. Associations of obesity defined comprehensively by body mass index and body fat percentage with osteopenia. Clinics (Sao Paulo) 2025; 80:100674. [PMID: 40344912 DOI: 10.1016/j.clinsp.2025.100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/27/2025] [Accepted: 04/15/2025] [Indexed: 05/11/2025] Open
Abstract
OBJECTIVE To explore the association of obesity comprehensively defined by Body Mass Index (BMI) and Body Fat percentage (BF%) with osteopenia. METHODS In this cross-sectional study, data of adult men and postmenopausal women aged ≥ 50 years old were obtained from the National Health and Nutrition Examination Surveys (NHANES) database. Weighted logistic regression analysis was conducted to investigate the association of BF% obesity with osteopenia in participants who had different gender and BMI obesity conditions. The association of obesity comprehensively evaluated by BMI and BF% with osteopenia was also explored in the total population and in gender subgroups. RESULTS Among 1720 eligible subjects, 1054 had osteopenia. Multivariate analysis suggested that in males, BMI obesity combined with BF% obesity was associated with higher osteopenia odds compared to BMI obesity only (Odds Ratio [OR = 4.01], 95% Confidence Interval [95% CI 1.43‒11.27]). Compared to participants with both BMI and BF% obesity, those with BMI obesity have lower osteopenia odds (OR = 0.46, 95% CI 0.28‒0.76), whereas those with BF% obesity have higher odds of osteopenia (OR = 2.03, 95% CI 1.35‒3.05, p = 0.002). In females, compared to BMI obesity combined with BF% obesity, BF% obesity (OR = 3.37, 95% CI 1.47‒7.73) or non-obesity (OR = 2.11, 95% CI 1.18‒3.75) was respectively associated with higher osteopenia odds. In males, BMI obesity was linked to lower osteopenia odds compared to both BMI and BF% obesity (OR = 0.25, 95% CI 0.10‒0.62). CONCLUSIONS The comprehensively assessed obesity by BMI and BF% may be more meaningful in the evaluation of potential osteopenia risk, as well as further prevention and intervention of osteoporosis.
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Affiliation(s)
- Xin Liu
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China
| | - Yan Lou
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China
| | - Zhiyong Chang
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China
| | - Changyuan Gu
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China
| | - Bin Du
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China
| | - Guangquan Sun
- Department of Orthopedics and Traumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, PR China.
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Liu H, Xiang R, Liu C, Chen Z, Shi Y, Liu Y, Liu Y. Association between cardiometabolic index and bone mineral density among adolescents in the United States. Front Endocrinol (Lausanne) 2025; 16:1535509. [PMID: 40405970 PMCID: PMC12095025 DOI: 10.3389/fendo.2025.1535509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 04/14/2025] [Indexed: 05/26/2025] Open
Abstract
Objectives The cardiometabolic index (CMI) serves as a comprehensive metric for evaluating cardiometabolic health, and is correlated with several health outcomes. However, research examining the relationship between CMI and bone mineral density (BMD), particularly in adolescent populations, remains limited and warrants further investigation. Methods The weighted multiple linear regression analysis was conducted to elucidate the association between CMI and BMD. Results Our study ultimately included 1,514 participants. After adjusting for pertinent covariates, we observed that per-unit increases in the CMI corresponded with reductions in BMD by 0.052 g/cm2 for femoral neck (β=-0.052, 95% CI: -0.087 to -0.018) and 0.048 g/cm2 for lumbar spine (L1-L4) (β=-0.048, 95% CI: -0.085 to -0.011). In quartile analyses, individuals in the highest quartile displayed significantly reduced BMD at the femoral neck (β=-0.036, 95% CI: -0.064 to -0.007) and lumbar spine (L1-L4) (β=-0.041, 95% CI: -0.070 to -0.011) compared to those in the lowest quartile (P<0.05). No statistical significance was detected between CMI and BMD at the total femur, trochanter, and intertrochanter sites. Furthermore, stratified analyses indicated no significant interactions involving age, sex, or race in relation to CMI and BMD. Conclusions In the adolescent population, CMI is inversely related to BMD. These findings highlight a potential link between cardiometabolic health and bone health. Future longitudinal investigations are warranted to determine causal relationships and underlying mechanisms.
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Affiliation(s)
- Haobiao Liu
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Rongqi Xiang
- Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Chenyue Liu
- Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhuohang Chen
- Department of Epidemiology, School of Public Health, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Yuhang Shi
- School of Basic Medical Sciences, Shanghai Jiaotong University, Shanghai, China
| | - Yiting Liu
- Faculty of Medicine, Dentistry and Health Sciences, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Yan Liu
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Ivashkevich D, Ponomarenko A, Manzhulo I, Egoraeva A, Dyuizen I. Hepatoprotective and Antiatherosclerotic Effects of Oleoylethanolamide-Based Dietary Supplement in Dietary-Induced Obesity in Mice. PATHOPHYSIOLOGY 2025; 32:16. [PMID: 40265441 PMCID: PMC12015875 DOI: 10.3390/pathophysiology32020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 04/24/2025] Open
Abstract
Background: Metabolic effects of oleoylethanolamide-based dietary supplement (OEA-DS) were studied in a model of dietary-induced obesity in mice. Obesity was induced by a 2-month high-fat, high-cholesterol diet, resulting in significant morphological changes in liver tissues and elevated cholesterol levels in the animals' blood serum. Elevated levels of proinflammatory cytokines, oxidative stress, and hepatocyte apoptosis were also observed in the liver tissue. The aim of this study was to examine the mechanisms through which an OEA-based dietary supplement (OEA-DS) exerts a comprehensive influence on multiple aspects of the pathogenesis of MASLD, thereby demonstrating a robust hepatoprotective effect. Methods: mice were fed a high-fat, high-cholesterol diet with or without OEA-DS supplementation. Liver tissues and blood serum were analyzed for cholesterol levels, inflammatory markers (CD68, Iba-1, CD163, IL-1β, IL-6, TNFα), apoptotic markers (Bad, Bax, Bcl-2), nuclear receptors (PPAR-α, PPAR-γ, AdipoR1), and enzymes involved in lipolysis (Acox1, Cpt1a) and cholesterol metabolism (Ldlr, Furin, Pcsk9). Immunohistochemistry, Western blotting, and RT-PCR were used to assess protein expression and gene transcription. Results: administration of OEA-DS normalized cholesterol levels, decreased expression of inflammatory markers (CD68 and Iba-1), pro-apoptotic markers (Bad, Bax) and levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα). In parallel, the expression of nuclear receptors PPAR-α and PPAR-γ, adiponectin receptor 1 (AdipoR1), and anti-inflammatory (CD163) and anti-apoptotic (Bcl-2) markers have risen. OEA-DS administration induced the expression of liver lipolysis enzymes (Acox1, Cpt1a) and cholesterol metabolism factors (Ldlr, Furin), while simultaneously reducing the transcription of the proatherogenic factor Pcsk9. Conclusions: The results of this study suggest a complex action of OEA-DS in obesity-associated liver damage, which includes reduction of systemic inflammation.
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Affiliation(s)
| | | | - Igor Manzhulo
- A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str., 17, 690041 Vladivostok, Russia; (D.I.); (A.P.); (A.E.); (I.D.)
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10
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Catana OM, Nemes AF, Cioboata R, Toma CL, Mitroi DM, Calarasu C, Streba CT. Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis-A Narrative Review. J Clin Med 2025; 14:2611. [PMID: 40283443 PMCID: PMC12027990 DOI: 10.3390/jcm14082611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/06/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations and systemic inflammation. The interaction between the metabolic and inflammatory pathways plays a key role in disease progression, with leptin and insulin emerging as pivotal metabolic regulators. Leptin, an adipokine that regulates energy homeostasis, and insulin, the primary regulator of glucose metabolism, are both altered in COPD patients. This narrative review provides an in-depth examination of the roles of leptin and insulin in COPD pathogenesis, focusing on the molecular mechanisms through which these metabolic regulators interact with inflammatory pathways and how their dysregulation contributes to a spectrum of extrapulmonary manifestations. These disturbances not only exacerbate COPD symptoms but also increase the risk of comorbidities such as metabolic syndrome, diabetes, cardiovascular disease, or muscle wasting. By exploring the underlying mechanisms of leptin and insulin dysregulation in COPD, this review underscores the significance of the metabolic-inflammatory axis, suggesting that restoring metabolic balance through leptin and insulin modulation could offer novel therapeutic strategies for improving clinical outcomes.
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Affiliation(s)
- Oana Maria Catana
- Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania; (O.M.C.); (D.M.M.)
| | | | - Ramona Cioboata
- Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.C.); (C.T.S.)
| | - Claudia Lucia Toma
- Pneumology Department, University of Medicine Carol Davila, 020021 Bucharest, Romania
| | - Denisa Maria Mitroi
- Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania; (O.M.C.); (D.M.M.)
| | - Cristina Calarasu
- Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.C.); (C.T.S.)
| | - Costin Teodor Streba
- Pneumology Department, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.C.); (C.T.S.)
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11
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Ohshima K, Miyano K, Nonaka M, Aiso S, Fukuda M, Furuya S, Fujii H, Uezono Y. The Flavonoids and Monoterpenes from Citrus unshiu Peel Contained in Ninjinyoeito Synergistically Activate Orexin 1 Receptor: A Possible Mechanism of the Orexigenic Effects of Ninjinyoeito. Biomolecules 2025; 15:533. [PMID: 40305263 PMCID: PMC12025248 DOI: 10.3390/biom15040533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 05/02/2025] Open
Abstract
Cancer cachexia, often observed in patients with advanced-stage cancer, is characterized by the loss of body weight and appetite. The Japanese herbal medicine Ninjinyoeito (NYT), which is composed of 12 crude herbal components, has been used as a therapeutic in Japan to improve anorexia and fatigue, which are commonly observed in cancer patients with cachexia. We have previously reported that Citrus unshiu peel (CUP) contained in NYT can enhance food intake by activating the orexin 1 receptor (OX1R). Using the CellKey™ system, which offers detection of OXR activity in intracellular impedance changes, NYT and CUP were found to activate OX1R, which in turn was inhibited by SB-674042, a selective OX1R antagonist. Among the flavonoids contained in CUP, nobiletin and hesperidin, but not naringin, activated OX1R. Furthermore, some monoterpenes contained in CUP, including limonene and linalool, but not terpineol, activated OX1R. In addition, nobiletin and limonene synergistically activated OX1R when added simultaneously. However, neither NYT nor CUP induced OX2R activity. The results collectively suggested that the CUP contained in NYT activates OX1R, but not OX2R, and that flavonoids and monoterpenes in CUP can synergistically activate OX1R. These findings could provide evidence supporting the therapeutic potential of NYT in cancer patients with cachexia.
