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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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Zhong Y, Yan J, Lei Y, Zhang R, Abudurexiti A, Qi S, Hou W, Ma X. Lactucin and lactucopicrin ameliorate obesity in high-fat diet fed mice by promoting white adipose tissue browning through the activation of the AMPK/SIRT1/PGC-1α pathway. J Nutr Biochem 2025; 139:109851. [PMID: 39909319 DOI: 10.1016/j.jnutbio.2025.109851] [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: 06/20/2024] [Revised: 01/21/2025] [Accepted: 01/29/2025] [Indexed: 02/07/2025]
Abstract
Lactucin and lactucopicrin are the characteristic lipid-lowering active components found in Cichorium glandulosum. However, their effects and underlying mechanisms in obesity remain unclear. In the present study, C57BL/6J mice were simultaneously subjected to a high-fat diet (HFD) and treated with drugs to investigate the impacts of lactucin and lactucopicrin on HFD-induced obese mice. The results demonstrated that in HFD obese mice, lactucin and lactucopicrin significantly decreased body weight and the weights of adipose tissues, improved serum metabolic parameters, and increased the content of irisin. Regarding the intermediate metabolites of intestinal flora, which are closely associated with white adipose tissue (WAT) browning, lactucin and lactucopicrin treatment led to a reduction in the levels of 12-α-OH/non-12-α-OH bile acids (BAs) and also tended to enhance the levels of short-chain fatty acids (SCFAs). qRT-PCR results indicated that lactucin and lactucopicrin treatment elevated the expression levels of genes related to beige fat markers, thermogenesis, mitochondrial biogenesis, and lipolysis in WAT, as well as those of thermogenesis and lipolysis genes in brown adipose tissue (BAT). Western blot analysis revealed that lactucin and lactucopicrin up-regulated the expression of uncoupling protein 1 (UCP1), the core protein in thermogenesis, in both WAT and BAT. Moreover, they also up-regulated the expression levels of AMP-activated kinase (AMPK), sirtuin 1 (SIRT1), and PPARγ coactivator 1-alpha (PGC-1α), which are key pathway proteins involved in WAT browning. Furthermore, 16S rRNA sequencing results showed that in HFD obese mice, lactucin and lactucopicrin improved the composition and function of the intestinal microbiota. In conclusion, lactucin and lactucopicrin may promote WAT browning by activating the AMPK/SIRT1/PGC-1α pathway, thereby ameliorating obesity in HFD mice.
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Affiliation(s)
- Yewei Zhong
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Junlin Yan
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Yi Lei
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Rui Zhang
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | | | - Shuwen Qi
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Wenhui Hou
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Xiaoli Ma
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
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Zhao J, Yang Z, Liu H, Yang C, Chen Y, Cao Q, Jiang J. Dietary Methionine Hydroxy Analog Regulates Hepatic Lipid Metabolism via SIRT1/AMPK Signaling Pathways in Largemouth Bass Micropterus salmodies. BIOLOGY 2025; 14:227. [PMID: 40136484 PMCID: PMC11939594 DOI: 10.3390/biology14030227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/14/2025] [Accepted: 02/20/2025] [Indexed: 03/27/2025]
Abstract
This experiment was arranged to explore the impacts of dietary MHA on liver lipid metabolism in largemouth bass. A total of 480 fish (14.49 ± 0.13 g) were randomly allocated into four groups, each with three replicates. They were then given four different diets containing graded levels of MHA (0.0, 3.0, 6.0, and 9.0 g/kg) for 84 days. The results showed that dietary MHA increased hepatic lipid vacuoles and lipid content (p < 0.05). Dietary supplementation with MHA 9.0 g/kg diets increased the activities of acetyl-coA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-coA desaturase 1 (SCD-1). Dietary MHA up-regulated the mRNA expressions of liver lipid synthesis (ACC, FAS, SCD-1 and SREBP-1c) (p < 0.05). Furthermore, compared with the 0.0 g/kg diet group, the group supplemented with 9.0 g/kg MHA in the diet exhibited a significant decrease in the activities of liver lipid-oxidation-related enzymes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1), as well as HSL and CPT1) and the gene expressions of ATGL, HSLa, HSLb, CPT1a, and PPARα (p < 0.05). Additionally, the mRNA expressions and protein levels of SIRT1 and AMPK in the 9.0 g/kg MHA-supplemented group were significantly lower than those in the 0.0 g/kg diet group (p < 0.05). Overall, the present results suggested that dietary MHA could increase lipid accumulation through regulating SIRT1/AMPK signaling pathways in the livers of largemouth bass.
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Affiliation(s)
- Ju Zhao
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Zhongjie Yang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Haifeng Liu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Chao Yang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Yujun Chen
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Quanquan Cao
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
| | - Jun Jiang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (J.Z.); (Z.Y.); (H.L.); (C.Y.); (Y.C.)
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya’an 625014, China
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Liu Y, Wang Z, Xi W, Yuan J, Zhang K, Liu H, Zhao J, Wang Y. Lactiplantibacillus plantarum improves the growth performance and meat quality of broilers by regulating the cecal microbiota and metabolites. Front Microbiol 2025; 16:1519552. [PMID: 39935642 PMCID: PMC11811115 DOI: 10.3389/fmicb.2025.1519552] [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: 10/30/2024] [Accepted: 01/14/2025] [Indexed: 02/13/2025] Open
Abstract
Gut microbiota can digest and ferment feed into metabolites to influence the meat quality. Probiotics are used to regulate the gut microbiota. In this study, a total of 360 broilers were assigned to 4 treatments (10 broilers per cage): control (Con), low dose of Lactiplantibacillus plantarum HW1 (Lp_L), medium dose of Lp (Lp_M) and high dose of Lp (Lp_H) for a 42-day experimental period. Results showed that the Lp treatments improved the growth performance, carcass traits, breast meat quality, and also influenced the fatty acids composition, including the decrease of n-6PUFA/n-3PUFA, and the increase of C18:3n3, ∑n-3PUFA and PUFA/SFA. The lipid metabolism-related gene expressions in the liver showed that Lp treatments increased the expression of AMPK, CPT-1α, PPARα, ATGL and also decreased the expression of PPARγ, SREBP-1c, ACC, FAS, LPL, and SCD. Moreover, the abundances of gut microbiota, such as Synergistaceae and Synergistes were influenced by the Lp treatments. Functional prediction of the gut microbiota indicated that pathways, including pancreatic secretion and spliceosome were enriched by the Lp treatments. Untargeted metabolomics revealed that the Lp treatments altered the content of metabolites, such as 6-ketomyristic acid and indole-3-acetamide. These metabolites were enriched in pathways including fatty acid metabolism. Correlation analyses revealed potential interactions between growth performance and meat quality, as well as gut microbiota (Synergistes, etc.) and metabolites (6-ketomyristic acid, etc.). Overall, our data show that the Lp treatments significantly improved the growth performance, carcass traits and meat quality of broilers by regulating fatty acids, gut microbiota and metabolites.
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Affiliation(s)
| | | | | | | | | | | | | | - Yang Wang
- College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China
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Rehman IU, Park JS, Choe K, Park HY, Park TJ, Kim MO. Overview of a novel osmotin abolishes abnormal metabolic-associated adiponectin mechanism in Alzheimer's disease: Peripheral and CNS insights. Ageing Res Rev 2024; 100:102447. [PMID: 39111409 DOI: 10.1016/j.arr.2024.102447] [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: 06/11/2024] [Revised: 07/19/2024] [Accepted: 08/03/2024] [Indexed: 08/16/2024]
Abstract
Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD.
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Affiliation(s)
- Inayat Ur Rehman
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.
| | - Jun Sung Park
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.
| | - Kyonghwan Choe
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht 6229 ER, the Netherlands.
| | - Hyun Young Park
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht 6229 ER, the Netherlands; Department of Pediatrics, Maastricht University Medical Center (MUMC+), Maastricht 6202 AZ, the Netherlands.
| | - Tae Ju Park
- Haemato-oncology/Systems Medicine Group, Paul O'Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences (MVLS), University of Glasgow, Glasgow G12 0ZD, United Kingdom.
| | - Myeong Ok Kim
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea; Alz-Dementia Korea Co., Jinju 52828, Republic of Korea.
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Salminen A. AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration. Biogerontology 2024; 25:83-106. [PMID: 37917219 PMCID: PMC10794430 DOI: 10.1007/s10522-023-10072-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 09/26/2023] [Indexed: 11/04/2023]
Abstract
Disruption of the extracellular matrix (ECM) and an accumulation of fibrotic lesions within tissues are two of the distinctive hallmarks of the aging process. Tissue fibroblasts are mesenchymal cells which display an impressive plasticity in the regulation of ECM integrity and thus on tissue homeostasis. Single-cell transcriptome studies have revealed that tissue fibroblasts exhibit a remarkable heterogeneity with aging and in age-related diseases. Excessive stress and inflammatory insults induce the differentiation of fibroblasts into myofibroblasts which are fusiform contractile cells and abundantly secrete the components of the ECM and proteolytic enzymes as well as many inflammatory mediators. Detrimental stresses can also induce the transdifferentiation of certain mesenchymal and myeloid cells into myofibroblasts. Interestingly, many age-related stresses, such as oxidative and endoplasmic reticulum stresses, ECM stiffness, inflammatory mediators, telomere shortening, and several alarmins from damaged cells are potent inducers of myofibroblast differentiation. Intriguingly, there is convincing evidence that the signaling pathways stimulated by the AMP-activated protein kinase (AMPK) are potent inhibitors of myofibroblast differentiation and accordingly AMPK signaling reduces fibrotic lesions within tissues, e.g., in age-related cardiac and pulmonary fibrosis. AMPK signaling is not only an important regulator of energy metabolism but it is also able to control cell fate determination and many functions of the immune system. It is known that AMPK signaling can delay the aging process via an integrated signaling network. AMPK signaling inhibits myofibroblast differentiation, e.g., by suppressing signaling through the TGF-β, NF-κB, STAT3, and YAP/TAZ pathways. It seems that AMPK signaling can alleviate age-related tissue fibrosis and degeneration by inhibiting the differentiation of myofibroblasts.
