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Xu X, Yang J, Li Y, Li Y, Zeng X, Chen B. Association of metabolic evaluation of visceral fat score with nonalcoholic fatty liver disease and liver fibrosis: A cross-sectional study based on NHANES. Medicine (Baltimore) 2025; 104:e42213. [PMID: 40295270 PMCID: PMC12040048 DOI: 10.1097/md.0000000000042213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 12/15/2024] [Accepted: 04/04/2025] [Indexed: 04/30/2025] Open
Abstract
The aim of this study was to investigate the correlation between the metabolic evaluation of visceral fat score (METS-VF) with nonalcoholic fatty liver disease (NAFLD) and liver fibrosis within an adolescent population. A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) involving 1274 subjects was conducted. Multiple linear regression was employed to ascertain the association between METS-VF with NAFLD and liver fibrosis. Smoothed curve fitting and threshold effect models were utilized to explore potential nonlinear relationships. Subgroup analyses were conducted to assess the stability of the relationship across different demographic groups. METS-VF exhibited a positive association with both NAFLD and liver fibrosis. In models adjusted for all covariates, the odd ratios (ORs) for METS-VF with NAFLD and liver fibrosis were 15.74 (95% CI: 10.44-23.72) and 1.85 (95% CI: 1.27-2.70), respectively. This positive correlation strengthened with increasing METS-VF when expressed in tertiles (P-value for trend < 0.01). Smoothed curve fitting and threshold effect analysis revealed a nonlinear correlation between METS-VF and NAFLD (log-likelihood ratio [LLR] < 0.01), with a more significant positive correlation observed when METS-VF exceeded 5.75 (OR = 104.42, 95% CI: 17.40-626.58). Similarly, a nonlinear correlation was observed between METS-VF and liver fibrosis (LLR < 0.01), with a stronger positive correlation noted when METS-VF surpassed 4.94 (OR = 34.87, 95% CI: 19.85-64.24). Subgroup analyses by age, ethnicity, and gender indicated that for NAFLD, the positive association with METS-VF was more pronounced in Mexican American female adolescents aged 16 to 19 years, whereas for liver fibrosis, the positive association was stronger in Mexican American female adolescents aged 12 to 16 years. METS-VF was positively associated with the prevalence of NAFLD and hepatic fibrosis in American adolescents. Adolescents with a METS-VF exceeding 5.75 should exercise caution, as higher METS-VF levels may elevate the risk of developing NAFLD and hepatic fibrosis. Additionally, Mexican American female adolescents should be particularly vigilant, as increased METS-VF may heighten the risk of NAFLD and liver fibrosis in this demographic group.
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Affiliation(s)
- Xiaomei Xu
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, Anhui, China
| | - Junping Yang
- Department of General Practice, Wuhu Second People’s Hospital, Wuhu, China
| | - Yuanyuan Li
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, Anhui, China
| | - Yang Li
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, Anhui, China
| | - Xiaoyan Zeng
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, Anhui, China
| | - Biquan Chen
- Department of Infectious Diseases, Anhui Provincial Children’s Hospital, Hefei, Anhui, China
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Huang H, Liu L, Liang Z, Wang Q, Li C, Huang Z, Zhao Z, Han W. C-type natriuretic peptide regulates lipid metabolism through a NPRB-PPAR pathway in the intramuscular and subcutaneous adipocytes in chickens. Sci Rep 2025; 15:13018. [PMID: 40234429 PMCID: PMC12000514 DOI: 10.1038/s41598-025-86433-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/10/2025] [Indexed: 04/17/2025] Open
Abstract
Natriuretic peptides (NPs) have an important role in lipid metabolism in skeletal muscle and adipose tissue in animals. C-type natriuretic peptide (CNP) is an important NP, but the molecular mechanisms that underlie its activity are not completely understood. Treatment of intramuscular fat (IMF) and subcutaneous fat (SCF) adipocytes with CNP led to decreased differentiation, promoted proliferation and lipolysis, and increased the expression of natriuretic peptide receptor B (NPRB) mRNA. Silencing natriuretic peptide C (NPPC) had the opposite results in IMF and SCF adipocytes. Transcriptome analysis found 665 differentially expressed genes (DEGs) in IMF adipocytes and 991 in SCF adipocytes. Seven genes in IMF adipocytes (FABP4, APOA1, ACOX2, ADIPOQ, CD36, FABP5, and LPL) and eight genes in SCF adipocytes (ACOX3, ACSL1, APOA1, CPT1A, CPT2, FABP4, PDPK1 and PPARα) are related to fat metabolism. Fifteen genes were found to be enriched in the peroxisome proliferator-activated receptor (PPAR) pathway. Integrated analysis identified 113 intersection genes in IMF and SCF adipocytes, two of which (APOA1 and FABP4) were enriched in the PPAR pathway. In conclusion, CNP may regulated lipid metabolism through the NPRB-PPAR pathway in both IMF and SCF adipocytes, FABP4 and APOA1 may be the key genes that mediated CNP regulation of fat deposition.