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Affiliation(s)
- Kaori Ohshima
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Department of Pathology, Immunology, and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
| | - Kanako Miyano
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Laboratory of Pharmacotherapeutics, Faculty of Pharmacy, Juntendo University, Chiba 279-0013, Japan
| | - Miki Nonaka
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Center for Neuroscience of Pain, The Jikei University School of Medicine, Tokyo 105-8461, Japan
| | - Sayaka Aiso
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan;
| | - Mao Fukuda
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan;
| | - Saho Furuya
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan;
| | - Hideaki Fujii
- Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan;
| | - Yasuhito Uezono
- Department of Pain Control Research, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (K.O.); (K.M.); (M.N.); (S.A.); (M.F.); (S.F.)
- Center for Neuroscience of Pain, The Jikei University School of Medicine, Tokyo 105-8461, Japan
- Pharmacological Department of Herbal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
- Department of Comprehensive Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
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12
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Neves D, Neto AC, Salazar M, Fernandes AS, Martinho M, Charrua A, Rodrigues AR, Gouveia AM, Almeida H. A narrative review about the intricate crosstalk among endometrium, adipose tissue, and neurons in endometriosis. The multifaceted role of leptin. Obes Rev 2025; 26:e13879. [PMID: 39657320 DOI: 10.1111/obr.13879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 10/31/2024] [Accepted: 11/17/2024] [Indexed: 12/12/2024]
Abstract
Endometriosis is a highly prevalent gynecological disease characterized by the presence of endometrium-like tissue outside the uterus, whose etiopathology is far from being elucidated. The most frequent complains of patients are pelvic pain and infertility. Increasing evidence supports the systemic impact of endometriosis suggesting that an intricate crosstalk among distinct organs underlies the development of the disease. In this setting, endometriosis patients present an increased risk for developing other diseases, such as cancer, cardiovascular pathologies, and autoimmune diseases, and manifest neurologic disturbances, including neuropathic hyperalgesia. Whilst the ovary-secreted estrogen dependency of ectopic endometrium growth is well established, we conjecture that adipose tissue-secreted molecules also intervene in endometriosis development and pain manifestation. In fact, women with endometriosis present a peculiar pattern of adipokine secretion that ensues the disease onset. Unexpectedly, the levels of adipose tissue-secreted molecules in those women present similarities with those found in patients with obesity, despite the recognized association of low body mass index with endometriosis. Taking this evidence into consideration, we hypothesize that endometriosis patients present a dysfunctional adipose tissue, which is associated with enhanced metabolism and unregulated browning that not only intervene in the control of body weight but also in peculiar pain processing pathways.
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Affiliation(s)
- Delminda Neves
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Ana Catarina Neto
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Maria Salazar
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Ana Sofia Fernandes
- Department of Obstetrics and Gynecology, Faculty of Medicine of the University of Porto, Porto, Portugal/Centro Hospitalar Universitário S. João, Porto, Portugal
| | - Margarida Martinho
- Department of Obstetrics and Gynecology, Faculty of Medicine of the University of Porto, Porto, Portugal/Centro Hospitalar Universitário S. João, Porto, Portugal
| | - Ana Charrua
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- RISE-HEALTH@FMUP, Porto, Portugal
| | - Adriana Raquel Rodrigues
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Alexandra Maria Gouveia
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
| | - Henrique Almeida
- Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal
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Lin F, Gilbertson TA. Fat taste responsiveness, but not dietary fat intake, is affected in Adipor1 null mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.12.642880. [PMID: 40161824 PMCID: PMC11952482 DOI: 10.1101/2025.03.12.642880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Taste is a major driving force that influences food choices and dietary intake. Adiponectin has been shown to selectively enhance cellular responses to fatty acids by mediating the activation of AMPK and translocation of CD36 in taste cells via its receptor AdipoR1. Whether Adipor1 gene knockout affects fat taste responsiveness and dietary fat intake in animals remains unclear. In the present study, we evaluated cellular, neural, and behavioral responses to fat, as well as the dietary fat intake in global Adipor1 knockout mice and their WT controls. Sex-specific changes in cellular and behavioral responses to fatty acid were observed in Adipor1 knockout mice. Linoleic acid (LA)-induced calcium responsiveness appears to be reduced in taste cells from Adipor1-deficient males and increased in taste cells from Adipor1-deficient females. Brief-access taste testing revealed a loss of fat taste behavioral responsiveness in naïve Adipor1 -/- animals. Fat taste loss found in Adipor1 -/- males was restored after fat exposure and showed no significant differences in taste behavioral responses to fatty acids with WT controls in two-bottle preference and conditioned taste aversion tests. Adipor1 -/- females were found to have diminished preference for LA in two-bottle preference tests, lower intralipid/water lick ratio in a brief-access assay, and reduced avoidance for LA in conditioned taste aversion assay. Furthermore, the taste nerve responses to intralipid and the dietary fat intakes appeared to be the same between Adipor1 -/- and WT mice. In the high-fat diet feeding study, Adipor1 -/- females gained more weight, while no differences in body weight gain were found in males. Together, we show that adiponectin/AdipoR1 signaling plays crucial sex-specific roles in the modulation of fat taste and the maintenance of healthy body weight primarily by regulating energy expenditure rather than dietary fat intake in mice.
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Affiliation(s)
- Fangjun Lin
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
- Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
| | - Timothy A. Gilbertson
- Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
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Cao H, Xu J, Wang H, Yi W, Yang D, Yang J, Sun J, Wang Y, Zhang F, Yan J, Li D. Fecal microbiota transplantation mitigates postdieting weight regain in mice by modulating the gut-liver axis. BMC Microbiol 2025; 25:135. [PMID: 40075266 PMCID: PMC11905490 DOI: 10.1186/s12866-025-03853-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 02/28/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Dysbiosis of the microbiome is strongly associated with weight rebound after dieting. However, the interactions between the host and microbiome and their relevance to the pathogenesis of post-diet weight rebound remain unclear. PURPOSE This study aimed to evaluate the effects of fecal microbiota transplantation (FMT) on post-diet weight regain and to investigate the underlying mechanisms by which FMT inhibits weight regain. METHODS FMT was administered once daily to mice for 5 weeks. Gas chromatography tandem mass spectrometry was employed to analyze short-chain fatty acid levels in serum, ultrahigh-performance liquid chromatography tandem mass spectrometry was utilized for analyzing hepatic lipid metabolites, and shotgun metagenomic sequencing was applied to examine the intestinal microbiome. RESULTS FMT reduced weight regain and prevented lipid accumulation in both liver and adipose tissue while also improving glucose intolerance in mice. Furthermore, FMT increased the abundance of Enterorhabdus caecimuris and decreased the abundances of Burkholderiales, Sutterellaceae, Turicimonas muris, Bacteroides stercorirosoris, and Acetivibrio ethanolgignens within the gut microbiota. Additionally, elevated propionic acid levels and significant alterations in hepatic lipid metabolites were observed following FMT administration. CONCLUSIONS Our findings demonstrate that FMT effectively mitigates post-diet weight regain and associated complications. These effects are mediated through interactions between the gut microbiota and the liver via the gut-propionic acid-liver axis. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Hong Cao
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Jiangwei Xu
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Han Wang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Wanya Yi
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Dandan Yang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Ju Yang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Jing Sun
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yingyu Wang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Feng Zhang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Institute of Future Food Technology, JITRI, Yixing, 214200, China
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Jiai Yan
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China.
- Wuxi School of Medicine, Jiangnan University, Wuxi, China.
- Institute of Future Food Technology, JITRI, Yixing, 214200, China.
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China.
| | - Dan Li
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China.
- Wuxi School of Medicine, Jiangnan University, Wuxi, China.
- Institute of Future Food Technology, JITRI, Yixing, 214200, China.
- Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, China.
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15
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Garbas K, Zapała Ł, Ślusarczyk A, Piekarczyk H, Piecha T, Radziszewski P. Beyond urodynamics: non-invasive approaches to diagnosing detrusor underactivity in men with lower urinary tract symptoms - a systematic review. BMC Urol 2025; 25:44. [PMID: 40050880 PMCID: PMC11887070 DOI: 10.1186/s12894-025-01722-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/20/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND To evaluate and synthesize existing evidence on non-invasive methods for diagnosing detrusor underactivity (DU) in men presenting with lower urinary tract symptoms (LUTS), focusing on their feasibility and diagnostic accuracy. METHODS A systematic search of PubMed, Scopus, and Web of Science databases was conducted for original articles reporting on non-invasive diagnostic tests for DU in men with LUTS. Data extraction focuses on study characteristics, diagnostic methods, and accuracy. The risk of bias was assessed using the QUADAS-2 tool. RESULTS Eighteen studies involving 7390 patients, of whom 3194 were diagnosed with DU, were included in our analysis. The evaluated diagnostic methods included ultrasound parameters, biomarkers, uroflowmetry results, symptom questionnaires, and clinical characteristics. Developed models, including those based on artificial intelligence (AI), and nomograms were also assessed. The symptom questionnaire DUA-SQ showed the highest sensitivity of 95.8%, while ultrasound measurements, such as detrusor wall thickness showed 100% specificity but limited sensitivity (42%). Models incorporating clinical variables achieved sensitivity rates of over 75%. Uroflowmetry parameters, particularly presence of "sawtooth" and "interrupted" waveforms, demonstrated sensitivity of 80% and specificity of 87%. Biomarkers, including serum adiponectin and urine NO/ATP ratio, achieved sensitivity of 79% and 88.5%, respectively. AI models showed potential, with sensitivities ranging from 65.9% to 79.7%. Due to the poor quality of the studies and data heterogeneity, meta-analysis was not performed. CONCLUSIONS Non-invasive diagnostic methods for DU, particularly DUA-SQ, ultrasound measurements, and AI models, demonstrate potential, though their accuracies vary. Further research is needed to standardize these methods and enhance their diagnostic reliability. TRIAL REGISTRATION The study protocol was registered with PROSPERO (CRD42024556425). CLINICAL TRIAL NUMBER not applicable.