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Affiliation(s)
- Antero Salminen
- Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
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Yu H, Gao X, Ge Q, Tai W, Hao X, Shao Q, Fang Z, Chen M, Song Y, Gao W, Liu G, Du X, Li X. Tumor necrosis factor-α reduces adiponectin production by decreasing transcriptional activity of peroxisome proliferator-activated receptor-γ in calf adipocytes. J Dairy Sci 2023; 106:5182-5195. [PMID: 37268580 DOI: 10.3168/jds.2022-22919] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/24/2023] [Indexed: 06/04/2023]
Abstract
Adiponectin (encoded by ADIPOQ) is an adipokine that orchestrates energy homeostasis by modulating glucose and fatty acid metabolism in peripheral tissues. During the periparturient period, dairy cows often develop adipose tissue inflammation and decreased plasma adiponectin levels. Proinflammatory cytokine tumor necrosis factor-α (TNF-α) plays a pivotal role in regulating the endocrine functions of adipocytes, but whether it affects adiponectin production in calf adipocytes remains obscure. Thus, the present study aimed to determine whether TNF-α could affect adiponectin production in calf adipocytes and to identify the underlying mechanism. Adipocytes isolated from Holstein calves were differentiated and used for (1) BODIPY493/503 staining; (2) treatment with 0.1 ng/mL TNF-α for different times (0, 8, 16, 24, or 48 h); (3) transfection with peroxisome proliferator-activated receptor-γ (PPARG) small interfering RNA for 48 h followed by treatment with or without 0.1 ng/mL TNF-α for 24 h; and (4) overexpression of PPARG for 48 h followed by treatment with or without 0.1 ng/mL TNF-α for 24 h. After differentiation, obvious lipid droplets and secretion of adiponectin were observed in adipocytes. Treatment with TNF-α did not alter mRNA abundance of ADIPOQ but reduced the total and high molecular weight (HMW) adiponectin content in the supernatant of adipocytes. Quantification of mRNA abundance of endoplasmic reticulum (ER)/Golgi resident chaperones involved in adiponectin assembly revealed that ER protein 44 (ERP44), ER oxidoreductase 1α (ERO1A), and disulfide bond-forming oxidoreductase A-like protein (GSTK1) were downregulated in TNF-α-treated adipocytes, while 78-kDa glucose-regulated protein and Golgi-localizing γ-adaptin ear homology domain ARF binding protein-1 were unaltered. Moreover, TNF-α diminished nuclear translocation of PPARγ and downregulated mRNA abundance of PPARG and its downstream target gene fatty acid synthase, suggesting that TNF-α suppressed the transcriptional activity of PPARγ. In the absence of TNF-α, overexpression of PPARG enhanced the total and HMW adiponectin content in supernatant and upregulated the mRNA abundance of ADIPOQ, ERP44, ERO1A, and GSTK1 in adipocytes. However, knockdown of PPARG reduced the total and HMW adiponectin content in supernatant and downregulated the mRNA abundance of ADIPOQ, ERP44, ERO1A, and GSTK1 in adipocytes. In the presence of TNF-α, overexpression of PPARG decreased, while knockdown of PPARG further exacerbated TNF-α-induced reductions in total and HMW adiponectin secretion and gene expression of ERP44, ERO1A, and GSTK1. Overall, TNF-α reduces adiponectin assembly in the calf adipocyte, which may be partly mediated by attenuation of PPARγ transcriptional activity. Thus, locally elevated levels of TNF-α in adipose tissue may be one reason for the decrease in circulating adiponectin in periparturient dairy cows.
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Affiliation(s)
- Hao Yu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Xinxing Gao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Qilai Ge
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Wenjun Tai
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Xue Hao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Qi Shao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Zhiyuan Fang
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Meng Chen
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Yuxiang Song
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Wenwen Gao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Guowen Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China
| | - Xiliang Du
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China.
| | - Xinwei Li
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China.
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Atashi H, Bastin C, Wilmot H, Vanderick S, Hubin X, Gengler N. Genome-wide association study for selected cheese-making properties in Dual-Purpose Belgian Blue cows. J Dairy Sci 2022; 105:8972-8988. [PMID: 36175238 DOI: 10.3168/jds.2022-21780] [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: 01/04/2022] [Accepted: 06/21/2022] [Indexed: 01/05/2023]
Abstract
This study aimed to estimate genetic parameters and identify genomic region(s) associated with selected cheese-making properties (CMP) in Dual-Purpose Belgian Blue (DPBB) cows. Edited data were 46,301 test-day records of milk yield, fat percentage, protein percentage, casein percentage, milk calcium content (CC), coagulation time (CT), curd firmness after 30 min from rennet addition (a30), and milk titratable acidity (MTA) collected from 2014 to 2020 on 4,077 first-parity (26,027 test-day records), and 3,258 second-parity DPBB cows (20,274 test-day records) distributed in 124 herds in the Walloon Region of Belgium. Data of 28,266 SNP, located on 29 Bos taurus autosomes (BTA) of 1,699 animals were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method. The SNP solutions were estimated using a single-step genomic BLUP approach. The proportion of the total additive genetic variance explained by windows of 25 consecutive SNPs (with an average size of ∼2 Mb) was calculated, and regions accounting for at least 1.0% of the total additive genetic variance were used to search for candidate genes. Heritability estimates for the included CMP ranged from 0.19 (CC) to 0.50 (MTA), and 0.24 (CC) to 0.41 (MTA) in the first and second parity, respectively. The genetic correlation estimated between CT and a30 varied from -0.61 to -0.41 and from -0.55 to -0.38 in the first and second lactations, respectively. Negative genetic correlations were found between CT and milk yield and composition, while those estimated between curd firmness and milk composition were positive. Genome-wide association analyses results identified 4 genomic regions (BTA1, BTA3, BTA7, and BTA11) associated with the considered CMP. The identified genomic regions showed contrasting results between parities and among the different stages of each parity. It suggests that different sets of candidate genes underlie the phenotypic expression of the considered CMP between parities and lactation stages of each parity. The findings of this study can be used for future implementation and use of genomic evaluation to improve the cheese-making traits in DPBB cows.
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Affiliation(s)
- H Atashi
- TERRA Teaching and Research Center, Gembloux Agro-Bio Tech, University of Liège, 5030 Gembloux, Belgium; Department of Animal Science, Shiraz University, 71441-65186 Shiraz, Iran.
| | - C Bastin
- Walloon Breeders Association, 5590 Ciney, Belgium
| | - H Wilmot
- TERRA Teaching and Research Center, Gembloux Agro-Bio Tech, University of Liège, 5030 Gembloux, Belgium; National Fund for Scientific Research (FRS-FNRS), Rue d'Egmont 5, B-1000 Brussels, Belgium
| | - S Vanderick
- TERRA Teaching and Research Center, Gembloux Agro-Bio Tech, University of Liège, 5030 Gembloux, Belgium
| | - X Hubin
- Walloon Breeders Association, 5590 Ciney, Belgium
| | - N Gengler
- TERRA Teaching and Research Center, Gembloux Agro-Bio Tech, University of Liège, 5030 Gembloux, Belgium
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Kra G, Daddam JR, Moallem U, Kamer H, Kočvarová R, Nemirovski A, Contreras GA, Tam J, Zachut M. Effects of omega-3 supplementation on components of the endocannabinoid system and metabolic and inflammatory responses in adipose and liver of peripartum dairy cows. J Anim Sci Biotechnol 2022; 13:114. [PMID: 36183098 PMCID: PMC9526899 DOI: 10.1186/s40104-022-00761-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 07/31/2022] [Indexed: 12/18/2022] Open
Abstract
Background Dietary supplementation of omega-3 fatty acids can reduce the activation of the endocannabinoid system (ECS) by decreasing the availability of arachidonic acid, thus lowering endocannabinoids (eCBs) levels. The ECS is a modulator of energy metabolism, stress response and inflammation in mammals, yet there is little information on the roles of the ECS in transition dairy cows. During the periparturient period, the adipose tissue and liver are the main metabolic organs that participate in the adaptations of dairy cows to onset of lactation; however, exceeded adipose tissue lipolysis and accumulation of lipids in the liver have adverse effects on cows’ physiology. Here we aimed to examine whether omega-3 supplementation during the transition period will modulate ECS activation and affect metabolic and inflammatory indices in postpartum dairy cows, by supplementing twenty-eight transition Holstein dairy cows with either saturated fat (CTL) or encapsulated flaxseed oil (FLX). Components of the ECS, metabolic and inflammatory markers were measured in blood, liver, and subcutaneous adipose tissue. Results FLX supplementation reduced feed intake by 8.1% (P < 0.01) and reduced plasma levels of arachidonic acid (by 44.2%; P = 0.02) and anandamide (by 49.7%; P = 0.03) postpartum compared to CTL. The mRNA transcription levels of the cannabinoid receptor 1 (CNR1/CB1) tended to be lower (2.5 folds) in white blood cells of FLX than in CTL (P = 0.10), and protein abundance of ECS enzyme monoacylglycerol lipase was higher in peripheral blood mononuclear cells of FLX than in CTL (P = 0.04). In adipose tissue, palmitoylethanolamide levels were lower in FLX than in CTL (by 61.5%; P = 0.02), relative mRNA transcription of lipogenic genes were higher, and the protein abundance of cannabinoid receptor 2 (P = 0.08) and monoacylglycerol lipase (P = 0.10) tended to be higher in FLX compared to CTL. Hepatic 2-arachidonoylglycerol tended to be higher (by 73.1%; P = 0.07), and interlukin-6 mRNA transcription level was 1.5 folds lower in liver of FLX than in CTL (P = 0.03). Conclusions Nutritional supplementation of omega-3 fatty acids seems to partly modulate ECS activation, which could be related to lower feed intake. The altered ECS components in blood, adipose tissue and liver are associated with moderate modulations in lipid metabolism in the adipose and inflammation in liver of peripartum dairy cows. Supplementary Information The online version contains supplementary material available at 10.1186/s40104-022-00761-9.
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Affiliation(s)
- Gitit Kra
- Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Rishon LeZion, Israel.,Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Jayasimha Rayalu Daddam
- Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Rishon LeZion, Israel
| | - Uzi Moallem
- Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Rishon LeZion, Israel
| | - Hadar Kamer
- Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Rishon LeZion, Israel
| | - Radka Kočvarová
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Alina Nemirovski
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - G Andres Contreras
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Joseph Tam
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Maya Zachut
- Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Rishon LeZion, Israel.
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10
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Wu KJ, Liu PP, Chen MY, Zhou MX, Liu X, Yang Q, Xu L, Gong Z. The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis. Front Nutr 2022; 9:904557. [PMID: 35873419 PMCID: PMC9301321 DOI: 10.3389/fnut.2022.904557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 06/06/2022] [Indexed: 11/13/2022] Open
Abstract
Excessive alcohol consumption can eventually progress to alcoholic liver disease (ALD). The underlying mechanism of ALD toxicity is primarily associated with oxidative damage. Many alkaloids have been reported to possess potential antioxidative efficacy, while the mechanism of their hepatoprotective activity against ALD is still not clear. In this study, eight alkaloids were selected from a monomer library of Traditional Chinese Medicine and evaluated for their antioxidant activity against ALD by the evaluation of Glutathione (GSH) and Malondialdehyde (MDA). The result suggested that Leonurine hydrochloride (LH) was a potent antioxidant that could reduce alcoholic liver damage. To further investigate the underlying mechanism of LH against ALD, the molecular pathway induced by LH was identified by RNA-seq analyses. Transcriptome data revealed the principal mechanism for the protective effect of LH against ALD might be attributed to the differentially expressed genes (DEGs) of PI3K-AKT, AMPK, and HIF-1 signaling pathways involved in the lipid metabolism. Given the hepatoprotective mechanism of LH is involved in lipid metabolism, the lipid metabolism induced by LH was further analyzed by UHPLC-MS/MS. Metabolome analysis indicated that LH significantly regulated glycerophospholipid metabolism including phosphatidylcholine, 1-acyl-sn-glycero-3-phosphocholine, phosphatidylethanolamine and 1-acyl-sn-glycero-3-phosphoethanolamine in the liver. Overall, this study revealed that the hepatoprotective mechanism of LH against alcoholic liver damage might be associated with the genes involved in glycerophospholipid metabolism.