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Affiliation(s)
- Huayun Huang
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Longzhou Liu
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Zhong Liang
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Qianbao Wang
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Chunmiao Li
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Zhengyang Huang
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China
| | - Zhenhua Zhao
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China.
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China.
| | - Wei Han
- Institute of Poultry Science, Chinese Academy of Agriculture Sciences, 225125, Jiangsu, P. R. China.
- College of Animal Science, Yangtze University, Jingzhou, 8060550, P. R. China.
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Kobayashi Y, Yamashita Y, Kimura T, Iwadare T, Okumura T, Wakabayashi SI, Kobayashi H, Sugiura A, Joshita S, Umemura T. Hormone replacement therapy for steatotic liver management after surgical menopause. Clin J Gastroenterol 2025; 18:352-356. [PMID: 39760964 DOI: 10.1007/s12328-024-02090-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 12/18/2024] [Indexed: 01/07/2025]
Abstract
Although steatotic liver onset after natural menopause has been reported, evidence on the clinical course and treatment options for steatotic liver after surgical menopause is scarce. A 34-year-old woman with a history of severe obesity presented to our department with liver dysfunction following total hysterectomy and bilateral oophorectomy. Her serum estradiol level was notably low at 22 pg/mL, and a liver biopsy revealed significant fatty degeneration, lobular inflammation, hepatocyte ballooning, and stage F1 fibrosis. These findings supported a diagnosis of steatotic liver disease following surgical menopause. Subsequent initiation of hormone replacement therapy (HRT) with estrogen led to rapid improvements in liver function and steatotic liver symptoms. Steatotic liver disease should be considered in cases of liver impairment in postoperative menopausal patients, for which HRT represents a promising treatment option.
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Affiliation(s)
- Yoshiaki Kobayashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yuki Yamashita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
- Consultation Center for Liver Diseases, Shinshu University Hospital, Matsumoto, Japan.
| | - Takefumi Kimura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
- Consultation Center for Liver Diseases, Shinshu University Hospital, Matsumoto, Japan
| | - Takanobu Iwadare
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Taiki Okumura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Shun-Ichi Wakabayashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Hiroyuki Kobayashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Ayumi Sugiura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Satoru Joshita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Takeji Umemura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
- Consultation Center for Liver Diseases, Shinshu University Hospital, Matsumoto, Japan
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Cepeda SB, Cutini PH, Valle MI, Campelo AE, Massheimer VL, Sandoval MJ. Bone action of the phytoestrogen genistein under hypoestrogenism and obesity. Mol Cell Endocrinol 2024; 594:112388. [PMID: 39419340 DOI: 10.1016/j.mce.2024.112388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/14/2024] [Accepted: 10/15/2024] [Indexed: 10/19/2024]
Abstract