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Affiliation(s)
- Karolina Garbas
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland.
| | - Łukasz Zapała
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland
| | - Aleksander Ślusarczyk
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland
| | - Hanna Piekarczyk
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland
| | - Tomasz Piecha
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland
| | - Piotr Radziszewski
- Department of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005, Warsaw, Poland
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Misra A, Kumar A, Kuchay MS, Ghosh A, Gulati S, Choudhary NS, Dutta D, Sharma P, Vikram NK. Consensus guidelines for the diagnosis and management of metabolic dysfunction-associated steatotic liver disease in adult Asian Indians with type 2 diabetes. Diabetes Metab Syndr 2025; 19:103209. [PMID: 40222341 DOI: 10.1016/j.dsx.2025.103209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/14/2025] [Accepted: 02/17/2025] [Indexed: 04/15/2025]
Affiliation(s)
- Anoop Misra
- Fortis CDOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India; Diabetes Foundation India, New Delhi, India.
| | - Ashish Kumar
- Gastroenterology & Hepatology,Sir Ganga Ram Hospital, Rajinder Nagar New Delhi, India
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta, The Medicity, Gurugram, 122001, Haryana, India
| | - Amerta Ghosh
- Fortis CDOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India
| | - Seema Gulati
- National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India; Diabetes Foundation India, New Delhi, India
| | | | - Deep Dutta
- Department of Endocrinology, Center for Endocrinology, Diabetes, Arthritis & Rheumatism (CEDAR) Super speciality Clinics, New Delhi, India
| | - Praveen Sharma
- Gastroenterology & Hepatology,Sir Ganga Ram Hospital, Rajinder Nagar New Delhi, India
| | - Naval K Vikram
- Department of Internal Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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17
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Miyake G, Nagasaka A, Bando Y, Sakiyama K, Iseki S, Sakashita H, Amano O. Expression and localization of adiponectin in myoepithelial cells in sublingual glands of normal and diabetic rats. J Oral Biosci 2025; 67:100590. [PMID: 39613095 DOI: 10.1016/j.job.2024.100590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 12/01/2024]
Abstract
OBJECTIVES Adiponectin is a hormone produced by adipocytes with anti-atherosclerotic and anti-diabetic properties. We previously discovered that adiponectin is specifically localized in the myoepithelial cells of rat sublingual glands. This study aims to investigate the localization of adiponectin and its receptors, AdipoR1 and AdipoR2, in adult rats, postnatally developing rats, and diabetic model rats. METHODS We examined the localization and expression of adiponectin and its receptors by immunohistochemistry and RT-PCR in the sublingual glands of adult rats and in two diabetic rat models: Streptozotocin (STZ)-treated rats for type 1 diabetes and GK rats for type 2 diabetes. RESULTS In rat sublingual glands, adiponectin was localized in the cytoplasm of myoepithelial cells, while AdipoR1 and AdipoR2 were localized in the basolateral membrane of mucous acinar cells. In GK rats, there was a significant decrease in the immunoreactivity and mRNA levels of adiponectin, while both AdipoR1 and AdipoR2 expression levels were upregulated. In STZ-treated rats, both adiponectin and its receptors showed reduced expression. CONCLUSIONS Adiponectin acts as a paracrine factor in sublingual myoepithelial cells, influencing salivary secretion through upregulated receptors in acinar cells, particularly in type 2 diabetes. This process is associated with a reduction in myoepithelial adiponectin levels.
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Affiliation(s)
- Genki Miyake
- Division of Histology, Meikai University School of Dentistry, Sakado, Saitama, Japan; Division of Oral and Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama, Japan
| | - Arata Nagasaka
- Division of Histology, Meikai University School of Dentistry, Sakado, Saitama, Japan
| | - Yasuhiko Bando
- Division of Histology, Meikai University School of Dentistry, Sakado, Saitama, Japan
| | - Koji Sakiyama
- Division of Anatomy, Meikai University School of Dentistry, Sakado, Saitama, Japan
| | - Shoichi Iseki
- Faculty of Health Sciences Department of Clinical Engineering, Komatsu University, Komatsu, Ishikawa, Japan
| | - Hideaki Sakashita
- Division of Oral and Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama, Japan; Department of Oral and Maxillofacial Surgery, Abiko Seijinkai Hospital, Abiko, Chiba, Japan
| | - Osamu Amano
- Division of Histology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
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18
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Jeong AY, Ma EB, Hong SJ, Kim E, Ko S, Huh JY, Kim YM. Kombucha inhibits adipogenesis and promotes lipolytic activity in 3T3-L1 adipocytes. Food Sci Biotechnol 2025; 34:1037-1043. [PMID: 39974855 PMCID: PMC11832843 DOI: 10.1007/s10068-024-01740-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/24/2024] [Accepted: 10/11/2024] [Indexed: 02/21/2025] Open
Abstract
This research was conducted to investigate the anti-obesity effects of black tea or green tea kombucha (BK, GK) and compared their compositional differences. As a result of kombucha treatment during the adipocyte differentiation process, peroxisome proliferator-activated receptor γ was significantly decreased, and CCAAT/enhancer binding protein α and adipocyte protein 2 showed a tendency to decrease with BK treatment. Oil red O staining results also demonstrated a reduction of lipid accumulation by BK treatment compared to the control. In mature adipocytes, BK significantly upregulated the gene expression of hormone-sensitive lipase and tended to increase the expression of adipose triglyceride lipase and adiponectin. Additionally, as a biomarker of lipolysis, glycerol content also marginally increased with either BK or GK treatment. The differences were observed in tea polyphenol compound and organic acid contents between BK and GK. In conclusion, these results suggest that black tea kombucha may have anti-obesity activity. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-024-01740-8.
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Affiliation(s)
- Ah-Young Jeong
- Jeollanamdo Agricultural Research and Extension Services, Jeollanamdo, 58213 Republic of Korea
- Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, 61186 Republic of Korea
| | - Eun-Bi Ma
- College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea
| | - Seong-Jin Hong
- Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, 61186 Republic of Korea
- Research Institute of Agricultural Science and Technology, Chonnam National University, Gwangju, 61186 Republic of Korea
| | - Eunhye Kim
- Jeollanamdo Agricultural Research and Extension Services, Jeollanamdo, 58213 Republic of Korea
| | - Sugju Ko
- Jeollanamdo Agricultural Research and Extension Services, Jeollanamdo, 58213 Republic of Korea
| | - Joo Young Huh
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
- Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Seoul, Republic of Korea
| | - Young-Min Kim
- Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, 61186 Republic of Korea
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Chen CL, Yang WS, Yang HI, Chen CF, Wang LY, Lu SN, Kao JH, Chen PJ, Chen CJ. Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study. Liver Cancer 2025; 14:19-35. [PMID: 40144469 PMCID: PMC11936446 DOI: 10.1159/000539909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/11/2024] [Indexed: 03/28/2025] Open
Abstract
Introduction Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. Methods Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. Results Among 3,931 HBsAg(+)/anti-HCV(-) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 105 IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55-3.28; OR = 2.11, 95% CI: 1.47-3.04; and OR = 1.92, 95% CI: 1.47-2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27-0.85), HBsAg (HR = 0.69, 95% CI: 0.49-0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43-0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98-4.20, HCC (HR = 2.38, 95% CI: 1.52-3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51-3.54). HBV genotype significantly modified the adiponectin-HCC (Pinteraction = 0.005) and adiponectin-liver death associations (Pinteraction = 0.0157), with higher risk among genotype C. Conclusion Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.
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Affiliation(s)
- Chi-Ling Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hwai-I. Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
- Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Chuen-Fei Chen
- Department of Medicine, Mackay Medical College, Kaohsiung, Taiwan
| | - Li-Yu Wang
- Department of Medicine, Mackay Medical College, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
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20
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Natarajan D, Ekambaram S, Tarantini S, Nagaraja RY, Yabluchanskiy A, Hedrick AF, Awasthi V, Subramanian M, Csiszar A, Balasubramanian P. Chronic β3 adrenergic agonist treatment improves neurovascular coupling responses, attenuates blood-brain barrier leakage and neuroinflammation, and enhances cognition in aged mice. Aging (Albany NY) 2025; 17:448-463. [PMID: 39976587 PMCID: PMC11892913 DOI: 10.18632/aging.206203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 01/29/2025] [Indexed: 02/26/2025]
Abstract
Microvascular endothelial dysfunction, characterized by impaired neurovascular coupling, reduced glucose uptake, blood-brain barrier disruption, and microvascular rarefaction, plays a critical role in the pathogenesis of age-related vascular cognitive impairment (VCI). Emerging evidence points to non-cell autonomous mechanisms mediated by adverse circulating milieu (an increased ratio of pro-geronic to anti-geronic circulating factors) in the pathogenesis of endothelial dysfunction leading to impaired cerebral blood flow and cognitive decline in the aging population. In particular, age-related adipose dysfunction contributes, at least in part, to an unfavorable systemic milieu characterized by chronic hyperglycemia, hyperinsulinemia, dyslipidemia, and altered adipokine profile, which together contribute to microvascular endothelial dysfunction. Hence, in the present study, we aimed to test whether thermogenic stimulation, an intervention known to improve adipose and systemic metabolism by increasing cellular energy expenditure, could mitigate brain endothelial dysfunction and improve cognition in the aging population. Eighteen-month-old C57BL/6J mice were treated with saline or β3-adrenergic agonist (CL 316, 243, CL) for 6 weeks followed by functional analysis to assess endothelial function and cognition. CL treatment improved neurovascular coupling responses and rescued brain glucose uptake in aged animals. In addition, CL treatment also attenuated blood-brain barrier leakage and associated neuroinflammation in the cortex and increased microvascular density in the hippocampus of aged mice. More importantly, these beneficial changes in microvascular function translated to improved cognitive performance in aged mice. Our results suggest that β3-adrenergic agonist treatment improves multiple aspects of cerebromicrovascular function and can be potentially repurposed for treating age-associated cognitive decline.