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11
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Zare M, Atashi H, Hostens M. Genome-Wide Association Study for Lactation Performance in the Early and Peak Stages of Lactation in Holstein Dairy Cows. Animals (Basel) 2022; 12:ani12121541. [PMID: 35739877 PMCID: PMC9219502 DOI: 10.3390/ani12121541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/27/2022] [Accepted: 06/10/2022] [Indexed: 11/24/2022] Open
Abstract
Simple Summary Although genome-wide association studies (GWAS) have been carried out within a variety of cattle breeds, they are mainly based on the accumulated 305-day lactation yield traits estimated by summing the test-day recorded every day during the lactation period, or combining the weekly or monthly test-day records by linear interpolation. Since the additive genetic variance for milk yield and composition changes during lactation, the genetic effects of QTL related to these traits are not constant during the lactation period. Therefore, a better understanding of the genetic architecture of milk production traits in different lactation stages (e.g., beginning, peak, and end stages of lactation) is needed. The aim of this study was to detect genomic loci associated with lactation performance during 9 to 50 days in milk (DIM) in Holstein dairy cows. Candidate genes identified for milk production traits showed contrasting results between the EARLY and PEAK stages of lactation. Based on the results of this study, it can be concluded that in any genomic study it should be taken into account that the genetic effects of genes related to the lactation performance are not constant during the lactation period. Abstract This study aimed to detect genomic loci associated with the lactation performance during 9 to 50 days in milk (DIM) in Holstein dairy cows. Daily milk yield (MY), fat yield (FY), and protein yield (PY) during 9 to 50 DIM were recorded on 134 multiparous Holstein dairy cows distributed in four research herds. Fat- and protein-corrected milk (FPCM), fat-corrected milk (FCM), and energy-corrected milk (ECM) were predicted. The records collected during 9 to 25 DIM were put into the early stage of lactation (EARLY) and those collected during 26 to 50 DIM were put into the peak stage of lactation (PEAK). Then, the mean of traits in each cow included in each lactation stage (EARLY and PEAK) were estimated and used as phenotypic observations for the genome-wide association study. The included animals were genotyped with the Illumina BovineHD Genotyping BeadChip (Illumina Inc., San Diego, CA, USA) for a total of 777,962 single nucleotide polymorphisms (SNPs). After quality control, 585,109 variants were analyzed using GEMMA software in a mixed linear model. Although there was no SNP associated with traits included at the 5% genome-wide significance threshold, 18 SNPs were identified to be associated with milk yield and composition at the suggestive genome-wide significance threshold. Candidate genes identified for milk production traits showed contrasting results between the EARLY and PEAK stages of lactation. This suggests that differential sets of candidate genes underlie the phenotypic expression of the considered traits in the EARLY and PEAK stages of lactation. Although further functional studies are needed to validate our findings in independent populations, it can be concluded that in any genomic study it should be taken into account that the genetic effects of genes related to the lactation performance are not constant during the lactation period.
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Affiliation(s)
- Mahsa Zare
- Department of Animal Science, Shiraz University, Shiraz 7144113131, Iran; (M.Z.); (H.A.)
| | - Hadi Atashi
- Department of Animal Science, Shiraz University, Shiraz 7144113131, Iran; (M.Z.); (H.A.)
| | - Miel Hostens
- Department of Population Health Sciences, University of Utrecht, Yalelaan 7, 3584 CL Utrecht, The Netherlands
- Correspondence: ; Tel.: +31-30-253-1820
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12
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Chen S, Yang M, Wang R, Fan X, Tang T, Li P, Zhou X, Qi K. Suppression of high-fat-diet-induced obesity in mice by dietary folic acid supplementation is linked to changes in gut microbiota. Eur J Nutr 2022; 61:2015-2031. [PMID: 34993642 DOI: 10.1007/s00394-021-02769-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 12/03/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE To investigate whether the effects of dietary folic acid supplementation on body weight gain are mediated by gut microbiota in obesity. METHODS Male C57 BL/6J conventional (CV) and germ-free (GF) mice both aged three to four weeks were fed a high-fat diet (HD), folic acid-deficient HD (FD-HD), folic acid-supplement HD (FS-HD) and a normal-fat diet (ND) for 25 weeks. Faecal microbiota were analyzed by 16S rRNA high-throughput sequencing, and the mRNA expression of genes was determined by the real-time RT-PCR. Short-chain fatty acids (SCFAs) in faeces and plasma were measured using gas chromatography-mass spectrometry. RESULTS In CV mice, HD-induced body weight gain was inhibited by FS-HD, accompanied by declined energy intake, smaller white adipocyte size, and less whitening of brown adipose tissue. Meanwhile, the HD-induced disturbance in the expression of fat and energy metabolism-associated genes (Fas, Atgl, Hsl, Ppar-α, adiponectin, resistin, Ucp2, etc.) in epididymal fat was diminished, and the dysbiosis in faecal microbiota was lessened, by FS-HD. However, in GF mice with HD feeding, dietary folic acid supplementation had almost no effect on body weight gain and the expression of fat- and energy-associated genes. Faecal or plasma SCFA concentrations in CV and GF mice were not altered by either FD-HD or FS-HD feeding. CONCLUSION Dietary folic acid supplementation differently affected body weight gain and associated genes' expression under HD feeding between CV and GF mice, suggesting that gut bacteria might partially share the responsibility for beneficial effects of dietary folate on obesity.
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Affiliation(s)
- Si Chen
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Mengyi Yang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Rui Wang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Xiuqin Fan
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Tiantian Tang
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Ping Li
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Xinhui Zhou
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China
| | - Kemin Qi
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institutue, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-li-shi Road, Beijing, 100045, China.
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13
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Zheng YT, Xiao TM, Wu CX, Cheng JY, Li LY. Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2022; 13:798417. [PMID: 35399941 PMCID: PMC8983824 DOI: 10.3389/fendo.2022.798417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 02/22/2022] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two. METHODS The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01). CONCLUSION Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.
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14
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Bao T, Liu J, Leng J, Cai L. The cGAS-STING pathway: more than fighting against viruses and cancer. Cell Biosci 2021; 11:209. [PMID: 34906241 PMCID: PMC8670263 DOI: 10.1186/s13578-021-00724-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 12/02/2021] [Indexed: 01/07/2023] Open
Abstract
In the classic Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, downstream signals can control the production of type I interferon and nuclear factor kappa-light-chain-enhancer of activated B cells to promote the activation of pro-inflammatory molecules, which are mainly induced during antiviral responses. However, with progress in this area of research, studies focused on autoimmune diseases and chronic inflammatory conditions that may be relevant to cGAS-STING pathways have been conducted. This review mainly highlights the functions of the cGAS-STING pathway in chronic inflammatory diseases. Importantly, the cGAS-STING pathway has a major impact on lipid metabolism. Different research groups have confirmed that the cGAS-STING pathway plays an important role in the chronic inflammatory status in various organs. However, this pathway has not been studied in depth in diabetes and diabetes-related complications. Current research on the cGAS-STING pathway has shown that the targeted therapy of diseases that may be caused by inflammation via the cGAS-STING pathway has promising outcomes.
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Affiliation(s)
- Terigen Bao
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, 130021, China
- Department of Pediatrics, The Pediatric Research Institute, The University of Louisville School of Medicine, Louisville, KY, 40292, USA
| | - Jia Liu
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, 130021, China
| | - Jiyan Leng
- Department of Geriatrics, The First Hospital of Jilin University, Changchun, 130021, China.
| | - Lu Cai
- Department of Pediatrics, The Pediatric Research Institute, The University of Louisville School of Medicine, Louisville, KY, 40292, USA
- Departments of Pharmacology and Toxicology, The University of Louisville School of Medicine, Louisville, KY, USA
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15
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Ding H, Li Y, Liu L, Hao N, Zou S, Jiang Q, Liang Y, Ma N, Feng S, Wang X, Wu J, Loor JJ. Sirtuin 1 is involved in oleic acid-induced calf hepatocyte steatosis via alterations in lipid metabolism-related proteins. J Anim Sci 2021; 99:6358199. [PMID: 34436591 DOI: 10.1093/jas/skab250] [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: 06/11/2021] [Accepted: 08/24/2021] [Indexed: 11/14/2022] Open
Abstract
Sirtuin 1 (SIRT1), an NAD-dependent protein deacetylase, plays a central role in the control of lipid metabolism in nonruminants. However, the role of SIRT1 in hepatic lipid metabolism in dairy cows with fatty liver is not well known. Thus, we used isolated primary bovine hepatocytes to determine the role of SIRT1 in protecting cells against oleic acid (OA)-induced steatosis. Recombinant adenoviruses to overexpress (AD-GFP-SIRT1-E) or knockdown (AD-GFP-SIRT1-N) SIRT1 were used for transduction of hepatocytes. Calf hepatocytes isolated from five female calves (1 d old, 30 to 40 kg) were used to determine both time required and the lowest dose of OA that could induce triacylglycerol (TAG) accumulation. Analyses indicated that 0.25 mM OA for 24 h was suitable to induce TAG accumulation. In addition, OA not only led to an increase in TAG, but also upregulated mRNA and protein abundance of sterol regulatory element-binding transcription factor 1 (SREBF1) and downregulated SIRT1 and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PPARGC1A). Thus, these in vitro conditions were deemed optimal for subsequent experiments. Calf hepatocytes were cultured and incubated with OA (0.25 mM) for 24 h, followed by adenoviral AD-GFP-SIRT1-E or AD-GFP-SIRT1-N transduction for 48 h. Overexpression of SIRT1 led to greater protein and mRNA abundance of SIRT1 along with fatty acid oxidation-related genes including PPARGC1A, peroxisome proliferator-activated receptor alpha (PPARA), retinoid X receptor α (RXRA), and ratio of phospho-acetyl-CoA carboxylase alpha (p-ACACA)/total acetyl-CoA carboxylase alpha (ACACA). In contrast, it resulted in lower protein and mRNA abundance of genes related to lipid synthesis including SREBF1, fatty acid synthase (FASN), apolipoprotein E (APOE), and low-density lipoprotein receptor (LDLR). The concentration of TAG decreased due to SIRT1 overexpression. In contrast, silencing SIRT1 led to lower protein and mRNA abundance of SIRT1, PPARGC1A, PPARA, RXRA, and greater protein and mRNA abundance of SREBF1, FASN, APOE, and LDLR. Further, those responses were accompanied by greater content of cellular TAG and total cholesterol (TC). Overall, data from these in vitro studies indicated that SIRT1 is involved in the regulation of lipid metabolism in calf hepatocytes subjected to an increase in the supply of OA. Thus, it is possible that alterations in SIRT1 abundance and activity in vivo contribute to development of fatty liver in dairy cows.
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Affiliation(s)
- Hongyan Ding
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Yu Li
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China.,Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Hefei 230036, Anhui, China
| | - Leihong Liu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Ning Hao
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Suping Zou
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Qianming Jiang
- Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA
| | - Yusheng Liang
- Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA
| | - Nana Ma
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China
| | - Shibing Feng
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Xichun Wang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Jinjie Wu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Juan J Loor
- Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA
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16
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Jin M, Shen Y, Pan T, Zhu T, Li X, Xu F, Betancor MB, Jiao L, Tocher DR, Zhou Q. Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream ( Acanthopagrus schlegelii). Front Immunol 2021; 12:694720. [PMID: 34248992 PMCID: PMC8261298 DOI: 10.3389/fimmu.2021.694720] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/07/2021] [Indexed: 11/13/2022] Open
Abstract
The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.
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Affiliation(s)
- Min Jin
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Yuedong Shen
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Tingting Pan
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Tingting Zhu
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Xuejiao Li
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Fangmin Xu
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Mónica B Betancor
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, United Kingdom
| | - Lefei Jiao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
| | - Douglas R Tocher
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, United Kingdom.,Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University, Shantou, China
| | - Qicun Zhou
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo, China
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Zeb F, Wu X, Fatima S, Zaman MH, Khan SA, Safdar M, Alam I, Feng Q. Time-restricted feeding regulates molecular mechanisms with involvement of circadian rhythm to prevent metabolic diseases. Nutrition 2021; 89:111244. [PMID: 33930788 DOI: 10.1016/j.nut.2021.111244] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/03/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023]
Abstract
Lifestyle and genetic perturbation of circadian rhythm can trigger the incidence and severity of metabolic diseases. Time-restricted feeding (TRF) regulates the circadian rhythm of food intake that protects against metabolic disorders induced by adverse nutrient intake. TRF also executes host metabolism from nutrient availability to optimize nutrient utilization. Circadian clock and nutrient-sensing pathways coordinate to regulate metabolic health through the feeding/fasting cycle. Concurrently, TRF imposes diurnal rhythm in nutrient utilization, thereby preserving cellular homeostasis. However, modulation of daily feeding and fasting periods calibrates the circadian clock, which protects against the lethal effects of nutrient imbalance on metabolism. Therefore, TRF also improves and restores metabolic rhythms that ultimately lead to better fitness by reversing the alteration in genotype-specific gene expression. The aim of this review was to summarize that TRF is an emerging dietary approach that maintains robust circadian rhythms in support of a steady daily feeding and fasting cycle. TRF also encourages the coordination between circadian clock components and nutrient-sensing pathways via molecular effectors that exert a protective role in the prevention of metabolic diseases.