Osteoporosis and obesity are prevalent diseases in menopause. The phytoestrogen genistein (Gen) is an antioxidant/anti-inflammatory agent proposed as natural therapy to counteract syndromes associated to menopause. In this work we evaluated the bone effect of Gen in a stress environment induced by hypoestrogenism and obesity. Bilaterally ovariectomized female Wistar rats were fed with high-fat diet (obese), or standard diet (non-obese). Osteoblasts (OB) primary cultures from femoral shafts, and retroperitoneal explants of white adipose tissue (WAT) in vitro exposed to Gen were employed as experimental systems. In obese rats, bone oxidative stress revealed by enhancement on H2O2 release, and significant reduction in OB nitric oxide (NO) production, cell growth, alkaline phosphatase activity (ALP), matrix mineralization and collagen deposition was detected. In OB-WAT co-cultures, Gen treatment inhibited H2O2 secretion, and prompted OB differentiation. A direct action of Gen on WAT was demonstrated. The phytoestrogen inhibited H2O2 and TBARS production, and diminished the secretion of the inflammatory adipokine leptin, through a mechanism of action mediated by estrogen receptor (ER) involvement, and MAPK and PI3K signal transduction pathways participation. A directional interaction from WAT to bone was evidenced by the incubation OB with conditioned medium obtained from WAT exposed to Gen (Gen-CM). The presence of Gen-CM improved OB growth, and reduced H2O2 production. The antioxidative effect of Gen on obese bone cells was partially dependent on its ability to reduce leptin secretion by WAT. Altogether, the results suggest that, under obesity, Gen may improve bone metabolism through a direct action on WAT.
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Affiliation(s)
- Sabrina B Cepeda
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina
| | - Pablo H Cutini
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina
| | - María I Valle
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina
| | - Adrián E Campelo
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina
| | - Virginia L Massheimer
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina.
| | - Marisa J Sandoval
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Buenos Aires, Argentina.
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Rossetti CL, Andrade IS, Fonte Boa LF, Neves MB, Fassarella LB, Bertasso IM, Souza MDGCD, Bouskela E, Lisboa PC, Takyia CM, Trevenzoli IH, Fortunato RS, Carvalho DPD. Liraglutide prevents body and fat mass gain in ovariectomized Wistar rats. Mol Cell Endocrinol 2024; 594:112374. [PMID: 39306226 DOI: 10.1016/j.mce.2024.112374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 09/03/2024] [Accepted: 09/18/2024] [Indexed: 09/29/2024]
Abstract
Estrogens exert beneficial metabolic effects by reducing food intake and enhancing energy expenditure through both central and peripheral mechanisms. The decrease of estrogen, as occurs in ovariectomy (OVX), leads to metabolic disturbances, such as increased body weight, adipose tissue mass, basal blood glucose, and impaired glucose tolerance. These effects can be reversed by reintroducing estrogen. GLP-1 and its receptor agonists, known for their antihyperglycemic properties, also exhibit anorexigenic effects. Besides that, research indicates that GLP-1 analogs can induce metabolic changes peripherally, such as increased fatty acid oxidation and inhibited lipogenesis. Given the shared metabolic actions of GLP-1 and estrogens, we explored whether liraglutide, a GLP-1 agonist, could mitigate the metabolic effects of estrogen deficiency. We tested this hypothesis using ovariectomized rats, a model that simulates menopausal estrogen deficiency, and treated them with either liraglutide or 17β-Estradiol benzoate for 21 days. Ovariectomy resulted in elevated DPP-IV activity in both plasma and inguinal white adipose tissue (iWAT). While estrogen replacement effectively countered the DPP-IV increase in both plasma and iWAT, liraglutide only prevented the rise in iWAT DPP-IV activity. Liraglutide prevented body weight and fat mass gain after ovariectomy to the same extent as estradiol treatment. This can be explained by the lower food intake and food efficiency caused by estradiol and liraglutide. However, liraglutide was associated with increased pro-inflammatory cytokines and inflammatory cells in white adipose tissue. Further research is crucial to fully understand the potential benefits and risks of using GLP-1 receptor agonists in the context of menopause.