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Affiliation(s)
- Duraipandy Natarajan
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Shoba Ekambaram
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Stefano Tarantini
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Raghavendra Y. Nagaraja
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Andriy Yabluchanskiy
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Andria F. Hedrick
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Vibhudutta Awasthi
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Madhan Subramanian
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 73104, USA
| | - Anna Csiszar
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Priya Balasubramanian
- Department of Neurosurgery, Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- The Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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21
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Bernhardt SM, House CD. Bisphenol A and DDT disrupt adipocyte function in the mammary gland: implications for breast cancer risk and progression. Front Oncol 2025; 15:1490898. [PMID: 40034592 PMCID: PMC11873108 DOI: 10.3389/fonc.2025.1490898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 01/31/2025] [Indexed: 03/05/2025] Open
Abstract
As breast cancer incidence continues to rise worldwide, there is a pressing need to understand the environmental factors that contribute to its development. Obesogens, including Bisphenol A (BPA) and Dichlorodiphenyltrichloroethane (DDT), are highly prevalent in the environment, and have been associated with obesity and metabolic dysregulation. BPA and DDT, known to disrupt hormone signaling in breast epithelial cells, also promote adipogenesis, lipogenesis, and adipokine secretion in adipose tissue, directly contributing to the pathogenesis of obesity. While the adipose-rich mammary gland may be particularly vulnerable to environmental obesogens, there is a scarcity of research investigating obesogen-mediated changes in adipocytes that drive oncogenic transformation of breast epithelial cells. Here, we review the preclinical and clinical evidence linking BPA and DDT to impaired mammary gland development and breast cancer risk. We discuss how the obesogen-driven mechanisms that contribute to obesity, including changes in adipogenesis, lipogenesis, and adipokine secretion, could provide a pro-inflammatory, nutrient-rich environment that promotes activation of oncogenic pathways in breast epithelial cells. Understanding the role of obesogens in breast cancer risk and progression is essential for informing public health guidelines aimed at minimizing obesogen exposure, to ultimately reduce breast cancer incidence and improve outcomes for women.
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Affiliation(s)
- Sarah M. Bernhardt
- Department of Biology, San Diego State University, San Diego, CA, United States
| | - Carrie D. House
- Department of Biology, San Diego State University, San Diego, CA, United States
- Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States
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22
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Si S, Zhang X, Yu Y, Zhong X, Zhang X, Yuan J, Chu KH, Li F. Molecular mechanisms of Mmd2 gene in regulating growth of the Pacific white shrimp Litopenaeus vannamei. MARINE LIFE SCIENCE & TECHNOLOGY 2025; 7:50-65. [PMID: 40027329 PMCID: PMC11871217 DOI: 10.1007/s42995-024-00273-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 11/28/2024] [Indexed: 03/05/2025]
Abstract
Growth of the Pacific white shrimp Litopenaeus vannamei, the most important farmed crustacean, has consistently been a focal point for breeders. Over the past decades, some candidate genes for shrimp growth have been identified. However, further research is needed to elucidate the molecular regulatory mechanism of these genes. LvMmd2 was previously identified as a candidate gene that may inhibit the growth of L. vannamei. In this study, we analyzed the genotype and expression of the LvMmd2 gene in a breeding family and indicated its role as a growth-inhibiting gene. We found that LvMmd2 co-localized with its homolog LvPAQR3 at the Golgi apparatus. Using co-immunoprecipitation (Co-IP) and DUAL membrane system yeast two-hybrid (MbY2H), we indicated the interactions between LvMmd2 and LvPAQR3, LvPAQR3 and LvRaf1, as well as LvMmd2 and LvRho. These results suggest that LvMmd2 directly and indirectly regulates the Ras signaling pathway. Furthermore, we show that the LvMmd2 gene may indirectly affect the PI3K/AKT, insulin, and Hippo signaling pathways to regulate cell proliferation and differentiation via LvPAQR3 and LvRaf1. Through transcriptome and MbY2H analyses, we have also revealed the interaction between LvMmd2 and proteins involved in growth, immunity, protein transport, synthesis, and modification. These findings demonstrate the various molecular pathways through which LvMmd2 regulates L. vannamei growth. This study provides insights into the mechanism of shrimp growth regulated by Mmd2, enhances our understanding of LvMmd2 function, and highlights its potential application in shrimp breeding. Supplementary Information The online version contains supplementary material available at 10.1007/s42995-024-00273-7.
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Affiliation(s)
- Shuqing Si
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
| | - Xiaojun Zhang
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
| | - Yang Yu
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Chinese Academy of Sciences, Wuhan, 430072 China
| | - Xiaoyun Zhong
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
| | - Xiaoxi Zhang
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
| | - Jianbo Yuan
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
| | - Ka Hou Chu
- Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 510301 China
- School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong China
| | - Fuhua Li
- CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071 China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266237 China
- College of Earth Science, University of Chinese Academy of Sciences, Beijing, 100049 China
- Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Chinese Academy of Sciences, Wuhan, 430072 China
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23
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Moreira RJ, Oliveira PF, Spadella MA, Ferreira R, Alves MG. Do Lifestyle Interventions Mitigate the Oxidative Damage and Inflammation Induced by Obesity in the Testis? Antioxidants (Basel) 2025; 14:150. [PMID: 40002337 PMCID: PMC11851673 DOI: 10.3390/antiox14020150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/18/2025] [Accepted: 01/23/2025] [Indexed: 02/27/2025] Open
Abstract
Obesity results from a disproportionate accumulation of fat and has become a global health concern. The increase in adipose tissue is responsible for several systemic and testicular changes including hormone levels (leptin, adiponectin, testosterone, estrogen), inflammatory cytokines (increase in TNF-α and IL-6 and decrease in IL-10), and redox state (increase in reactive oxygen species and reduction in antioxidant enzymes). This results in poor sperm quality and compromised fertility in men with obesity. Lifestyle modifications, particularly diet transition to caloric restriction and physical exercise, are reported to reverse these negative effects. Nevertheless, precise mechanisms mediating these benefits, including how they modulate testicular oxidative stress, inflammation, and metabolism, remain to be fully elucidated. The main pathway described by which these lifestyle interventions reverse obesity-induced oxidative damage is the Nrf2-SIRT1 axis, which modulates the overexpression of antioxidant defenses. Of note, some of the detrimental effects of obesity on the testis are inherited by the descendants of individuals with obesity, and while caloric restriction reverses some of these effects, no significant work has been carried out regarding physical exercise. This review discusses the consequences of obesity-induced testicular oxidative stress on adult and pediatric populations, emphasizing the therapeutic potential of lifestyle to mitigate these detrimental effects.
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Affiliation(s)
- Ruben J. Moreira
- Institute of Biomedicine, Department of Medical Sciences (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal;
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (P.F.O.); (R.F.)
| | - Pedro F. Oliveira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (P.F.O.); (R.F.)
| | | | - Rita Ferreira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; (P.F.O.); (R.F.)
| | - Marco G. Alves
- Institute of Biomedicine, Department of Medical Sciences (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal;
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Anwar C, Chu YC, Tsai ML, Ho CT, Lai CS. Tetrahydrocurcumin alleviates di-(2-ethylhexyl) phthalate-induced adipose tissue dysfunction and testicular toxicity in adult mice: possible involvement of adiponectin-adipoR signaling in the testis. Food Funct 2025; 16:583-600. [PMID: 39704213 DOI: 10.1039/d4fo04271a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
Widespread exposure to endocrine disruptors is associated with metabolic dysfunction and reproductive toxicity. Tetrahydrocurcumin (THC) has attracted attention as it offers protection against obesity and metabolic disorders due to its potent antioxidative and diverse biological properties but its influence and underlying mechanism of action on adipose tissue function and DEHP-induced testicular injury remain unknown. Our results showed that THC (100 mg kg-1 day-1) administration for 27 weeks enlarged adipocytes while attenuating macrophage infiltration and IL-6 expression in the adipose tissue of male C57BL/6J mice exposed to 5 mg kg-1 day-1 of DEHP. Moreover, THC ameliorated DEHP-induced deregulation of adiponectin but not leptin. DEHP caused testicular histological damage, spermatogenesis impairment, apoptosis, inflammation, and AGE, which were improved by THC. THC treatment elevated Nrf2/HO-1 and decreased Glut1 in interstitial Leydig cells, which may contribute to its beneficial effects on the testis. Our results further demonstrated that THC also ameliorated circulating adiponectin and testicular adipoR1-AMPK signaling, partially accounting for the improvement of DEHP-caused testicular dysfunction. The finding of this study revealed that THC is a promising candidate for improving adipose and testicular dysfunction caused by DEHP.
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Affiliation(s)
- Choirul Anwar
- Institute of Aquatic Science and Technology, Collage of Hydrosphere Science, National Kaohsiung University of Science and Technology, No. 142, Haijhuan Rd., Nanzih Dist., Kaohsiung City 81157, Taiwan
| | - Yu-Chi Chu
- Department of Seafood Science, National Kaohsiung University of Science and Technology, No. 142, Haijhuan Rd., Nanzih Dist., Kaohsiung City 81157, Taiwan.
| | - Mei-Ling Tsai
- Department of Seafood Science, National Kaohsiung University of Science and Technology, No. 142, Haijhuan Rd., Nanzih Dist., Kaohsiung City 81157, Taiwan.
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA
| | - Ching-Shu Lai
- Department of Seafood Science, National Kaohsiung University of Science and Technology, No. 142, Haijhuan Rd., Nanzih Dist., Kaohsiung City 81157, Taiwan.
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25
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Lin J, Liang Z, Liang Y, Cao X, Tang X, Zhuang H, Yin X, Zhao D, Shen L. A systematically investigation of plasma complement and coagulation-related proteins and adiponectin in gestational diabetes mellitus by multiple reaction monitoring technology. Acta Diabetol 2025:10.1007/s00592-025-02451-0. [PMID: 39821309 DOI: 10.1007/s00592-025-02451-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 01/05/2025] [Indexed: 01/19/2025]
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is defined as a glucose intolerance resulting in hyperglycaemia of variable severity with onset during pregnancy, and is prevalent worldwide. The study of diagnostic markers of GDM in early pregnancy is important for early diagnosis and early intervention of GDM. The aim of this study was to search for biomarkers of GDM in early and mid-pregnancy using a targeted proteomics approach. METHODS Through multiple response monitoring (MRM) technology and bioinformatics analysis including machine learning, 44 proteins associated with complement and coagulation cascades, and one protein, adiponectin, which is frequently reported to be associated with GDM, were targeted for quantitative analysis, and potential biomarkers were screened. RESULTS The results showed that 7 and 6 proteins were identified as differentially expressed proteins (DEPs) between pregnant women subsequently diagnosed with GDM and controls during the first trimester, as well as between GDM cases and controls during the second trimester, respectively. Among them, C1QC and CFHR1 may serve as early predictive markers, and C1QC and adiponectin may serve as mid-term diagnostic markers. DISCUSSION Complement and coagulation-related proteins and adiponectin, have been implicated in the pathogenesis of GDM, and some of these proteins have the potential to serve as markers for the prediction or diagnosis of GDM.