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Affiliation(s)
- Falak Zeb
- Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Human Nutrition and Dietetics, National University of Medical Sciences, Islamabad, Pakistan.
| | - Xiaoyue Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Sanyia Fatima
- Department of Psychology, Help and Hand Rehabilitation Institute, Ripah International University Islamabad, Pakistan
| | | | - Shahbaz Ali Khan
- Department of Neurosurgery, Ayub Medical College Abbottabad, Pakistan
| | - Mahpara Safdar
- Department of Environmental Design, Health & Nutritional Sciences, Faculty of Sciences, Allama Iqbal Open University, Islamabad, Pakistan
| | - Iftikhar Alam
- Department of Human Nutrition and Dietetics, Bacha Khan University Charsadda KP, Pakistan
| | - Qing Feng
- Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, China
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Zhang Z, Ni L, Zhang L, Zha D, Hu C, Zhang L, Feng H, Wei X, Wu X. Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy. Diabetes Metab Syndr Obes 2021; 14:227-240. [PMID: 33500643 PMCID: PMC7822229 DOI: 10.2147/dmso.s289712] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 12/24/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Abnormal lipid deposition in the progress of diabetic nephropathy (DN) plays an important role in a number of studies that have shown that SGLT2 inhibitor (SGLT2i) empagliflozin plays an important role in lipid metabolism, but its mechanism is still unclear. METHODS We aimed to explore the effect of empagliflozin on lipid levels in kidney cancer patients with DN and postoperative patients without DN kidney carcinoma; the patients with DN showed ectopic lipid deposition. In type 2 diabetes model mice induced by streptozotocin (STZ) and a high-fat diet, combined AMPK plus empagliflozin or empagliflozin inhibitor plus compound C was applied, followed by analyses of the blood, urine and kidney indexes to observe the correlation between SGLT2i and AMPK and lipid metabolism in diabetic kidney disease. We determined whether DN in patients with renal tubular atrophy involved lipid metabolism. RESULTS In clinical specimens, the adiponectin receptor AdipoR1 was reduced, and the phosphorylation acetyl-CoA carboxylase (p-ACC) was increased. In vitro and in vivo pathological immunofluorescence and Western blotting confirmed that, under the condition of high glucose, malpighian tubules displayed ectopic lipid deposition and expressed related lipid parameters accompanied by fibrosis. Empagliflozin intervention reduced lipid deposition fibrosis and renal tubular atrophy, and the addition of compound C promoted disease progression. Moreover, siAdipoR1 transfection proved that AdipoR1 affected P-AMPK and then p-ACC affected lipid metabolism in renal tubular cells. CONCLUSION According to the above experimental results, empagliflozin could reduce lipid metabolism of DN through AdipoR1/P-AMPK/P-ACC pathway and delay DN progress.
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Affiliation(s)
- Zhiqin Zhang
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Lihua Ni
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Lian Zhang
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Dongqing Zha
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Chun Hu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Lingli Zhang
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Huiling Feng
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Xiaobao Wei
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
| | - Xiaoyan Wu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of China
- Correspondence: Xiaoyan Wu Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan430071, People’s Republic of ChinaTel +86 15972935798 Email
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Das S, Chattopadhyay D, Chatterjee SK, Mondal SA, Majumdar SS, Mukhopadhyay S, Saha N, Velayutham R, Bhattacharya S, Mukherjee S. Increase in PPARγ inhibitory phosphorylation by Fetuin-A through the activation of Ras-MEK-ERK pathway causes insulin resistance. Biochim Biophys Acta Mol Basis Dis 2020; 1867:166050. [PMID: 33359696 DOI: 10.1016/j.bbadis.2020.166050] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 11/13/2020] [Accepted: 12/14/2020] [Indexed: 12/20/2022]
Abstract
Obesity induced insulin resistance is primarily regulated by the inhibitory phosphorylation of peroxisome proliferator-activated receptor γ at serine 273 (PPARγS273) which has been shown to be regulated by MEK and ERK. An upstream regulatory molecule of this pathway could be a therapeutic option. Here we analyzed the involvement of Fetuin-A (FetA), a key hepato-adipokine implicated in insulin resistance, as an upstream regulator molecule for the regulation of PPARγ inhibitory phosphorylation. Mice fed with standard diet (SD), high fat diet (HFD) and HFD with FetA knockdown (HFD-FetAKD) were used to examine the role of FetA on PPARγS273 phosphorylation in adipocytes. The mechanism of regulation and its effect on skeletal muscle were studied using primary adipocytes, 3T3-L1 (preadipocyte) and C2C12 (myotube) cell lines. Increased FetA in HFD mice strongly correlated with augmentation of PPARγS273 phosphorylation in inflamed adipocytes while knockdown of FetA suppressed it. This effect of FetA was mediated through the activation of Ras which in turn activated MEK and ERK. On addressing how FetA could stimulate activation of Ras, we found that FetA triggered TNFα in inflamed adipocytes which induced Ras activation. The ensuing sharp fall in adiponectin level attenuated AMPK activation in skeletal muscle cells affecting mitochondrial ATP production. Our data reveal the essential role of FetA induced activation of Ras in regulating PPARγ inhibitory phosphorylation through Ras-MEK-ERK pathway which downregulates adiponectin disrupting skeletal muscle mitochondrial bioenergetics. Thus, FetA mediated PPARγ inactivation has adverse consequences upon adipocyte-myocyte crosstalk leading to disruption of energy homeostasis and loss of insulin sensitivity.
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Affiliation(s)
- Snehasis Das
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Dipanjan Chattopadhyay
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Subhendu K Chatterjee
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Samim Ali Mondal
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research-Seth Sukhlal Karnani Memorial (IPGME&R-SSKM) Hospital, Kolkata 700025, India
| | | | - Satinath Mukhopadhyay
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research-Seth Sukhlal Karnani Memorial (IPGME&R-SSKM) Hospital, Kolkata 700025, India
| | - Nirmalendu Saha
- Department of Zoology, North-Eastern Hill University, Shillong 793022, India
| | | | - Samir Bhattacharya
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Sutapa Mukherjee
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India.
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20
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Adafer R, Messaadi W, Meddahi M, Patey A, Haderbache A, Bayen S, Messaadi N. Food Timing, Circadian Rhythm and Chrononutrition: A Systematic Review of Time-Restricted Eating's Effects on Human Health. Nutrients 2020; 12:nu12123770. [PMID: 33302500 PMCID: PMC7763532 DOI: 10.3390/nu12123770] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/04/2020] [Accepted: 12/06/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Recent observations have shown that lengthening the daily eating period may contribute to the onset of chronic diseases. Time-restricted eating (TRE) is a diet that especially limits this daily food window. It could represent a dietary approach that is likely to improve health markers. The aim of this study was to review how time-restricted eating affects human health. METHOD Five general databases and six nutrition journals were screened to identify all studies published between January 2014 and September 2020 evaluating the effects of TRE on human populations. RESULTS Among 494 articles collected, 23 were finally included for analysis. The overall adherence rate to TRE was 80%, with a 20% unintentional reduction in caloric intake. TRE induced an average weight loss of 3% and a loss of fat mass. This fat loss was also observed without any caloric restriction. Interestingly, TRE produced beneficial metabolic effects independently of weight loss, suggesting an intrinsic effect based on the realignment of feeding and the circadian clock. CONCLUSIONS TRE is a simple and well-tolerated diet that generates many beneficial health effects based on chrononutrition principles. More rigorous studies are needed, however, to confirm those effects, to understand their mechanisms and to assess their applicability to human health.
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Affiliation(s)
- Réda Adafer
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Wassil Messaadi
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Mériem Meddahi
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Alexia Patey
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Abdelmalik Haderbache
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Sabine Bayen
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
| | - Nassir Messaadi
- Department of General Medicine, Henri Warembourg Faculty of Medicine, University of Lille, 59000 Lille, France
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21
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Wang K, Zhang B, Song D, Xi J, Hao W, Yuan J, Gao C, Cui Z, Cheng Z. Alisol A Alleviates Arterial Plaque by Activating AMPK/SIRT1 Signaling Pathway in apoE-Deficient Mice. Front Pharmacol 2020; 11:580073. [PMID: 33224034 PMCID: PMC7667245 DOI: 10.3389/fphar.2020.580073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Accepted: 09/09/2020] [Indexed: 12/25/2022] Open
Abstract
Alismatis Rhizoma (zexie), an herb used in traditional Chinese medicine, exhibits hypolipemic, anti-inflammation and anti-atherosclerotic activities. Alisol A is one of the main active ingredients in Alismatis Rhizoma extract. In this study, we investigate the role of alisol A in anti-atherosclerosis (AS). Our study demonstrated that alisol A can effectively inhibit the formation of arterial plaques and blocked the progression of AS in ApoE−/− mice fed with high-fat diet and significantly reduced the expression of inflammatory cytokins in aorta, including ICAM-1, IL-6, and MMP-9. In addition, we found that alisol A increased the expression of PPARα and PPARδ proteins in HepG2 cells and in liver tissue from ApoE−/− mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-κB inhibitor IκBα in HepG2 cells. Our results suggested that alisol A is a multi-targeted agent that exerts anti-atherosclerotic action by regulating lipid metabolism and inhibiting inflammatory cytokine production. Therefore, alisol could be a promising lead compound to develop drugs for the treatment of AS.
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Affiliation(s)
- Ke Wang
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Beibei Zhang
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Dingzhong Song
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Jianqiang Xi
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Wusi Hao
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Jie Yuan
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Chenyu Gao
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Zhongbao Cui
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
| | - Zhihong Cheng
- China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China
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22
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Jiang Z, Yang Z, Zhang H, Yao Y, Ma H. Genistein activated adenosine 5'-monophosphate-activated protein kinase-sirtuin1/peroxisome proliferator-activated receptor γ coactivator-1α pathway potentially through adiponectin and estrogen receptor β signaling to suppress fat deposition in broiler chickens. Poult Sci 2020; 100:246-255. [PMID: 33357687 PMCID: PMC7772704 DOI: 10.1016/j.psj.2020.10.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/15/2020] [Accepted: 10/06/2020] [Indexed: 01/09/2023] Open
Abstract
Genistein can be used as a dietary additive to control fat deposition in animals, while its mechanism is poorly understood. In this study, a total of 144 male broilers were randomly divided into 4 groups. Birds were fed standard diets supplemented with 0, 50, 100 or 150 mg of genistein/kg from 21 to 42 d of age. Results showed that genistein treatment decreased the relative weight of abdominal fat and triglyceride contents in broiler chickens. Genistein downregulated hepatic lipid droplets accumulation and upregulated the activity of lipoprotein lipase and hepatic lipase and the concentration of adiponectin. Furthermore, the liver X receptor α, sterol regulatory element–binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA expressions were decreased, whereas adiponectin receptor 2, peroxisome proliferator-activated receptor α, adipose triglyceride lipase, and carnitine palmitoyl transferase-I (CPT-I) mRNA abundances were increased in the liver of broilers treated with genistein. In addition, genistein increased the NAD+ concentration and NAD+/NADH ratio in the liver. Genistein increased estrogen receptor β (ERβ), forkhead box O1, nicotinamide phosphoribosyl transferase, sirtuin1 (SIRT1), phospho (p)-adenosine 5′-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), p-ACC, and CPT-I protein levels, whereas the SREBP-1c and FAS levels were decreased. These data indicated that genistein might reduce fat accumulation in broiler chickens via activating the AMPK-SIRT1/PGC-1α signaling pathway. The activation of this signaling pathway might be achieved by its direct effect on improving the adiponectin secretion or its indirect effect on upregulation of ERβ expression level through paracrine acting of adiponectin.