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Affiliation(s)
- Camila Lüdke Rossetti
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, USA
| | - Iris Soares Andrade
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luiz Fernando Fonte Boa
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcelo Barbosa Neves
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Larissa Brito Fassarella
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Iala Milene Bertasso
- Laboratorio de Fisiologia Endócrina, Instituto de Biologia, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria das Graças Coelho de Souza
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Eliete Bouskela
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Patrícia Cristina Lisboa
- Laboratorio de Fisiologia Endócrina, Instituto de Biologia, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Christina Maeda Takyia
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil; Programa de Pós-Graduação em Ciências Cirúrgicas, Faculdade de Medicina, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Isis Hara Trevenzoli
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rodrigo Soares Fortunato
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Denise Pires de Carvalho
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
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Oliveira THCD, Gonçalves GKN. Effect of ovariectomy and high-fat diet on the expression of estrogen receptors and adipose tissue metabolism in wistar rats. Mol Cell Endocrinol 2024; 592:112327. [PMID: 38996834 DOI: 10.1016/j.mce.2024.112327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/05/2024] [Accepted: 07/06/2024] [Indexed: 07/14/2024]
Abstract
This study addresses the increasing prevalence of obesity, especially among postmenopausal. Estrogen plays a crucial role in regulating adipose tissue in women, with its absence after menopause associated with metabolic complications. The study aimed to determine the lipolytic activity in different adipose tissue depots of ovariectomized rats submitted to a high-fat diet. Also, to analyze the expression of estrogen receptors in adipose tissues and perform histological and morphometric analyzes of these deposits. Female rats were ovariectomized (O) or sham operated (S). The animals were divided into groups: ovariectomized with high-fat diet (OF), sham-operated with high-fat diet (SF), ovariectomized with control diet (OC) or sham-operated with control diet as the control group (SC). After 24 weeks of consuming the diets, rats were killed and adipose tissue deposits were removed. Polymerase chain reaction was performed to analyze the expression of estrogen receptors in adipose tissues, lipolysis assay and histological analysis. Both the high-fat diet and ovariectomy increased body weight and adiposity. There was hypertrophy of adipocytes. Estrogen replacement therapy modulate lipolytic activity in different adipose depots, with different responses in relation to estrogen receptors. Estrogen receptor expression varied between fat depots. Mesenteric adipose tissue showed greater sensitivity to estrogen compared with others. Estrogen increased lipolytic activity in some fat depots, reducing in others. Expression of ERs depends of hormonal status and adipose tissue location, which may explain distinct actions of estrogen on the metabolism of adipose tissue and on the production of adipokines by them.
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Xega V, Liu JL. Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health. MEDICAL REVIEW (2021) 2024; 4:284-300. [PMID: 39135604 PMCID: PMC11317208 DOI: 10.1515/mr-2024-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 05/07/2024] [Indexed: 08/15/2024]
Abstract
This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.
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Affiliation(s)
- Viktoria Xega
- MeDiC Program, The Research Institute of McGill University Health Centre, Montreal, Canada
| | - Jun-Li Liu
- Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Canada
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Wei F, Hughes M, Omer M, Ngo C, Pugazhendhi AS, Kolanthai E, Aceto M, Ghattas Y, Razavi M, Kean TJ, Seal S, Coathup M. A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2308698. [PMID: 38477537 PMCID: PMC11151083 DOI: 10.1002/advs.202308698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Indexed: 03/14/2024]
Abstract
By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)-induced osteoporosis. Results confirm OVX-induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole-body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor-BB and leukemia inhibitory factor, with downregulation of interleukin-1 R6, and receptor activator of nuclear factor kappa-B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor-beta/SMAD, and Wingless-related integration site/be-catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo-osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX-induced bone loss.