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Affiliation(s)
- Jing Lin
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Zhiyuan Liang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Yi Liang
- Department of Clinical Nutrition, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China
| | - Xueshan Cao
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Xiaoxiao Tang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Hongbin Zhuang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Xiaoping Yin
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, P. R. China
| | - Danqing Zhao
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, P. R. China.
| | - Liming Shen
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China.
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, P. R. China.
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26
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Selvaraju V, Babu SR, Judd RL, Geetha T. Lupeol Attenuates Palmitate-Induced Hypertrophy in 3T3-L1 Adipocytes. Biomolecules 2025; 15:129. [PMID: 39858523 PMCID: PMC11763665 DOI: 10.3390/biom15010129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/11/2025] [Accepted: 01/13/2025] [Indexed: 01/30/2025] Open
Abstract
Obesity is characterized by the enlargement of adipose tissue due to an increased calorie intake exceeding the body's energy expenditure. Changes in the size of adipose tissue can lead to harmful consequences, with excessive fat accumulation resulting in adipocyte hypertrophy and promoting metabolic dysfunction. These adiposity-associated pathologies can be influenced by dietary components and their potential health benefits. Lupeol, a pharmacologically active pentacyclic triterpenoid found in medicinal plants, vegetables, and fruits, has been shown to exhibit antioxidant and anti-inflammatory properties. This study investigated the role of lupeol on adipocyte hypertrophy by evaluating key adipogenic regulators in vitro. First, 3T3-L1 MBX mouse embryonic cells were differentiated into adipocytes and hypertrophy was induced using 500 µM palmitic acid. The treated adipocytes showed a significantly increased lipid droplet size, confirming adipocyte hypertrophy. Both adipocytes and hypertrophied adipocytes were then treated with or without 60 µM lupeol, following a dose-dependent study. Lipid droplet size was assessed and validated by Oil Red O staining. Western blot analysis was performed to measure the expression of adipogenic and inflammatory markers. Differentiated adipocytes showed increased fatty acid-binding protein 4 (FABP4) expression and Oil Red O staining, indicating an increased lipid content. Western blot analysis revealed that lupeol treatment reduced the expression of FABP4, peroxisome proliferator-activated receptor-γ (PPARγ), and adipokines. In conclusion, the results suggest that lupeol reverts the inflammatory and adipogenic markers that are enhanced in adipocyte hypertrophy. Through its anti-inflammatory effects, lupeol offers protective effects against adipocyte hypertrophy and contributes to reducing hypertrophic adiposity.
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Affiliation(s)
| | - Shivani R. Babu
- Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA
| | - Robert L. Judd
- Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL 36849, USA
| | - Thangiah Geetha
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
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27
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Guo Y, Zhao Y, Wei Z, Cao J. Effects of exogenous insulin supplementation on lipid metabolism in peripartum obese dairy cows. Front Vet Sci 2025; 11:1468779. [PMID: 39881718 PMCID: PMC11774932 DOI: 10.3389/fvets.2024.1468779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/24/2024] [Indexed: 01/31/2025] Open
Abstract
Cows with high body condition scores experience more severe negative energy balance (NEB) and undergo mobilization of more body fat during the peripartum period, leading to more production of nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA). Postpartum insulin secretion is lower, and insulin resistance is stronger in obese cows. Exogenous insulin supplementation has been hypothesized as a key approach for regulating NEFA in these cows. In this study, we assessed the effects of exogenous insulin supplementation on lipid metabolism, key genes regulated by insulin, and the underlying regulatory mechanism. We selected 181 periparturient multiparous obese dairy cows for the study. Cows in the insulin group (n = 96) received subcutaneous injections of 200 IU insulin (5 mL) on postpartum days 1 and 7, while cows in the control group (n = 85) received subcutaneous injections of 5 mL physiological saline on the same days. The incidence of ketosis was recorded and compared between the two groups. The results demonstrated that postpartum insulin injections significantly reduced the incidence of type II ketosis and delayed the onset time. Meanwhile, a cohort experiment was conducted on 20 cows selected from 181 field trial cows, with 10 cows in the insulin group and 10 cows in the control group. Blood samples were collected for biochemical indicators and subcutaneous adipose tissue was collected for paraffin-embedding and sectioning and RNA sequencing analysis. The results showed that insulin supplementation postpartum reduced concentrations of NEFA and BHBA as well as BCS loss, but did not affect glucose. Additionally, the expression of SREBF1 in insulin signaling pathway and the downstream-regulated lipogenesis network genes were successfully upregulated in insulin-treated healthy group. High expression of SREBF1 may be a key for postpartum insulin supplementation to improve insulin resistance, significantly reduce NEFA concentrations, and prevent or treat ketosis and fatty liver in obese cows. Postpartum administration of insulin could effectively decrease alterations of adipocytes size, which also fully validates that postpartum insulin supplementation promotes lipogenesis and reduces NEFA release.
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Affiliation(s)
| | | | | | - Jie Cao
- College of Veterinary Medicine, China Agricultural University, Beijing, China
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Wang L, Li J, Tang P, Zhu D, Tai L, Wang Y, Miyata T, Woodgett JR, Di LJ. GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders. Circ Res 2025; 136:91-111. [PMID: 39629559 DOI: 10.1161/circresaha.124.325187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 11/18/2024] [Accepted: 11/20/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported. METHODS GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3βADKO and GSK3αADKO). A comprehensive whole-body metabolism analysis was performed on obese GSK3βADKO mice induced by a high-fat diet. RNA sequencing was conducted on AT of both obese GSK3βADKO and GSK3αADKO mice. Various analyses, including vessel perfusion studies, lipolysis analysis, multiplex protein assays, in vitro protein phosphorylation assays, and whole-mount histology staining, were performed on AT of obese GSK3βADKO mice. Tube-formation experiments were performed using 3B-11 endothelial cells cultured in the conditional medium of matured adipocytes under hypoxic conditions. Chromatin precipitation and immunofluorescence studies were conducted using cultured adipocytes with GSK3 inhibition. RESULTS Our findings provide the first evidence that adipocyte-specific knockout of GSK3β expands AT vascularization and mitigates obesity-related metabolic disorders. GSK3β deficiency, but not GSK3α, in adipocytes activates AMPK (AMP-activated protein kinase), leading to increased phosphorylation and nuclear accumulation of HIF-2α, resulting in enhanced transcriptional regulation. Consequently, adipocytes increased VEGF (vascular endothelial growth factor) expression, which engages VEGFR2 on endothelial cells, promoting angiogenesis, expanding the vasculature, and improving vessel perfusion within obese AT. GSK3β deficiency promotes AT remodeling, shifting unhealthy adipocyte function toward a healthier state by increasing insulin-sensitizing hormone adiponectin and preserving healthy adipocyte function. These effects lead to reduced fibrosis, reactive oxygen species, and ER (endoplasmic reticulum) stress in obese AT and improve metabolic disorders associated with obesity. CONCLUSIONS Deletion of GSK3β in adipocytes activates the AMPK/HIF-2α/VEGF/VEGFR2 axis, promoting vasculature expansion within obese AT. This results in a significantly improved local microenvironment, reducing inflammation and effectively ameliorating metabolic disorders associated with obesity.
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Affiliation(s)
- Li Wang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
- The Ministry of Education Frontiers Science Center for Precision Oncology (L.W., L.D.), University of Macau, China
- Proteomics, Metabolomics and Drug development core facility, Faculty of Health Sciences (L.W.), University of Macau, China
| | - Jiajia Li
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Ping Tang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Dongliang Zhu
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Lixin Tai
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Yuan Wang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Tsukiko Miyata
- Lunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.)
| | - James R Woodgett
- Lunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.)
| | - Li-Jun Di
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
- The Ministry of Education Frontiers Science Center for Precision Oncology (L.W., L.D.), University of Macau, China
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Wang L, Wang S, Anema JA, Moghaddam VA, Lu Y, Lin S, Daw EW, Kuipers AL, Miljkovic I, Brent M, Patti GJ, Thygarajan B, Zmuda JM, Province MA, An P. Novel loci for triglyceride/HDL-C ratio longitudinal change among subjects without T2D. J Lipid Res 2025; 66:100702. [PMID: 39557295 PMCID: PMC11699370 DOI: 10.1016/j.jlr.2024.100702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/23/2024] [Accepted: 11/12/2024] [Indexed: 11/20/2024] Open
Abstract
Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the LPL (P = 1.58e-9) for ΔTHR; this locus has been reported before influencing baseline THR levels. Our GWLS found significant linkage with a logarithm of the odds exceeding 3 on 3q28 (logarithm of the odds = 4.1). Using a subset of 25 linkage-enriched families, we assessed sequence elements under 3q28 and identified two novel variants (EIF4A2 [eukaryotic translation initiation factor 4A2]/ADIPOQ-rs114108468, p = 5e-6, minor allele frequency = 1.8%; TPRG1-rs16864075, p = 3e-6, minor allele frequency = 8%; accounted for ∼28% and ∼29% of the linkage, respectively). While the former variant was associated with EIF4A2 (p = 7e-5)/ADIPOQ (P = 3.49e-2) transcriptional levels, the latter variant was not associated with TPRG1 (P = 0.23) transcriptional levels. Replication in the Framingham Heart Study Offspring Cohort observed modest effect of these loci on ΔTHR. Our approach discovered two novel gene variants EIF4A2/ADIPOQ-rs114108468 and TPRG1-rs16864075 on 3q28 for ΔTHR among subjects without diabetes. Our findings provided novel insights into the molecular regulation of insulin resistance.