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Affiliation(s)
- Zhihao Jiang
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhongmiao Yang
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Huihui Zhang
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yao Yao
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Haitian Ma
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
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23
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Shabalala SC, Dludla PV, Mabasa L, Kappo AP, Basson AK, Pheiffer C, Johnson R. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed Pharmacother 2020; 131:110785. [PMID: 33152943 DOI: 10.1016/j.biopha.2020.110785] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, as it affects up to 30 % of adults in Western countries. Moreover, NAFLD is also considered an independent risk factor for cardiovascular diseases. Insulin resistance and inflammation have been identified as key factors in the pathophysiology of NAFLD. Although the mechanisms associated with the development of NAFLD remain to be fully elucidated, a complex interaction between adipokines and cytokines appear to play a crucial role in the development of this condition. Adiponectin is the most common adipokine known to be inversely linked with insulin resistance, lipid accumulation, inflammation and NAFLD. Consequently, the focus has been on the use of new therapies that may enhance hepatic expression of adiponectin downstream targets or increase the serum levels of adiponectin in the treatment NAFLD. While currently used therapies show limited efficacy in this aspect, accumulating evidence suggest that various dietary polyphenols may stimulate adiponectin levels, offering potential protection against the development of insulin resistance, inflammation and NAFLD as well as associated conditions of metabolic syndrome. As such, this review provides a better understanding of the role polyphenols play in modulating adiponectin signaling to protect against NAFLD. A brief discussion on the regulation of adiponectin during disease pathophysiology is also covered to underscore the potential protective effects of polyphenols against NAFLD. Some of the prominent polyphenols described in the manuscript include aspalathin, berberine, catechins, chlorogenic acid, curcumin, genistein, piperine, quercetin, and resveratrol.
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Affiliation(s)
- Samukelisiwe C Shabalala
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa, 3886, South Africa
| | - Phiwayinkosi V Dludla
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, 60131, Italy
| | - Lawrence Mabasa
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa
| | - Abidemi P Kappo
- Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, 2006, South Africa
| | - Albertus K Basson
- Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa, 3886, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa
| | - Rabia Johnson
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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24
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Wu D, Liu Z, Yu P, Huang Y, Cai M, Zhang M, Zhao Y. Cold stress regulates lipid metabolism via AMPK signalling in Cherax quadricarinatus. J Therm Biol 2020; 92:102693. [PMID: 32888578 DOI: 10.1016/j.jtherbio.2020.102693] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 07/16/2020] [Accepted: 08/05/2020] [Indexed: 12/29/2022]
Abstract
Lipids play an important role in protecting poikilotherms from cold stress, but relatively little is known about the regulation of lipid metabolism under cold stress, especially in crustaceans. In the present study, red-clawed crayfish Cherax quadricarinatus was employed as a model organism. Animals were divided into four temperature groups (25, 20, 15 and 9 °C) and treated for 4 weeks, with the 25 °C group serving as a control. The total lipid content in the hepatopancreas as well as the triglyceride, cholesterol and free fatty acid levels in the hemolymph were determined. Lipids stored in the hepatopancreas and hemolymph decreased with decreasing temperature, with changes in the 9 °C group most pronounced, indicating that lipids are the main energy source for crayfish at low temperatures. Furthermore, enzyme activity of lipase, fatty acid synthase, acetyl-CoA carboxylase, and lipoprotein esterase, and gene expression analysis of fatty acid synthase gene, acetyl-CoA carboxylase gene and carnitine palmitoyltransferase gene showed that the digestion, synthesis and oxidation of lipids in the hepatopancreas were inhibited under low temperature stress, but expression of sphingolipid delta-4 desaturase (DEGS) was increased, indicating an increase in the demand for highly unsaturated fatty acids at low temperatures. Analysis of the expression of genes related to the AMP-activated protein kinase (AMPK) signalling pathway revealed that the adiponectin receptor gene was rapidly upregulated at low temperatures, which may in turn activate the expression of the downstream AMPKα gene, thereby inhibiting lipid anabolism.
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Affiliation(s)
- Donglei Wu
- School of Life Science, East China Normal University, Shanghai, 200241, China; Shanghai Academy of Agricultural Sciences, Shanghai, 201403, China
| | - Zhiquan Liu
- School of Life Science, East China Normal University, Shanghai, 200241, China
| | - Ping Yu
- School of Life Science, East China Normal University, Shanghai, 200241, China
| | - Youhui Huang
- School of Life Science, East China Normal University, Shanghai, 200241, China
| | - Mingqi Cai
- School of Life Science, East China Normal University, Shanghai, 200241, China
| | - Meng Zhang
- School of Life Science, East China Normal University, Shanghai, 200241, China
| | - Yunlong Zhao
- School of Life Science, East China Normal University, Shanghai, 200241, China; State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai, 200241, China.
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25
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Liu YS, Zhang YY, Xing T, Li JL, Wang XF, Zhu XD, Zhang L, Gao F. Glucose and lipid metabolism of broiler chickens fed diets with graded levels of corn resistant starch. Br Poult Sci 2020; 61:599-607. [PMID: 32456457 DOI: 10.1080/00071668.2020.1774511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
1. The aim of this study was to investigate the effects of graded levels of dietary corn resistant starch (RS) on glucose and lipid metabolism of broilers. 2. A total of 320 male broiler chicks (Arbor Acres, one-day-old) were randomly allocated to five dietary treatments, including a corn-soybean control diet, a corn-soybean based diet containing 20% corn starch, and three diets containing 4%, 8% and 12% RS by replacing corn starch with 6.67%, 13.33% and 20% Hi-Maize® 260 (identified as control, RS1, RS2, RS3 and RS4, respectively). Each treatment contained eight replicates with eight birds, and the experiment lasted 42 days. 3. Birds fed RS diets showed lower (P < 0.05) concentrations of serum low-density lipoprotein cholesterol and non-esterified fatty acid (NEFA) at d 21 and 42 of age, compared to the control. Lower (P < 0.05) hepatic apolipoprotein B concentration and citrate synthase (CS) activity, as well as a higher (P < 0.05) glycogen synthase (GS) concentration were observed in birds fed RS diets than those in the control group at d 21 of age. Consuming RS diets linearly increased (P < 0.01) serum glucose concentration, and linearly decreased (P < 0.01) NEFA concentrations in broilers at d 21 and 42 of age. Liver GS concentration and activities of hexokinase, pyruvate and CS were linearly increased (P < 0.01) in broilers at d 21 of age, but were linearly decreased (P < 0.05) in birds at d 42 of age in response to the increase of dietary RS levels. Feeding RS diets linearly decreased (P < 0.05) mRNA expressions of PC, PPARα and CPT-1 at d 21 of age and the mRNA expressions of SREBP-1 c, ChREBP, ACC and FAS at d 42 of age, and linearly increased (P < 0.05) the mRNA expressions of PEPCK, PC, LKB1, AMPKα1, PPARα, CPT-1 and L-FABP at d 42 of age. 4. Feeding broilers with diets containing higher concentration of RS promoted hepatic lipolysis and gluconeogenesis through activated AMPK signalling pathway and accelerated whole-body energy expenditures in the grower phase.
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Affiliation(s)
- Y S Liu
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
| | - Y Y Zhang
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
| | - T Xing
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
| | - J L Li
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
| | - X F Wang
- College of Science, Nanjing Agricultural University , Nanjing, China
| | - X D Zhu
- College of Science, Nanjing Agricultural University , Nanjing, China
| | - L Zhang
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
| | - F Gao
- College of Animal Science and Technology, Jiangsu Provincial Key Laboratory of Animal Origin Food Production and Safety Guarantee, Jiangsu Provincial Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University , Nanjing, China
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26
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Ding H, Li Y, Li W, Tao H, Liu L, Zhang C, Kong T, Feng S, Li J, Wang X, Wu J. Epigallocatechin-3-gallate activates the AMP-activated protein kinase signaling pathway to reduce lipid accumulation in canine hepatocytes. J Cell Physiol 2020; 236:405-416. [PMID: 32572960 DOI: 10.1002/jcp.29869] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 05/16/2020] [Accepted: 05/24/2020] [Indexed: 12/19/2022]
Abstract
Epigallocatechin-3-gallate (EGCG) plays a crucial role in hepatic lipid metabolism. However, the underlying regulatory mechanism of hepatic lipid metabolism by EGCG in canine is unclear. Primary canine hepatocytes were treated with EGCG (0.01, 0.1, or 1 μM) and BML-275 (an AMP-activated protein kinase [AMPK] inhibitor) to study the effects of EGCG on the gene and protein expressions associated with AMPK signaling pathway. Data showed that treatment with EGCG had greater activation of AMPK, as well as greater expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) along with upregulated messenger RNA (mRNA) abundance and protein abundance of PPARα-target genes. EGCG decreased the expression levels and transcriptional activity of sterol regulatory element-binding protein 1c (SREBP-1c) along with downregulated mRNA abundance and protein abundance of SREBP-1c target genes. Of particular interest, exogenous BML-275 could reduce or eliminate the effects of EGCG on lipid metabolism in canine hepatocytes. Furthermore, the content of triglyceride was significantly decreased in the EGCG-treated groups. These results suggest that EGCG might be a potential agent in preventing high-fat diet-induced lipid accumulation in small animals.
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Affiliation(s)
- Hongyan Ding
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Yu Li
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Wei Li
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Huanqing Tao
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Leihong Liu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Cai Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China
| | - Tao Kong
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China
| | - Shibin Feng
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Jinchun Li
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Xichun Wang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Jinjie Wu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
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Henriksson E, Andersen B. FGF19 and FGF21 for the Treatment of NASH-Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human. Front Endocrinol (Lausanne) 2020; 11:601349. [PMID: 33414764 PMCID: PMC7783467 DOI: 10.3389/fendo.2020.601349] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/10/2020] [Indexed: 12/17/2022] Open
Abstract
FGF19 and FGF21 analogues are currently in clinical development for the potential treatment of NASH. In Phase 2 clinical trials analogues of FGF19 and FGF21 decrease hepatic steatosis with up to 70% (MRI-PDFF) after 12 weeks and as early as 12-16 weeks of treatment an improvement in NASH resolution and fibrosis has been observed. Therefore, this class of compounds is currently of great interest in the field of NASH. FGF19 and FGF21 belong to the endocrine FGF19 subfamily and both require the co-receptor beta-klotho for binding and signalling through the FGF receptors. FGF19 is expressed in the ileal enterocytes and is released into the enterohepatic circulation in response to bile acids stimuli and in the liver FGF19 inhibits hepatic bile acids synthesis by transcriptional regulation of Cyp7A1, which is the rate limiting enzyme. FGF21 is, on the other hand, highly expressed in the liver and is released in response to high glucose, high free-fatty acids and low amino-acid supply and regulates energy, glucose and lipid homeostasis by actions in the CNS and in the adipose tissue. FGF19 and FGF21 are differentially expressed, have distinct target tissues and separate physiological functions. It is therefore of peculiar interest to understand why treatment with both FGF19 and FGF21 analogues have strong beneficial effects on NASH parameters in mice and human and whether the mode of action is overlapping This review will highlight the physiological and pharmacological effects of FGF19 and FGF21. The potential mode of action behind the anti-steatotic, anti-inflammatory and anti-fibrotic effects of FGF19 and FGF21 will be discussed. Finally, development of drugs is always a risk benefit analysis and the human relevance of adverse effects observed in pre-clinical species as well as findings in humans will be discussed. The aim is to provide a comprehensive overview of the current understanding of this drug class for the potential treatment of NASH.