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Affiliation(s)
- Fei Wei
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
| | - Megan Hughes
- School of BiosciencesCardiff UniversityWalesCF10 3ATUK
| | - Mahmoud Omer
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
| | - Christopher Ngo
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | | | - Elayaraja Kolanthai
- Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC)University of Central FloridaOrlandoFL32826USA
| | - Matthew Aceto
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Yasmine Ghattas
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Mehdi Razavi
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Thomas J Kean
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Sudipta Seal
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
- Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC)University of Central FloridaOrlandoFL32826USA
| | - Melanie Coathup
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
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Chiang YTT, Kassotis CD. Molecular Assessment of Proadipogenic Effects for Common-Use Contraceptives and Their Mixtures. Endocrinology 2024; 165:bqae050. [PMID: 38648498 PMCID: PMC11081078 DOI: 10.1210/endocr/bqae050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/12/2024] [Accepted: 04/18/2024] [Indexed: 04/25/2024]
Abstract
Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the United States, approximately 65% of reproductive-aged women are estimated to be using contraceptive options, with approximately 33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential effect on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects. As such, the goals of this study were to assess the adipogenic activity of common hormonal contraceptive chemicals and their mixtures. Five different models of adipogenesis were used to provide a rigorous assessment of metabolism-disrupting effects. Interestingly, every individual contraceptive (both estrogens and progestins) and each mixture promoted significant adipogenesis (eg, triglyceride accumulation and/or preadipocyte proliferation). These effects appeared to be mediated in part through estrogen receptor signaling, particularly for the contraceptive mixtures, as cotreatment with fulvestrant acted to inhibit contraceptive-mediated proadipogenic effects on triglyceride accumulation. In conclusion, this research provides valuable insights into the complex interactions between hormonal contraceptives and adipocyte development. The results suggest that both progestins and estrogens within these contraceptives can influence adipogenesis, and the specific effects may vary based on the receptor disruption profiles. Further research is warranted to establish translation of these findings to in vivo models and to further assess causal mechanisms underlying these effects.
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Affiliation(s)
- Yu-Ting Tiffany Chiang
- Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, USA
| | - Christopher D Kassotis
- Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, USA
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Valle MI, Cutini PH, Cepeda SB, Campelo AE, Sandoval MJ, Massheimer VL. Direct in vitro action of estrone on uterine and white adipose tissue in obesity. Mol Cell Endocrinol 2024; 583:112142. [PMID: 38154755 DOI: 10.1016/j.mce.2023.112142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 12/30/2023]
Abstract
The hypothesis whether estrone (E1) could exhibit a direct action at uterus and white adipose tissue (WAT), under obesity was tested. In uterine tissue of obese rats, E1 increased nitric oxide (NO) synthesis, and reduced reactive oxygen species (ROS) production. The anti-oxidative action of E1 was sustained under inflammatory stress or high glucose levels. ICI 182780 or G15 compounds were employed as ER or GPER antagonists respectively. The action of E1 on ROS release involved ER participation; instead GPER mediated the acute stimulation on NO production. The antioxidative effect depends on NO-ROS balance. NO synthase (NOS) blockage suppressed the reduction in ROS synthesis elicited by E1, effect mediated by cNOS and not by iNOS. On WAT explants, E1 reduced ROS and thiobarbituric acid reactive substances production, and diminished leptin release. In summary, the data provide evidence that, in uterus and WAT, E1 counteracts inflammatory and oxidative stress induced by obesity.
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Affiliation(s)
- María Ivone Valle
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina
| | - Pablo H Cutini
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina
| | - Sabrina B Cepeda
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Adrián E Campelo
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Bioterio Del Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional Del Sur (UNS), Bahía Blanca, Argentina
| | - Marisa J Sandoval
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina
| | - Virginia L Massheimer
- Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina.