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Affiliation(s)
- Lihua Wang
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA.
| | - Siyu Wang
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Jason A Anema
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Vaha A Moghaddam
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Yanli Lu
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Shiow Lin
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - E Warwick Daw
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Allison L Kuipers
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Iva Miljkovic
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Michael Brent
- Division of Computation & Data Sciences, Washington University School of Medicine, St. Louis, MO, USA
| | - Gary J Patti
- Department of Chemistry, Washington University School of Medicine, St. Louis, MO, USA
| | - Bharat Thygarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Joseph M Zmuda
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Michael A Province
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
| | - Ping An
- Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
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30
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Park H, Trupiano SP, Medarev SL, Ghosh P, Caldwell JT, Yarrow JF, Muller-Delp JM. Aerobic exercise training-induced bone and vascular adaptations in mice lacking adiponectin. Bone 2025; 190:117272. [PMID: 39369833 PMCID: PMC11795456 DOI: 10.1016/j.bone.2024.117272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/23/2024] [Accepted: 10/03/2024] [Indexed: 10/08/2024]
Abstract
Adiponectin regulates lipid and glucose metabolism, and insulin sensitivity in various target organs; however, the effects of adiponectin on bone health remain controversial. Exercise training can enhance bone density, bone microarchitecture, and blood flow. This study aimed to elucidate the role of adiponectin in adaptations of bone microarchitecture and bone vasculature in response to aerobic exercise training. Adult male C57BL/6 wild-type (WT) and homozygous adiponectin knockout (AdipoKO) mice were either treadmill exercise trained or remained sedentary for 8-10 weeks. The trabecular structures of the distal femoral metaphysis, a weight-bearing bone, and the mandible, a non-weight-bearing bone, were examined using microcomputed tomography. The femoral principal nutrient arteries were isolated to assess vasoreactivity (vasodilation and vasoconstriction) and structural remodeling. At the femoral metaphysis, impaired trabecular bone structures, including reduced connectivity density and increased trabecular spacing, were observed in AdipoKO mice compared to WT mice. In addition, nitric oxide-mediated, endothelium-dependent vasodilation was substantially reduced, and wall-to-lumen ratio was significantly increased in the femoral principal nutrient artery of AdipoKO mice. Interestingly, although exercise training-induced enhancements in trabecular connectivity density were observed at the femoral metaphysis of both WT and AdipoKO, increased vasoconstrictor responses were only observed in the femoral principal nutrient artery of WT mice, not in the AdipoKO mice. In mandibular trabecular bone, exercise training increased trabecular bone volume fraction (BV/TV, %) and intersection surface in the mandible of both WT and AdipoKO mice. These findings indicate that adiponectin is crucial for maintaining normal bone microarchitecture and vasculature. Although the absence of adiponectin compromises bone vascular adaptation to exercise training in mice, some exercise training-induced alterations in bone microarchitecture occurred in the absence of adiponectin, suggesting contribution of compensatory mechanisms during exercise training.
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Affiliation(s)
- Hyerim Park
- Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, USA
| | - Samuel P Trupiano
- Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA
| | - Steven L Medarev
- Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA
| | - Payal Ghosh
- Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, USA
| | - Jacob T Caldwell
- Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA; Department of Exercise and Sport Science, University of Wisconsin-La Crosse, La Crosse, WI, USA
| | - Joshua F Yarrow
- Eastern Colorado Geriatrics Research, Education, and Clinical Center, Rocky Mountain Regional Veterans Affairs Medical Center, VA Eastern Colorado Health Care System, Aurora, CO, USA
| | - Judy M Muller-Delp
- Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
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31
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Wang T, Zhou D, Hong Z. Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2025; 6:e70030. [PMID: 39764565 PMCID: PMC11702502 DOI: 10.1002/mco2.70030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/11/2024] [Accepted: 11/12/2024] [Indexed: 03/17/2025] Open
Abstract
Sarcopenia is defined as a muscle-wasting syndrome that occurs with accelerated aging, while cachexia is a severe wasting syndrome associated with conditions such as cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. Sarcopenia can be considered a component of cachexia, with the bidirectional interplay between adipose tissue and skeletal muscle potentially serving as a molecular mechanism for both conditions. However, the underlying mechanisms differ. Recognizing the interplay and distinctions between these disorders is essential for advancing both basic and translational research in this area, enhancing diagnostic accuracy and ultimately achieving effective therapeutic solutions for affected patients. This review discusses the muscle microenvironment's changes contributing to these conditions, recent therapeutic approaches like lifestyle modifications, small molecules, and nutritional interventions, and emerging strategies such as gene editing, stem cell therapy, and gut microbiome modulation. We also address the challenges and opportunities of multimodal interventions, aiming to provide insights into the pathogenesis and molecular mechanisms of sarcopenia and cachexia, ultimately aiding in innovative strategy development and improved treatments.
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Affiliation(s)
- Tiantian Wang
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Dong Zhou
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Zhen Hong
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
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32
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Duan F, Wu J, Chang J, Peng H, Liu Z, Liu P, Han X, Sun T, Shang D, Yang Y, Li Z, Li P, Liu Y, Zhu Y, Lv Y, Guo X, Zhao Y, An Y. Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction. Differentiation 2025; 141:100832. [PMID: 39709882 DOI: 10.1016/j.diff.2024.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.
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Affiliation(s)
- Feiyi Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiaoyan Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiayi Chang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Haoyuan Peng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zitao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengfei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Xu Han
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Tiantian Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Dandan Shang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yutian Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yixuan Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yonghao Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yunzhi Lv
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Xiumei Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Ying Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China.
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Chen K, Qin YR, Liu SQ, Chen RL. Remission of iron overload in adipose tissue of obese mice by fatty acid-modified polyoxovanadates. RARE METALS 2025; 44:461-471. [DOI: 10.1007/s12598-024-02925-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 09/11/2024]
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Shimizu R, Suzuki H, Amitani M, Amitani H. The Effects of Yoga on Key Adipocytokines in Obesity: A Narrative Review of Leptin and Adiponectin. Cureus 2025; 17:e76792. [PMID: 39897330 PMCID: PMC11786781 DOI: 10.7759/cureus.76792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/31/2024] [Indexed: 02/04/2025] Open
Abstract
Obesity is a global health concern that increases the risk of numerous complications, including type 2 diabetes, hypertension, and cardiovascular diseases. Conventional obesity treatments, such as lifestyle modifications, pharmacotherapy, and surgical interventions, are often insufficient, highlighting the need for more efficient and effective approaches. Yoga, an ancient mind-body practice incorporating physical postures (asanas), breathing exercises (pranayama), and meditation, has emerged as a potential therapeutic intervention for obesity management. This review examines the functions of leptin and adiponectin, two key adipocytokines central to obesity, and evaluates the impact of yoga on these hormones. A literature search was conducted using PubMed, Scopus, and Google Scholar with the keywords "yoga" and "adipocytokine" as of May 5, 2024, resulting in the selection of 12 relevant studies. The majority of studies reviewed demonstrated that yoga significantly decreases leptin levels and increases adiponectin levels. Intensive yoga sessions and combined dietary interventions were found to contribute notably to improvements in these hormonal levels. These findings suggest that yoga may improve the balance between leptin and adiponectin, offering beneficial effects on anti-obesity and chronic inflammation reduction. Yoga, as an economical and non-invasive treatment option, presents a promising approach to managing obesity. Further research is expected to elucidate the underlying mechanisms and explore potential clinical applications.
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Affiliation(s)
- Rinne Shimizu
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JPN
- Kampo Medical Center, Kagoshima University Hospital, Kagoshima, JPN
- Department of General Medicine, Ryokusenkai Yonemori Hospital, Kagoshima, JPN
| | - Hajime Suzuki
- Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JPN
| | - Marie Amitani
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JPN
| | - Haruka Amitani
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JPN
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35
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Du YZ, Hu HJ, Yang JQ, Yuan Q, Huang R, Dong QX, Guo B, Cao Y, Guo J. The relationship between increased regional body fat and overactive bladder: a population-based study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:226. [PMID: 39719652 DOI: 10.1186/s41043-024-00725-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 12/18/2024] [Indexed: 12/26/2024]
Abstract
BACKGROUND The link between regional body fat distribution and overactive bladder (OAB) in prior epidemiological research has been uncertain. Our objective is to assess the relationship between increased regional body fat and the prevalence of OAB. METHODS Within this analysis, 8,084 individuals aged 20 years and older were selected from NHANES surveys conducted from 2011 to 2018. The evaluation of OAB symptoms utilized the overactive bladder symptom score (OABSS). Fat mass (FM) across various regions was quantified employing dual-energy X-ray absorptiometry, which assessed total FM, trunk FM, arm FM, and leg FM. The fat mass index (FMI) was calculated as the ratio of fat mass (kg) to the square of height (meters). Data weighting was performed in accordance with analysis guidelines. A linear logistic regression model was employed to assess the correlation between regional FMI and the occurrence of OAB. Stratified analyses were also conducted. RESULTS The study found significant associations between total FMI and limb FMI with OAB. After adjusting for all variables in the analysis, higher total FMI (OR = 1.07, 95% CI = 1.02-1.12) was linked to an increased risk of OAB. Trunk FMI (OR = 1.12, 95% CI = 1.03-1.22), arm FMI (OR = 1.59, 95% CI = 1.20-2.10), and leg FMI (OR = 1.12, 95% CI = 1.01-1.25) demonstrated significant correlations with OAB. The weighted associations between total FMI and limb FMI with OAB incidence showed no significant differences among most subgroups. CONCLUSIONS The data indicates a correlation between higher regional FMI and increased OAB risk across different populations.
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Affiliation(s)
- Yuan-Zhuo Du
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China
| | - Hong-Ji Hu
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China
| | - Jia-Qing Yang
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China
| | - Qian Yuan
- Nursing Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Rong Huang
- Nursing Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qian-Xi Dong
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China
| | - Biao Guo
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China
| | - Ying Cao
- Nursing Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
| | - Ju Guo
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China.