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McAllister MJ, Pigg BL, Renteria LI, Waldman HS. Time-restricted feeding improves markers of cardiometabolic health in physically active college-age men: a 4-week randomized pre-post pilot study. Nutr Res 2019; 75:32-43. [PMID: 31955013 DOI: 10.1016/j.nutres.2019.12.001] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 10/14/2019] [Accepted: 12/02/2019] [Indexed: 12/26/2022]
Abstract
Time-restricted feeding (TRF) has been shown to improve body composition, blood lipids, and reduce markers of inflammation and oxidative stress. However, most of these studies come from rodent models and small human samples, and it is not clear if the benefits are dependent upon a caloric deficit, or the time restriction nature of TRF. Based off of previous research, we hypothesized that humans following an ad libitum TRF protocol would reduce caloric intake and this caloric deficit would be associated with greater improvements in cardiometabolic health including blood pressure, body composition, blood lipids, and markers of inflammation and antioxidant status compared to an isocaloric TRF protocol. The purpose of this study was to: (1) examine the impact of TRF on markers of cardio-metabolic health and antioxidant status and (2) determine if the adaptations from TRF would differ under ad libitum compared to isocaloric conditions. Twenty-three healthy men were randomized to either an ad libitum or isocaloric 16:8 (fasting: feeding) TRF protocol. A total of 22 men completed the 28-day TRF protocol (mean ± SD; age: 22 ± 2.5 yrs.; height: 178.4 ± 6.9 cm; weight: 90.3 ± 24 kg; BMI: 28.5 ± 8.3 kg/m2). Fasting blood samples were analyzed for glucose, lipids, as well as adiponectin, human growth hormone, insulin, cortisol, C-reactive protein, superoxide dismutase, total nitrate/nitrite, and glutathione. Time-restricted feeding in both groups was associated with significant (P < .05) reductions in body fat, blood pressure, and significant increases in adiponectin and HDL-c. No changes in caloric intake were detected. In summary, the results from this pilot study in metabolically healthy, active young men, suggest that TRF can improve markers of cardiometabolic health.
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Affiliation(s)
- Matthew J McAllister
- Metabolic and Applied Physiology Lab, Department of Health and Human Performance, Texas State University, San Marcos, TX, 78666.
| | - Brandon L Pigg
- School of Health Studies, The University of Memphis, Memphis TN, 38152
| | - Liliana I Renteria
- Metabolic and Applied Physiology Lab, Department of Health and Human Performance, Texas State University, San Marcos, TX, 78666
| | - Hunter S Waldman
- Human Performance Lab, Department of Kinesiology, University of North Alabama, Florence, AL, 35632
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Jin M, Pan T, Tocher DR, Betancor MB, Monroig Ó, Shen Y, Zhu T, Sun P, Jiao L, Zhou Q. Dietary choline supplementation attenuated high-fat diet-induced inflammation through regulation of lipid metabolism and suppression of NFκB activation in juvenile black seabream ( Acanthopagrus schlegelii). J Nutr Sci 2019; 8:e38. [PMID: 32042405 PMCID: PMC6984006 DOI: 10.1017/jns.2019.34] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 12/18/2022] Open
Abstract
The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Choline
- HFD + C1, HFD + choline (3 g/kg)
- HFD + C2, HFD + choline (6 g/kg)
- HFD + C3, HFD + choline (12 g/kg)
- HFD, high-fat diet
- High-fat diets
- Inflammation
- LPS, lipopolysaccharide
- Lipid metabolism
- NFκB
- accα, acetyl-CoA carboxylase α
- cpt1a, carnitine palmitoyltransferase 1a
- fas, fatty acid synthase
- hsl, hormone-sensitive lipase
- qPCR, quantitative PCR
- srebp-1, sterol regulatory element-binding protein-1
- tgfβ-1, transforming growth factor β-1
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Affiliation(s)
- Min Jin
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Tingting Pan
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Douglas R. Tocher
- Faculty of Natural Sciences, Institute of Aquaculture, University of Stirling, StirlingFK9 4LA, UK
| | - Mónica B. Betancor
- Faculty of Natural Sciences, Institute of Aquaculture, University of Stirling, StirlingFK9 4LA, UK
| | - Óscar Monroig
- Instituto de Acuicultura Torre de la Sal, Consejo Superior de Investigaciones Científicas (IATS-CSIC), 12595 Ribera de Cabanes, Castellón, Spain
| | - Yuedong Shen
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Tingting Zhu
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Peng Sun
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Lefei Jiao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Qicun Zhou
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
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Atashi H, Salavati M, De Koster J, Ehrlich J, Crowe M, Opsomer G, Hostens M. Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows. J Anim Breed Genet 2019; 137:292-304. [PMID: 31576624 PMCID: PMC7217222 DOI: 10.1111/jbg.12442] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/07/2019] [Accepted: 09/12/2019] [Indexed: 12/31/2022]
Abstract
The aim of this study was to identify genomic regions associated with 305‐day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single‐step genomic BLUP approach and imputed high‐density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305‐day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305‐day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and −0.52, respectively. The results identified three windows on BTA14 associated with 305‐day milk yield and the parameters of lactation curve in primi‐ and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes.
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Affiliation(s)
- Hadi Atashi
- Department of Reproduction, Obstetrics and Herd Health, Ghent University, Merelbeke, Belgium.,Department of Animal Science, Shiraz University, Shiraz, Iran
| | - Mazdak Salavati
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK
| | - Jenne De Koster
- Department of Reproduction, Obstetrics and Herd Health, Ghent University, Merelbeke, Belgium
| | | | - Mark Crowe
- University College Dublin, Dublin, Ireland
| | - Geert Opsomer
- Department of Reproduction, Obstetrics and Herd Health, Ghent University, Merelbeke, Belgium
| | | | - Miel Hostens
- Department of Reproduction, Obstetrics and Herd Health, Ghent University, Merelbeke, Belgium
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Zhang J, Zhang SD, Wang P, Guo N, Wang W, Yao LP, Yang Q, Efferth T, Jiao J, Fu YJ. Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells. Eur J Pharmacol 2019; 861:172618. [DOI: 10.1016/j.ejphar.2019.172618] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/15/2019] [Accepted: 08/16/2019] [Indexed: 12/20/2022]
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Ahmad A, Ali T, Kim MW, Khan A, Jo MH, Rehman SU, Khan MS, Abid NB, Khan M, Ullah R, Jo MG, Kim MO. Adiponectin homolog novel osmotin protects obesity/diabetes-induced NAFLD by upregulating AdipoRs/PPARα signaling in ob/ob and db/db transgenic mouse models. Metabolism 2019; 90:31-43. [PMID: 30473057 DOI: 10.1016/j.metabol.2018.10.004] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 10/05/2018] [Accepted: 10/15/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND In metabolic disorders, adiponectin and adiponectin receptors (AdipoR1/R2) signaling has a key role in improving nonalcoholic fatty liver disease (NAFLD) in obesity-associated diabetes. OBJECTIVE To the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of the novel osmotin, a homolog of mammalian adiponectin, against NAFLD in leptin-deficient ob/ob and db/db mice. METHODS The ob/ob and db/db mice were treated with osmotin at a dose of 5 μg/g three times a week for two weeks. To co-relate the in vivo results we used the human liver carcinoma HepG2 cells, subjected to knockdown with small siRNAs of AdipoR1/R2 and PPARα genes and treated with osmotin and palmitic acid (P.A.). MTT assay, Western blotting, immunohistofluorescence assays, and plasma biochemical analyses were applied. RESULTS Osmotin stimulated AdipoR1/R2 and its downstream APPL1/PPAR-α/AMPK/SIRT1 pathways in ob/ob and db/db mice, and HepG2 cells exposed to P.A. Mechanistically, we confirmed that knockdown of AdipoR1/R2 and PPARα by their respective siRNAs abolished the osmotin activity in HepG2 cells exposed to P.A. Overall, the in vivo and in vitro results suggested that osmotin protected against NAFLD through activation of AdipoR1/R2 and its downstream APPL1/PPAR-α/AMPK/SIRT1 pathways as shown by the reduced body weight, blood glucose level and glycated hemoglobin, improved glucose tolerance, attenuated insulin resistance and hepatic glucogenesis, regulated serum lipid parameters, and increased fatty acid oxidation and mitochondrial functions. CONCLUSION Our findings strongly suggest that novel osmotin might be a potential novel therapeutic tool against obesity/diabetes-induced NAFLD and other metabolic disorders.
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MESH Headings
- Adiponectin/analogs & derivatives
- Adiponectin/chemistry
- Animals
- Anti-Obesity Agents/pharmacology
- Cytoprotection/drug effects
- Diabetes Mellitus, Experimental/complications
- Diabetes Mellitus, Experimental/genetics
- Diabetes Mellitus, Experimental/pathology
- Disease Models, Animal
- Hep G2 Cells
- Humans
- Hypoglycemic Agents/pharmacology
- Leptin/deficiency
- Leptin/genetics
- Lipid Metabolism/drug effects
- Liver/drug effects
- Liver/pathology
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Obese
- Mice, Transgenic
- Non-alcoholic Fatty Liver Disease/etiology
- Non-alcoholic Fatty Liver Disease/pathology
- Non-alcoholic Fatty Liver Disease/prevention & control
- Obesity/complications
- Obesity/genetics
- Obesity/pathology
- PPAR alpha/metabolism
- Plant Proteins/pharmacology
- Receptors, Adiponectin/metabolism
- Receptors, Leptin/deficiency
- Receptors, Leptin/genetics
- Signal Transduction/drug effects
- Up-Regulation/drug effects
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Affiliation(s)
- Ashfaq Ahmad
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Tahir Ali
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Min Woo Kim
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Amjad Khan
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Myeung Hoon Jo
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Shafiq Ur Rehman
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Muhammad Sohail Khan
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Noman Bin Abid
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Mehtab Khan
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Rahat Ullah
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Min Gi Jo
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Myeong Ok Kim
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
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Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows. J DAIRY RES 2018; 85:157-162. [PMID: 29785900 DOI: 10.1017/s002202991800016x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.