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11
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de Sousa É, de Mendonça M, Bolin AP, de Oliveira NP, Real CC, Hu X, Huang ZP, Wang DZ, Rodrigues AC. Sex-specific regulation of miR-22 and ERα in white adipose tissue of obese dam's female offspring impairs the early postnatal development of functional beige adipocytes in mice. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167057. [PMID: 38331111 DOI: 10.1016/j.bbadis.2024.167057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 12/31/2023] [Accepted: 01/30/2024] [Indexed: 02/10/2024]
Abstract
During inguinal adipose tissue (iWAT) ontogenesis, beige adipocytes spontaneously appear between postnatal 10 (P10) and P20 and their ablation impairs iWAT browning capacity in adulthood. Since maternal obesity has deleterious effects on offspring iWAT function, we aimed to investigate its effect in spontaneous iWAT browning in offspring. Female C57BL/6 J mice were fed a control or obesogenic diet six weeks before mating. Male and female offspring were euthanized at P10 and P20 or weaned at P21 and fed chow diet until P60. At P50, mice were treated with saline or CL316,243, a β3-adrenoceptor agonist, for ten days. Maternal obesity induced insulin resistance at P60, and CL316,243 treatment effectively restored insulin sensitivity in male but not female offspring. This discrepancy occurred due to female offspring severe browning impairment. During development, the spontaneous iWAT browning and sympathetic nerve branching at P20 were severely impaired in female obese dam's offspring but occurred normally in males. Additionally, maternal obesity increased miR-22 expression in the iWAT of male and female offspring during development. ERα, a target and regulator of miR-22, was concomitantly upregulated in the male's iWAT. Next, we evaluated miR-22 knockout (KO) offspring at P10 and P20. The miR-22 deficiency does not affect spontaneous iWAT browning in females and, surprisingly, anticipates iWAT browning in males. In conclusion, maternal obesity impairs functional iWAT development in the offspring in a sex-specific way that seems to be driven by miR-22 levels and ERα signaling. This impacts adult browning capacity and glucose homeostasis, especially in female offspring.
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Affiliation(s)
- Érica de Sousa
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Mariana de Mendonça
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Anaysa Paola Bolin
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Nayara Preste de Oliveira
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | | | - Xiaoyun Hu
- Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Zhan-Peng Huang
- Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Da-Zhi Wang
- Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Alice Cristina Rodrigues
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
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12
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Frangione B, Birk S, Benzouak T, Rodriguez-Villamizar LA, Karim F, Dugandzic R, Villeneuve PJ. Exposure to perfluoroalkyl and polyfluoroalkyl substances and pediatric obesity: a systematic review and meta-analysis. Int J Obes (Lond) 2024; 48:131-146. [PMID: 37907715 PMCID: PMC10824662 DOI: 10.1038/s41366-023-01401-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 09/22/2023] [Accepted: 10/10/2023] [Indexed: 11/02/2023]
Abstract
INTRODUCTION Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are potentially obesogenic for children. We undertook a systematic review to synthesize this literature and explore sources of heterogeneity in previously published epidemiological studies. METHODS Studies that collected individual-level PFAS and anthropometric data from children up to 12 years of age were identified by searching six databases. We excluded studies that only evaluated obesity measures at the time of birth. A full-text review and quality assessment of the studies was performed using the Office of Health Assessment and Translation (OHAT) criteria. Forest plots were created to summarize measures of association and assess heterogeneity across studies by chemical type and exposure timing. Funnel plots were used to assess small-study effects. RESULTS We identified 24 studies, of which 19 used a cohort design. There were 13 studies included in the meta-analysis examining various chemicals and outcomes. Overall prenatal exposures to four different types of PFAS were not statistically associated with changes in body mass index (BMI) or waist circumference. In contrast, for three chemicals, postnatal exposures were inversely related to changes in BMI (i.e., per log10 increase in PFOS: BMI z-score of -0.16 (95% CI: -0.22, -0.10)). There was no substantial heterogeneity in the reported measures of association within prenatal and postnatal subgroups. We observed modest small-study effects, but correction for these effects using the Trim and Fill method did not change our summary estimate(s). CONCLUSION Our review found no evidence of a positive association between prenatal PFAS exposure and pediatric obesity, whereas an inverse association was found for postnatal exposure. These findings should be interpreted cautiously due to the small number of studies. Future research that can inform on the effects of exposure mixtures, the timing of the exposure, outcome measures, and the shape of the exposure-response curve is needed.
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Affiliation(s)
- Brianna Frangione
- Department of Neuroscience, Carleton University, K1S 5B6, Ottawa, Canada
| | - Sapriya Birk
- Department of Neuroscience, Carleton University, K1S 5B6, Ottawa, Canada
| | - Tarek Benzouak
- Faculty of Medicine, McGill University, H3A 0G4, Montreal, Canada
| | - Laura A Rodriguez-Villamizar
- Department of Neuroscience, Carleton University, K1S 5B6, Ottawa, Canada
- Faculty of Health, Universidad Industrial de Santander, 680002, Bucaramanga, Colombia
| | - Fatima Karim
- Department of Neuroscience, Carleton University, K1S 5B6, Ottawa, Canada
| | | | - Paul J Villeneuve
- Department of Neuroscience, Carleton University, K1S 5B6, Ottawa, Canada.