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Wat LW, Svensson KJ. Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases. Diabetologia 2024; 67:2626-2636. [PMID: 39180580 DOI: 10.1007/s00125-024-06253-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/01/2024] [Indexed: 08/26/2024]
Abstract
The tight regulation of glucose and lipid metabolism is crucial for maintaining metabolic health. Dysregulation of these processes can lead to the development of metabolic diseases. Secreted factors, or hormones, play an essential role in the regulation of glucose and lipid metabolism, thus also playing an important role in the development of metabolic diseases such as type 2 diabetes and obesity. Given the important roles of secreted factors, there has been significant interest in identifying new secreted factors and new functions for existing secreted factors that control glucose and lipid metabolism. In this review, we evaluate novel secreted factors or novel functions of existing factors that regulate glucose and lipid metabolism discovered in the last decade, including secreted isoform of endoplasmic reticulum membrane complex subunit 10, vimentin, cartilage intermediate layer protein 2, isthmin-1, lipocalin-2, neuregulin-1 and neuregulin-4. We discuss their discovery, tissues of origin, mechanisms of action and sex differences, emphasising their potential to regulate metabolic processes central to diabetes. Additionally, we discuss the translational barriers, particularly the absence of identified receptors, that hamper their functional characterisation and further therapeutic development. Ultimately, the identification of new secreted factors may give insights into previously unidentified pathways of disease progression and mechanisms of glucose and lipid homeostasis.
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Affiliation(s)
- Lianna W Wat
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - Katrin J Svensson
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
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Lee EO, Jin H, Kim S, Joo HK, Lee YR, An SY, Piao S, Lee KH, Jeon BH. Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice. Endocrinol Metab (Seoul) 2024; 39:932-945. [PMID: 39566547 PMCID: PMC11695485 DOI: 10.3803/enm.2024.2061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/29/2024] [Accepted: 08/19/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGRUOUND The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. METHODS APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. RESULTS APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. CONCLUSION APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.
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Affiliation(s)
- Eun-Ok Lee
- Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Hao Jin
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Sungmin Kim
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
| | - Hee Kyoung Joo
- Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Yu Ran Lee
- Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Soo Yeon An
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shuyu Piao
- Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Kwon Ho Lee
- Department of Physical Therapy, Joongbu University, Geumsan, Korea
| | - Byeong Hwa Jeon
- Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
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Yaqoob MU, Qi Y, Hou J, Zhe L, Zhu X, Wu P, Li Z, Wang M, Li Y, Yue M. Coated cysteamine and choline chloride could be potential feed additives to mitigate the harmful effects of fatty liver hemorrhagic syndrome in laying hens caused by high-energy low-protein diet. Poult Sci 2024; 103:104296. [PMID: 39305615 PMCID: PMC11437759 DOI: 10.1016/j.psj.2024.104296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/30/2024] [Accepted: 08/31/2024] [Indexed: 10/01/2024] Open
Abstract
The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.
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Affiliation(s)
- Muhammad Umar Yaqoob
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Yingying Qi
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Jia Hou
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Li Zhe
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Xiangde Zhu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Peng Wu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Zhefeng Li
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Minqi Wang
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Yan Li
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Min Yue
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
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Liu Y, Fu X, Sun J, Cui R, Yang W. AdipoRon exerts an antidepressant effect by inhibiting NLRP3 inflammasome activation in microglia via promoting mitophagy. Int Immunopharmacol 2024; 141:113011. [PMID: 39213872 DOI: 10.1016/j.intimp.2024.113011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
Depression is a serious mental disorder that threatens patients' physical and mental health worldwide. The activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is essential for microglia-mediated neuroinflammation and neuronal damage in depression. Numerous pathophysiological factors, such as mitochondrial dysfunction and impaired mitophagy, have an essential role in activating the NLRP3 inflammasome. AdipoRon is a potent adiponectin receptor agonist; however, its antidepressant effects have not been thoroughly investigated. In this study, we found that AdipoRon ameliorated depression-like behavior and neuronal damage induced by chronic unpredictable mild stress (CUMS). Further research demonstrated that AdipoRon inhibited the activation of the NLRP3 inflammasome and protected hippocampal neurons from microglial cytotoxicity by promoting mitophagy, increasing the clearance of damaged mitochondria, and reducing mtROS accumulation. Importantly, inhibition of mitophagy attenuated the antidepressant and neuroprotective effects of AdipoRon. Overall, these findings indicate that AdipoRon alleviates depression by inhibiting NLRP3 inflammasome activation in microglia via improving mitophagy.
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Affiliation(s)
- Yaqi Liu
- Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Xiying Fu
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Department of Endocrinology, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Jiangjin Sun
- Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Ranji Cui
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
| | - Wei Yang
- Department of Neurology, The Second Hospital of Jilin University, Changchun, Jilin Province, China; Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
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Carpi S, Daniele S, de Almeida JFM, Gabbia D. Recent Advances in miRNA-Based Therapy for MASLD/MASH and MASH-Associated HCC. Int J Mol Sci 2024; 25:12229. [PMID: 39596297 PMCID: PMC11595301 DOI: 10.3390/ijms252212229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern worldwide, affecting more than 1 billion adults. It may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and ultimately hepatocellular carcinoma (HCC). Emerging evidence has demonstrated the role in this transition of microRNAs (miRNAs), which regulate the expression of genes associated with lipid metabolism, inflammation, fibrosis, and cell proliferation. Specific miRNAs have been identified to exacerbate or mitigate fibrotic and carcinogenic processes in hepatic cells. The modulation of these miRNAs through synthetic mimics or inhibitors represents a promising therapeutic strategy. Preclinical models have demonstrated that miRNA-based therapies can attenuate liver inflammation, reduce fibrosis, and inhibit tumorigenesis, thus delaying or preventing the onset of HCC. However, challenges such as delivery mechanisms, off-target effects, and long-term safety remain to be addressed. This review, focusing on recently published preclinical and clinical studies, explores the pharmacological potential of miRNA-based interventions to prevent MASLD/MASH and progression toward HCC.
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Affiliation(s)
- Sara Carpi
- Department of Health Sciences, University ‘Magna Græcia’ of Catanzaro, 88100 Catanzaro, Italy
- NEST (National Enterprise for nanoScience and nanoTechnology), Istituto Nanoscienze-CNR and Scuola Normale Superiore, 41125 Modena, Italy
| | - Simona Daniele
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy; (S.D.); (J.F.M.d.A.)
| | | | - Daniela Gabbia
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
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Zhong RF, Liu CJ, Hao KX, Fan XD, Jiang JG. Polysaccharides from Flos Sophorae Immaturus ameliorates insulin resistance in IR-HepG2 cells by co-regulating signaling pathways of AMPK and IRS-1/PI3K/AKT. Int J Biol Macromol 2024; 280:136088. [PMID: 39366625 DOI: 10.1016/j.ijbiomac.2024.136088] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 09/18/2024] [Accepted: 09/25/2024] [Indexed: 10/06/2024]
Abstract
Four polysaccharides, named FSIP, FSIP-I, FSIP-II and FSIP-III, were isolated from Flos Sophorae Immaturus. Structure characterization revealed that FSIP-I and FSIP-II were types of AG-II-like polysaccharides while FSIP-III featured a RG-II-like structure with high content of GalpA. In vitro experiments showed that FSIPs upregulated HK and PK activities in glycolysis while downregulated G-6-Pase activities in gluconeogenesis. This increased glucose utilization while decreased the glucose synthesis in IR-HepG2 cells, potentially reducing elevated blood sugar levels induced by excess insulin. In terms of antioxidant system, FSIPs decreased the levels of ROS and MDA, and increased the activities of SOD and CAT, enhancing antioxidant capacity to counteract damage caused by insulin resistance in IR-HepG2 cells. To further explore the mechanism, related genes expressions were analyzed. The results found that FSIPs ameliorated insulin resistance via regulating AMPK and IRS-1/PI3K/AKT signal pathways. In the case of AMPK, glucose can be channeled into oxidative (catabolic) pathway, whereas, in the case of IRS-1/PI3K/AKT, glucose can be stored as glycogen (anabolic). This co-modulation could ameliorate insulin resistance by upregulating the glycolysis and repressing the gluconeogenesis in catabolism, and upregulating the glycogen synthesis in anabolism. Additionally, FSIP-III exhibited better anti-insulin resistance activity, attributed to its high content of GalpA.
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Affiliation(s)
- Rui-Fang Zhong
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China
| | - Chang-Jun Liu
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China
| | - Ke-Xin Hao
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China
| | - Xiao-Dan Fan
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China.
| | - Jian-Guo Jiang
- College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China.
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Wang T, Zhou D, Hong Z. Adipose tissue in older individuals: a contributing factor to sarcopenia. Metabolism 2024; 160:155998. [PMID: 39128607 DOI: 10.1016/j.metabol.2024.155998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 08/13/2024]
Abstract
Sarcopenia is a geriatric syndrome characterized by a functional decline in muscle. The prevalence of sarcopenia increases with natural aging, becoming a serious health problem among elderly individuals. Therefore, understanding the pathology of sarcopenia is critical for inhibiting age-related alterations and promoting health and longevity in elderly individuals. The development of sarcopenia may be influenced by interactions between visceral and subcutaneous adipose tissue and skeletal muscle, particularly under conditions of chronic low-grade inflammation and metabolic dysfunction. This hypothesis is supported by the following observations: (i) accumulation of senescent cells in both adipose tissue and skeletal muscle with age; (ii) gut dysbiosis, characterized by an imbalance in gut microbial communities as the main trigger for inflammation, sarcopenia, and aged adipose tissue; and (iii) microbial dysbiosis, which could impact the onset or progression of a senescent state. Moreover, adipose tissue acts as an endocrine organ, releasing molecules that participate in intricate communication networks between organs. Our discussion focuses on novel adipokines and their role in regulating adipose tissue and muscle, particularly those influenced by aging and obesity, emphasizing their contributions to disease development. On the basis of these findings, we propose that age-related adipose tissue and sarcopenia are disorders characterized by chronic inflammation and metabolic dysregulation. Finally, we explore new potential therapeutic strategies involving specialized proresolving mediator (SPM) G protein-coupled receptor (GPCR) agonists, non-SPM GPCR agonists, transient receptor potential (TRP) channels, antidiabetic drugs in conjunction with probiotics and prebiotics, and compounds designed to target senescent cells and mitigate their pro-inflammatory activity.
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Affiliation(s)
- Tiantian Wang
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
| | - Dong Zhou
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China
| | - Zhen Hong
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
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Wang F, Huynh PM, An YA. Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications. Compr Physiol 2024; 14:5581-5640. [PMID: 39382163 DOI: 10.1002/cphy.c230009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.