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Zheng X, Ning C, Zhao P, Feng W, Jin Y, Zhou L, Yu Y, Liu J. Integrated analysis of long noncoding RNA and mRNA expression profiles reveals the potential role of long noncoding RNA in different bovine lactation stages. J Dairy Sci 2018; 101:11061-11073. [PMID: 30268606 DOI: 10.3168/jds.2018-14900] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 08/20/2018] [Indexed: 12/12/2022]
Abstract
Long noncoding RNA (lncRNA) play a critical role in mammary development and breast cancer biology. Despite their important role in the mammary gland, little is known of the roles of lncRNA in bovine lactation, particularly regarding the molecular processes underlying it. To characterize the role of lncRNA in bovine lactation, 4 samples of Holstein cow mammary gland tissue at peak and late lactation stages were examined after biopsy. We then profiled the transcriptome of the mammary gland using RNA sequencing technology. Further, functional lncRNA-mRNA coexpression pairs were constructed to infer the function of lncRNA using a generalized linear model, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. More than 1,000 putative lncRNA were identified, 117 of which were differentially expressed between peak and late lactation stages. Bovine lncRNA were shorter, with fewer exon numbers, and expressed at significantly lower levels than protein-coding genes. Seventy-two differentially expressed (DE) lncRNA were coexpressed with 340 different protein-coding genes. The KEGG pathway analysis showed that target mRNA for DE lncRNA were mainly related to lipid and glucose metabolism, including the peroxisome proliferator-activated receptors and 5' adenosine monophosphate-activated protein kinase signaling pathways. Further bioinformatics and integrative analyses revealed that 12 DE lncRNA potentially played important roles in bovine lactation. Our findings provide a valuable resource for future bovine transcriptome studies, facilitate the understanding of bovine lactation biology, and offer functional information for cattle lactation.
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Affiliation(s)
- X Zheng
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - C Ning
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - P Zhao
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - W Feng
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Y Jin
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - L Zhou
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Y Yu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - J Liu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
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Depreester E, De Koster J, Van Poucke M, Hostens M, Van den Broeck W, Peelman L, Contreras G, Opsomer G. Influence of adipocyte size and adipose depot on the number of adipose tissue macrophages and the expression of adipokines in dairy cows at the end of pregnancy. J Dairy Sci 2018; 101:6542-6555. [DOI: 10.3168/jds.2017-13777] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 02/28/2018] [Indexed: 12/19/2022]
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Song HM, Li X, Liu YY, Lu WP, Cui ZH, Zhou L, Yao D, Zhang HM. Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS. Int J Mol Med 2018; 42:193-207. [PMID: 29620148 PMCID: PMC5979837 DOI: 10.3892/ijmm.2018.3593] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 01/24/2018] [Indexed: 12/22/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage characterized by abnormal hepatic fat accumulation and inflammatory response. Although the molecular mechanisms responsible for the disease are not yet fully understood, the pathogenesis of NAFLD likely involves multiple signals. The identification of effective therapeutic strategies to target these signals is of utmost importance. Carnosic acid (CA), as a phenolic diterpene with anticancer, anti-bacterial, anti-diabetic and neuroprotective properties, is produced by many species of the Lamiaceae family. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in many different cell types. In the present study, wild-type C57BL/6 and MARCKS-deficient mice were randomly divided into the normal chow- or high-fat (HF) diet-fed groups. The HF diet increased the fasting glucose and insulin levels, and promoted glucose intolerance in the wild-type mice. MARCKS deficiency further upregulated intolerance, fasting glucose and insulin. The HF diet also promoted hepatic steatosis, serum alanine transaminase (ALT) and aspartate transaminase (AST) activity, inflammation and lipid accumulation in the wild-type mice. These responses were accelerated in the MARCKS-deficient mice. Importantly, increased inflammation and lipid accumulation were associated with phosphoinositide 3-kinase (PI3K)/AKT, NLR family pyrin domain containing 3 (NLRP3)/nuclear factor-κB (NF-κB) and sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway activation. The mice treated with CA exhibited a significantly improved glucose and insulin tolerance. The production of pro-inflammatory cytokines and lipid accumulation were suppressed by CA. Significantly, MARCKS was reduced in mice fed the HF diet. CA treatment upregulated MARCKS expression compared to the HF group. Furthermore, the activation of the PI3K/AKT, NLRP3/NF-κB and SREBP-1c signaling pathways was inhibited by CA. Taken together, our data suggest that CA suppresses inflammation and lipogenesis in mice fed a HF diet through MARCKS regulation. Thus, CA may be prove to be a useful anti-NAFLD agent.
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Affiliation(s)
- Hong-Mao Song
- Department of Otolaryngology-Head and Neck Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Xiang Li
- Department of Clinical Laboratory, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Yuan-Yuan Liu
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Wei-Ping Lu
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Zhao-Hui Cui
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Li Zhou
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Di Yao
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Hong-Man Zhang
- Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
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Adiponectin: A potential therapeutic target for metabolic syndrome. Cytokine Growth Factor Rev 2018; 39:151-158. [PMID: 29395659 DOI: 10.1016/j.cytogfr.2018.01.004] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Accepted: 01/11/2018] [Indexed: 12/20/2022]
Abstract
Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.
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Du X, Yang Y, Xu C, Peng Z, Zhang M, Lei L, Gao W, Dong Y, Shi Z, Sun X, Wang Z, Li X, Li X, Liu G. Upregulation of miR-181a impairs hepatic glucose and lipid homeostasis. Oncotarget 2017; 8:91362-91378. [PMID: 29207650 PMCID: PMC5710930 DOI: 10.18632/oncotarget.20523] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 08/06/2017] [Indexed: 01/20/2023] Open
Abstract
The contributions of altered post-transcriptional gene silencing to the development of metabolic disorders remain poorly understood thus far. The objective of this study was to evaluate the roles of miR-181a in the regulation of hepatic glucose and lipid metabolism. MiR-181a is abundantly expressed in the liver, and we found that blood and hepatic miR-181a levels were significantly increased in patients and dairy cows with non-alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. We determined that sirtuin1 is a target of miR-181a. Moreover, we found that hepatic sirtuin1 and peroxisome proliferator-activated receptor-γ coactivator-1α expression levels are downregulated, and acetylated peroxisome proliferator-activated receptor-γ coactivator-1α expression levels are upregulated in patients and dairy cows with non-alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. MiR-181a overexpression inhibits the sirtuin1-peroxisome proliferator-activated receptor-γ coactivator-1α pathway, reduces insulin sensitivity, and increases gluconeogenesis and lipid synthesis in dairy cow hepatocytes and HepG2 cells. Conversely, silencing of miR-181a over-activates the sirtuin1-peroxisome proliferator-activated receptor-γ coactivator-1α pathway, increases insulin sensitivity and glycogen content, and decreases gluconeogenesis and lipid synthesis in hepatocytes, even under non-esterified fatty acids treatment conditions. Furthermore, miR-181a overexpression or sirtuin1 knockdown in mice increases lipid accumulation and decreases insulin sensitivity and glycogen content in the liver. Taken together, these findings indicate that increased hepatic miR-181a impairs glucose and lipid homeostasis by silencing sirtuin1 in non-alcoholic fatty liver disease.
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Affiliation(s)
- Xiliang Du
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Yuchen Yang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Chuang Xu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Zhicheng Peng
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Min Zhang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Lin Lei
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Wenwen Gao
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Yuhao Dong
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Zhen Shi
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Xudong Sun
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Zhe Wang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Xiaobing Li
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Xinwei Li
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Guowen Liu
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
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Ravindran S, Kurian GA. The role of secretory phospholipases as therapeutic targets for the treatment of myocardial ischemia reperfusion injury. Biomed Pharmacother 2017; 92:7-16. [DOI: 10.1016/j.biopha.2017.05.042] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 04/27/2017] [Accepted: 05/08/2017] [Indexed: 01/22/2023] Open
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Nie JM, Li HF. Metformin in combination with rosiglitazone contribute to the increased serum adiponectin levels in people with type 2 diabetes mellitus. Exp Ther Med 2017; 14:2521-2526. [PMID: 28962190 PMCID: PMC5609299 DOI: 10.3892/etm.2017.4823] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 07/12/2017] [Indexed: 12/27/2022] Open
Abstract
To evaluate how metformin plus rosiglitazone affect serum adiponectin levels in people suffering from type 2 diabetes mellitus (T2DM), 240 patients having T2DM were selected in this cohort study. Included subjects were randomly and equally separated into three subsets: i) Group A (rosiglitazone group); ii) group B (metformin group); and iii) group C (rosiglitazone + metformin group). Furthermore, meta-analysis of previous studies was performed by searching the general search engines and bibliographic databases. Compared with before treatment, the serum amount of adiponectin grew considerably in the three groups after treatment, and the levels in the group C was much greater than those of groups A and B (all P<0.05). Corresponding meta-analysis results suggested post-treatment serum adiponectin level to be greater than pretreatment level in T2DM patients (P<0.001). Further subgroup analyses indicated that combination therapy of metformin and rosiglitazone may increase the amount of serum adiponectin in T2DM sufferers among the majority subgroups (all P<0.05). The combination of metformin and rosiglitazone treatment increased serum adiponectin levels, suggesting that metformin plus rosiglitazone therapy is a suitable choice to treat T2DM.
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Affiliation(s)
- Jie-Ming Nie
- Department of General Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Hai-Feng Li
- Department of Pharmaceutical Analysis, ALK-Abello A/S Guangzhou Office, Guangzhou, Guangdong 510620, P.R. China
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Metabolomics allows the discrimination of the pathophysiological relevance of hyperinsulinism in obese prepubertal children. Int J Obes (Lond) 2017; 41:1473-1480. [PMID: 28588306 DOI: 10.1038/ijo.2017.137] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 04/23/2017] [Accepted: 05/25/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND/OBJECTIVES Insulin resistance (IR) is the cornerstone of the obesity-associated metabolic derangements observed in obese children. Targeted metabolomics was employed to explore the pathophysiological relevance of hyperinsulinemia in childhood obesity in order to identify biomarkers of IR with potential clinical application. SUBJECTS/METHODS One hundred prepubertal obese children (50 girls/50 boys, 50% IR and 50% non-IR in each group), underwent an oral glucose tolerance test for usual carbohydrate and lipid metabolism determinations. Fasting serum leptin, total and high molecular weight-adiponectin and high-sensitivity C-reactive protein (CRP) levels were measured and the metabolites showing significant differences between IR and non-IR groups in a previous metabolomics study were quantified. Enrichment of metabolic pathways (quantitative enrichment analysis) and the correlations between lipid and carbohydrate metabolism parameters, adipokines and serum metabolites were investigated, with their discriminatory capacity being evaluated by receiver operating characteristic (ROC) analysis. RESULTS Twenty-three metabolite sets were enriched in the serum metabolome of IR obese children (P<0.05, false discovery rate (FDR)<5%). The urea cycle, alanine metabolism and glucose-alanine cycle were the most significantly enriched pathways (PFDR<0.00005). The high correlation between metabolites related to fatty acid oxidation and amino acids (mainly branched chain and aromatic amino acids) pointed to the possible contribution of mitochondrial dysfunction in IR. The degree of body mass index-standard deviation score (BMI-SDS) excess did not correlate with any of the metabolomic components studied. In the ROC analysis, the combination of leptin and alanine showed a high IR discrimination value in the whole cohort (area under curve, AUCALL=0.87), as well as in boys (AUCM=0.84) and girls (AUCF=0.91) when considered separately. However, the specific metabolite/adipokine combinations with highest sensitivity were different between the sexes. CONCLUSIONS Combined sets of metabolic, adipokine and metabolomic parameters can identify pathophysiological relevant IR in a single fasting sample, suggesting a potential application of metabolomic analysis in clinical practice to better identify children at risk without using invasive protocols.
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Park SH, Sung YY, Nho KJ, Kim DS, Kim HK. Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE−∕− via the AMPK Pathway. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2017; 45:757-772. [DOI: 10.1142/s0192415x17500409] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.
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Affiliation(s)
- Sun Haeng Park
- Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
- Department of Korean Medical Scinece, School of Korean Medicine, Pusan National University, Gyeongnam, Yansan 626-870, Republic of Korea
| | - Yoon-Young Sung
- Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
| | - Kyoung jin Nho
- Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
| | - Dong Sun Kim
- KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
| | - Ho Kyoung Kim
- Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea
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De Koster J, Urh C, Hostens M, Van den Broeck W, Sauerwein H, Opsomer G. Relationship between serum adiponectin concentration, body condition score, and peripheral tissue insulin response of dairy cows during the dry period. Domest Anim Endocrinol 2017; 59:100-104. [PMID: 28063290 DOI: 10.1016/j.domaniend.2016.12.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 11/23/2016] [Accepted: 12/03/2016] [Indexed: 12/18/2022]
Abstract
The aim of the present study was to describe the relationship between serum adiponectin concentration and peripheral tissue insulin response in dairy cows with a variable body condition score (BCS) during the dry period. Cows were selected at the beginning of the dry period based on BCS (BCS <3.75, n = 4; BCS >3.75, n = 5). Animals were followed from the beginning of the dry period by weekly blood sampling and assessment of BCS and backfat thickness. Weekly blood samples were analyzed for adiponectin concentration using a bovine specific ELISA. Hyperinsulinemic euglycemic clamp tests were performed at the end of the dry period to measure peripheral tissue insulin response. Insulin dose response curves were established for both glucose and fatty acid metabolism. Regression analysis revealed that the serum concentrations of adiponectin dropped at the end of the dry period (P < 0.05) and were negatively associated with BCS (P < 0.05). At the level of the glucose metabolism, serum concentrations of adiponectin were positively correlated with insulin responsiveness (reflecting the maximal effect of insulin; r = 0.76, P < 0.05), but not with insulin sensitivity (reflecting the insulin concentration needed to achieve halfmaximal effect; r = -0.54, P = 0.13). At the level of the fatty acid metabolism, greater adiponectin concentrations were negatively correlated with lower NEFA levels during the HEC test reflecting the insulin responsiveness of the NEFA metabolism (r = -0.61, P = 0.08), whereas there was no association with the insulin sensitivity of the NEFA metabolism (r = -0.16, P = 0.67). In conclusion, serum concentrations of adiponectin were negatively associated with the BCS of dairy cows during the dry period and positively associated with insulin responsiveness of the glucose and fatty acid metabolism.
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Affiliation(s)
- J De Koster
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
| | - C Urh
- Institute for Animal Science, Physiology and Hygiene Unit, University of Bonn, 53115 Bonn, Germany
| | - M Hostens
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - W Van den Broeck
- Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - H Sauerwein
- Institute for Animal Science, Physiology and Hygiene Unit, University of Bonn, 53115 Bonn, Germany
| | - G Opsomer
- Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common and important chronic liver disease in the world. As the prevalence of obesity increases in adults and children, the incidence of NAFLD has increased rapidly, reaching 17% to 33%. NAFLD is clinically divided into two forms: simple fatty liver (SFL) and non-alcoholic steatohepatitis (NASH), with NASH accounting for 1/3-1/2 of all NAFLD cases. The probability of developing cirrhosis is 0.6%-3.0% in patients with SFL for 10-20 years, and as high as 15%-25% in patients with NASH for 10-15 years. Approximately 1% of cirrhosis cases develop hepatocellular carcinoma each year. The pathogenesis of NAFLD is still not completely clear. It is generally believed that age, sex, obesity, insulin resistance, cytokines, gene polymorphism, and intestinal microflora are involved in the pathogenesis of NAFLD. An in-depth understanding of the pathogenesis of NAFLD can provide a basis for treatment of this disease. In recent years, cytokines or genes have been reported as targets for NAFLD treatment with appreciated effects. Since there is currently no specific treatment for NAFLD, targeted therapy may have a profound impact on the prognosis of the disease.
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Glucagon-like peptide-1 effects lipotoxic oxidative stress by regulating the expression of microRNAs. Biochem Biophys Res Commun 2016; 482:1462-1468. [PMID: 27956176 DOI: 10.1016/j.bbrc.2016.12.058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 12/08/2016] [Indexed: 12/24/2022]
Abstract
Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well. Subsequently, the analysis showed that inhibited expression of miR-33 and miR-370 upregulated the expression of CPT1A and SIRT1, reversely mimics. These results demonstrated for the first time that GLP-1 improve lipotoxic oxidative stress of pancreas by regulate expression of microRNAs.
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Park SH, Sung YY, Jang S, Nho KJ, Choi GY, Kim HK. The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE(-/-) mice. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:352. [PMID: 27608856 PMCID: PMC5016892 DOI: 10.1186/s12906-016-1309-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 08/20/2016] [Indexed: 01/21/2023]
Abstract
Background Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.) Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE−/−) mice. Methods ApoE−/− mice that were fed a high-fat diet (HFD) were treated with DISGT (300 mg/kg/day) or statin (10 mg/kg/day) for 16 weeks. Serum lipid levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase (FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA carboxylase (ACC) in the aorta or liver tissues was measured by western blot analysis. Lipid synthesis and inflammatory responses were assessed by immunohistochemistry and hematoxylin & eosin staining, respectively. Results Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver weight, and the levels of lipids, including total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation, inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC expression in liver tissues. Conclusions The beneficial, anti-lipolytic, and anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a result, the expression of inflammatory factors was reduced. Our data provide evidence that DISGT may have strong therapeutic potential in treating vascular diseases, such as atherosclerosis.
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Piekarski A, Decuypere E, Buyse J, Dridi S. Chenodeoxycholic acid reduces feed intake and modulates the expression of hypothalamic neuropeptides and hepatic lipogenic genes in broiler chickens. Gen Comp Endocrinol 2016; 229:74-83. [PMID: 26965947 DOI: 10.1016/j.ygcen.2016.03.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 02/15/2016] [Accepted: 03/06/2016] [Indexed: 02/03/2023]
Abstract
Bile acids have recently become an emerging research hot spot in mammals due to their roles as metabolic regulators and molecular signatures controlling whole-body metabolic homeostasis. Such effects are still unknown in avian (non-mammalian) species. We, therefore, undertook this study to determine the effect of chenodeoxycholic acid (CDCA) on growth performance and on the expression of hypothalamic neuropeptides and hepatic lipogenic genes in broiler chickens. Chickens fed with diet-containing 0.1% or 0.5% CDCA for two weeks exhibited a significant and a dose dependent reduction of feed intake and body weight compared to the control (standard diet). These changes were accompanied with a significant decrease in plasma glucose levels at d10 and d15 post-treatment. At molecular levels, CDCA treatment significantly up-regulated the expression of feeding-related hypothalamic neuropeptides (NPY, AgRP, ORX, CRH, Ghrl, and MC1R) and down-regulated the hypothalamic expression of SOCS3. CDCA treatment also decreased the mRNA levels of key hepatic lipogenic genes (FAS, ACCα, ME, ATPcl, and SCD-1) and their related transcription factors SREBP-1/2 and PPARα. In addition, CDCA reduced the hepatic expression of FXR and the adipokine, visfatin, and adiponectin genes compared to the control. Together, our data provide evidence that CDCA alters growth performances in broilers and modulates the expression of hypothalamic neuropeptides and hepatic lipogenic and adipocytokine genes.
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Affiliation(s)
- Alissa Piekarski
- Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, United States
| | - Eddy Decuypere
- Division of Livestock-Nutrition-Quality, KUL, 3001 Leuven, Belgium
| | - Johan Buyse
- Division of Livestock-Nutrition-Quality, KUL, 3001 Leuven, Belgium
| | - Sami Dridi
- Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, United States.
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Association of Metabolic Syndrome with the Adiponectin to Homeostasis Model Assessment of Insulin Resistance Ratio. Mediators Inflamm 2015; 2015:607364. [PMID: 26556958 PMCID: PMC4628646 DOI: 10.1155/2015/607364] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 09/20/2015] [Indexed: 01/02/2023] Open
Abstract
This study aimed at determining whether the adiponectin to HOMA-IR (A/H) ratio is associated with MetS and MetS components and comparing the diagnostic efficacy of adiponectin, HOMA-IR, and the A/H ratio in healthy, middle-aged participants. MetS was assessed in 1628 Kazakh participants (men, 768; women, 860). The associations between adiponectin, HOMA-IR, and the A/H ratio with the components of MetS and MetS were examined using logistic regression analysis and receiver operating characteristic (ROC) curves. Our results show that A/H ratio may be a better diagnostic marker for MetS than either HOMA-IR or adiponectin alone, and it may serve as an important biomarker to determine an increased risk for MetS in healthy middle-aged population.
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Khaire A, Rathod R, Kale A, Joshi S. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats. Prostaglandins Leukot Essent Fatty Acids 2015; 99:7-17. [PMID: 26003565 DOI: 10.1016/j.plefa.2015.04.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 04/07/2015] [Accepted: 04/08/2015] [Indexed: 10/23/2022]
Abstract
Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (p<0.01) but reduced docosahexaenoic acid (DHA) (p<0.05), liver mRNA levels of acetyl CoA carboxylase-1 (ACC-1) (p<0.05) and carnitine palmitoyltransferase-1 (CPT-1) (p<0.01) in the offspring. Omega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (p<0.01) and reduced liver mRNA levels of adiponectin, ACC-1, and CPT-1 (p<0.01 for all). Supplementation of both vitamin B12 and omega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.
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Affiliation(s)
- Amrita Khaire
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India
| | - Richa Rathod
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India
| | - Anvita Kale
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India
| | - Sadhana Joshi
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India.
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Weiss M, Bouchoucha S, Aiad F, Ayme-Dietrich E, Dali-Youcef N, Bousquet P, Greney H, Niederhoffer N. Imidazoline-like drugs improve insulin sensitivity through peripheral stimulation of adiponectin and AMPK pathways in a rat model of glucose intolerance. Am J Physiol Endocrinol Metab 2015; 309:E95-104. [PMID: 26015433 DOI: 10.1152/ajpendo.00021.2015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 05/20/2015] [Indexed: 01/04/2023]
Abstract
Altered adiponectin signaling and chronic sympathetic hyperactivity have both been proposed as key factors in the pathogenesis of metabolic syndrome. We recently reported that activation of I1 imidazoline receptors (I1R) improves several symptoms of the metabolic syndrome through sympathoinhibition and increases adiponectin plasma levels in a rat model of metabolic syndrome (Fellmann L, Regnault V, Greney H, et al. J Pharmacol Exp Ther 346: 370-380, 2013). The present study was designed to explore the peripheral component of the beneficial actions of I1R ligands (i.e., sympathoinhibitory independent effects). Aged rats displaying insulin resistance and glucose intolerance were treated with LNP509, a peripherally acting I1R agonist. Glucose tolerance, insulin sensitivity, and adiponectin signaling were assessed at the end of the treatment. Direct actions of the ligand on hepatocyte and adipocyte signaling were also studied. LNP509 reduced the area under the curve of the intravenous glucose tolerance test and enhanced insulin hypoglycemic action and intracellular signaling (Akt phosphorylation), indicating improved glucose tolerance and insulin sensitivity. LNP509 stimulated adiponectin secretion acting at I1R on adipocytes, resulting in increased plasma levels of adiponectin; it also enhanced AMPK phosphorylation in hepatic tissues. Additionally, I1R activation on hepatocytes directly enhanced AMPK phosphorylation. To conclude, I1R ligands can improve insulin sensitivity acting peripherally, independently of sympathoinhibition; stimulation of adiponectin and AMPK pathways at insulin target tissues may account for this effect. This may open a promising new way for the treatment of the metabolic syndrome.
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Affiliation(s)
- Maud Weiss
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Soumaya Bouchoucha
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Farouk Aiad
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Estelle Ayme-Dietrich
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Nassim Dali-Youcef
- Laboratoire de Biochimie Générale et Spécialisée, Hôpitaux Universitaires, Strasbourg, France; and Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, Illkirch, France
| | - Pascal Bousquet
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Hugues Greney
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France
| | - Nathalie Niederhoffer
- Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, France;
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