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Affiliation(s)
- Fenfen Wang
- Department of Anesthesiology, Critical Care, and Pain Medicine, Center for Perioperative Medicine, McGovern Medical School, UT Health Science Center at Houston, Houston, Texas, USA
| | - Phu M Huynh
- Department of Anesthesiology, Critical Care, and Pain Medicine, Center for Perioperative Medicine, McGovern Medical School, UT Health Science Center at Houston, Houston, Texas, USA
| | - Yu A An
- Department of Anesthesiology, Critical Care, and Pain Medicine, Center for Perioperative Medicine, McGovern Medical School, UT Health Science Center at Houston, Houston, Texas, USA
- Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, UT Health Science Center at Houston, Houston, Texas, USA
- Department of Biochemistry and Molecular Biology, McGovern Medical School, UT Health Science Center at Houston, Houston, Texas, USA
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Li J, Wei H, Wang N, Chen J, Zhang Y, An Z, Song J, Niu T, Wu W. Ozone-Induced Lung Injury are Mediated Via PPAR-Mediated Ferroptosis in Mice. Biol Trace Elem Res 2024:10.1007/s12011-024-04386-z. [PMID: 39370454 DOI: 10.1007/s12011-024-04386-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 09/17/2024] [Indexed: 10/08/2024]
Abstract
In recent years, the concentration of PM2.5 in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1 ppm, with 4 h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.
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Affiliation(s)
- Juan Li
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Huai Wei
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Ning Wang
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Jing Chen
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Ying Zhang
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Zhen An
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Jie Song
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Tianqi Niu
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China
| | - Weidong Wu
- International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China.
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Moon S, Park Y, Jang S, Kim S, Song DG, Shin DC, Lee CH. Interleukin-2 improves insulin sensitivity through hypothalamic sympathetic activation in obese mice. J Neuroinflammation 2024; 21:250. [PMID: 39367382 PMCID: PMC11453069 DOI: 10.1186/s12974-024-03244-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/24/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUND IL-2 regulates T cell differentiation: low-dose IL-2 induces immunoregulatory Treg differentiation, while high-dose IL-2 acts as a potent activator of cytotoxic T cells and NK cells. Therefore, high-dose IL-2 has been studied for use in cancer immunotherapy. We aimed to utilize low-dose IL-2 to treat inflammatory diseases such as obesity and insulin resistance, which involve low-grade chronic inflammation. MAIN BODY Systemic administration of low-dose IL-2 increased Treg cells and decreased inflammation in gonadal white adipose tissue (gWAT), leading to improved insulin sensitivity in high-fat diet-fed obese mice. Additionally, central administration of IL-2 significantly enhanced insulin sensitivity through the activation of the sympathetic nervous system. The sympathetic signaling induced by central IL-2 administration not only decreased interferon γ (IFNγ) + Th1 cells and the expression of pro-inflammatory cytokines, including Il-1β, Il-6, and Il-8, but also increased CD4 + CD25 + FoxP3 + Treg cells and Tgfβ expression in the gWAT of obese mice. These phenomena were accompanied by hypothalamic microgliosis and activation of pro-opiomelanocortin neurons. Furthermore, sympathetic denervation in gWAT reversed the enhanced insulin sensitivity and immune cell polarization induced by central IL-2 administration. CONCLUSION Overall, we demonstrated that IL-2 improves insulin sensitivity through two mechanisms: direct action on CD4 + T cells and via the neuro-immune axis triggered by hypothalamic microgliosis.
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Affiliation(s)
- Subin Moon
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Yejin Park
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Sooyeon Jang
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Saeha Kim
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Dan-Gyeong Song
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Dae-Chul Shin
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea
| | - Chan Hee Lee
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Republic of Korea.
- Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon, 24252, Republic of Korea.
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46
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Daurai B, Baruah AJ, Gogoi M. Recent advances in point-of-care biosensors for pancreatic diseases. Trends Analyt Chem 2024; 179:117867. [DOI: 10.1016/j.trac.2024.117867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Respekta-Długosz N, Mlyczyńska E, Pich K, Greggio A, Ramé C, Dupont J, Rak A. The adipokine profile in the plasma and anterior pituitary of pigs during the estrous cycle. Gen Comp Endocrinol 2024; 357:114588. [PMID: 39013539 DOI: 10.1016/j.ygcen.2024.114588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/03/2024] [Accepted: 07/13/2024] [Indexed: 07/18/2024]
Abstract
Adipokines play crucial roles in both reproductive and energy metabolic processes. This study aimed to compare the hormonal plasma profile of adiponectin, apelin, vaspin, chemerin, resistin, visfatin, and adipolin, and the expression of their receptors in the anterior pituitary (AP) between normal-weight Large White (LW) and fat Meishan (MS) pigs during different phases of the estrous cycle. We measured adipokine levels in the plasma and assessed their gene expression in the AP. We used Pearson's correlation analysis to examine potential links between adipokines levels, their receptors, and metabolic parameters (body weight; backfat thickness) and reproductive parameters (pituitary weight; age at puberty; levels of gonadotropins, steroid hormones; and gene expression of gonadotropin-releasing hormone receptor and gonadotropins in AP). The plasma levels of the evaluated adipokines fluctuated with phase and breed, except for visfatin and adipolin. Moreover, adipokine expression in AP varied significantly between breeds and estrous cycle phases, except for resistin receptor CAP1. Notably, we observed a positive correlation between plasma levels of adiponectin and its transcript in the AP only in MS pigs. Apelin gene expression correlated negatively with its receptor in MS, while we observed a breed-dependent correlation between chemerin gene expression and its receptor CMKLR1. We identified significant positive or negative correlations between adipokines or their receptor levels in plasma and AP as well as metabolic or reproductive parameters, depending on the breed. In conclusion, we have demonstrated breed-specific and estrous cycle-dependent regulation of adipokines in AP, underscoring their potential impact on metabolic and reproductive processes in swine.
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Affiliation(s)
- Natalia Respekta-Długosz
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow, Poland
| | - Ewa Mlyczyńska
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow, Poland
| | - Karolina Pich
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow, Poland
| | - Aleksandra Greggio
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland
| | - Christelle Ramé
- INRAE, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
| | - Joëlle Dupont
- INRAE, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
| | - Agnieszka Rak
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland.
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Huang P, Zhu Y, Qin J. Research advances in understanding crosstalk between organs and pancreatic β-cell dysfunction. Diabetes Obes Metab 2024; 26:4147-4164. [PMID: 39044309 DOI: 10.1111/dom.15787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 06/25/2024] [Accepted: 06/26/2024] [Indexed: 07/25/2024]
Abstract
Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between β-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β-cell dysfunction.
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Affiliation(s)
- Peng Huang
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yunling Zhu
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jian Qin
- Department of Traditional Chinese Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Quispe R, Sweeney T, Martin SS, Jones SR, Allison MA, Budoff MJ, Ndumele CE, Elshazly MB, Michos ED. Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2024; 13:e030548. [PMID: 39248264 PMCID: PMC11935629 DOI: 10.1161/jaha.123.030548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 03/06/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. METHODS AND RESULTS We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. CONCLUSIONS Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.
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Affiliation(s)
- Renato Quispe
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Seth S. Martin
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Steven R. Jones
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Matthew A. Allison
- Department of Family MedicineUniversity of California San DiegoSan DiegoCA
| | | | - Chiadi E. Ndumele
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Mohamed B. Elshazly
- Department of Cardiovascular MedicineHeart and Vascular Institute, Cleveland ClinicClevelandOH
| | - Erin D. Michos
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
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50
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Tumurbaatar B, Ogawa S, Nakamura N, Yamada T, Minato T, Mori Y, Saiki T, Matsubara T, Naruse K, Suda H. The effect of hydrogen gas on the oxidative stress response in adipose tissue. Sci Rep 2024; 14:21425. [PMID: 39271809 PMCID: PMC11399153 DOI: 10.1038/s41598-024-72626-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024] Open
Abstract
Oxidative stress in adipose tissue may alter the secretion pattern of adipocytokines and potentially promote atherosclerosis. However, the therapeutic role of hydrogen in adipose tissue under oxidative stress remains unclear. In this study, subcutaneous adipose tissue (SCAT) was collected from the mid-thoracic wounds of 12 patients who underwent open-heart surgery with a mid-thoracic incision. The adipose tissue was then immersed in a culture medium dissolved with hydrogen, which was generated using a hydrogen-generating device. The weight of the adipose tissue was measured before and after hydrogenation, and the tissue was immunostained for nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD), which are markers of oxidative stress. The immunostaining results showed that HO-1 and Nrf2 expression levels were significantly decreased in the hydrogenated group, whereas SOD expression levels increased, but did not attain statistical significance. Image analysis of adipose tissue revealed that a reduction in adipocyte size. Furthermore, hydrogenated adipose tissue showed a trend toward increased gene expression levels of adiponectin and decreased gene expression levels of chemerin, an adipocytokine involved in adipogenesis. These results demonstrated the therapeutic potential of hydrogen gas for oxidative stress in adipose tissue and for reducing adipocyte size.
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Affiliation(s)
- Batkhishig Tumurbaatar
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan
| | - Shinji Ogawa
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan
- Department of Cardiovascular Surgery, Toyokawa City Hospital, Toyokawa, 442-8561, Japan
| | - Nobuhisa Nakamura
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan.
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651, Japan.
| | - Toshiyuki Yamada
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan
- Department of Cardiovascular Surgery, Nagoya City University Midori Municipal Hospital, Nagoya, 458-0037, Japan
| | - Tomomi Minato
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651, Japan
- Department of Clinical Laboratory, Aichi Gakuin University Dental Hospital, Nagoya, 464-8651, Japan
| | - Yoshiharu Mori
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan
- Department of Cardiovascular Surgery, Toyokawa City Hospital, Toyokawa, 442-8561, Japan
| | - Tomokazu Saiki
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651, Japan
- Department of Pharmacy, Aichi Gakuin University Dental Hospital, Nagoya, 464-8651, Japan
| | - Tatsuaki Matsubara
- Faculty of Human Sciences, Aichi Mizuho College, Nagoya, 467-0867, Japan
| | - Keiko Naruse
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, 464-8651, Japan
| | - Hisao Suda
- Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467- 8601, Japan
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