- CHAIM Research Centre, Carleton University, K1S 5B6, Ottawa, Canada.
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13
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Wang X, Li N, Zheng M, Yu Y, Zhang S. Acetylation and deacetylation of histone in adipocyte differentiation and the potential significance in cancer. Transl Oncol 2024; 39:101815. [PMID: 37935080 PMCID: PMC10654249 DOI: 10.1016/j.tranon.2023.101815] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/17/2023] [Accepted: 10/22/2023] [Indexed: 11/09/2023] Open
Abstract
Adipocytes are derived from pluripotent mesenchymal stem cells and can develop into several cell types including adipocytes, myocytes, chondrocytes, and osteocytes. Adipocyte differentiation is regulated by a variety of transcription factors and signaling pathways. Various epigenetic factors, particularly histone modifications, play key roles in adipocyte differentiation and have indispensable functions in altering chromatin conformation. Histone acetylases and deacetylases participate in the regulation of protein acetylation, mediate transcriptional and post-translational modifications, and directly acetylate or deacetylate various transcription factors and regulatory proteins. The adipocyte differentiation of stem cells plays a key role in various metabolic diseases. Cancer stem cells(CSCs) play an important function in cancer metastasis, recurrence, and drug resistance, and have the characteristics of stem cells. They are expressed in various cell lineages, including adipocytes. Recent studies have shown that cancer stem cells that undergo epithelial-mesenchymal transformation can undergo adipocytic differentiation, thereby reducing the degree of malignancy. This opens up new possibilities for cancer treatment. This review summarizes the regulation of acetylation during adipocyte differentiation, involving the functions of histone acetylating and deacetylating enzymes as well as non-histone acetylation modifications. Mechanistic studies on adipogenesis and acetylation during the differentiation of cancer cells into a benign cell phenotype may help identify new targets for cancer treatment.
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Affiliation(s)
- Xiaorui Wang
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Na Li
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Minying Zheng
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Yongjun Yu
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Shiwu Zhang
- Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China.
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14
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McCall KD, Walter D, Patton A, Thuma JR, Courreges MC, Palczewski G, Goetz DJ, Bergmeier S, Schwartz FL. Anti-Inflammatory and Therapeutic Effects of a Novel Small-Molecule Inhibitor of Inflammation in a Male C57BL/6J Mouse Model of Obesity-Induced NAFLD/MAFLD. J Inflamm Res 2023; 16:5339-5366. [PMID: 38026235 PMCID: PMC10658948 DOI: 10.2147/jir.s413565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 10/31/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic (dysfunction) associated fatty liver disease (MAFLD), is the most common chronic liver disease in the United States. Presently, there is an intense and ongoing effort to identify and develop novel therapeutics for this disease. In this study, we explored the anti-inflammatory activity of a new compound, termed IOI-214, and its therapeutic potential to ameliorate NAFLD/MAFLD in male C57BL/6J mice fed a high fat (HF) diet. Methods Murine macrophages and hepatocytes in culture were treated with lipopolysaccharide (LPS) ± IOI-214 or DMSO (vehicle), and RT-qPCR analyses of inflammatory cytokine gene expression were used to assess IOI-214's anti-inflammatory properties in vitro. Male C57BL/6J mice were also placed on a HF diet and treated once daily with IOI-214 or DMSO for 16 weeks. Tissues were collected and analyzed to determine the effects of IOI-214 on HF diet-induced NAFL D/MAFLD. Measurements such as weight, blood glucose, serum cholesterol, liver/serum triglyceride, insulin, and glucose tolerance tests, ELISAs, metabolomics, Western blots, histology, gut microbiome, and serum LPS binding protein analyses were conducted. Results IOI-214 inhibited LPS-induced inflammation in macrophages and hepatocytes in culture and abrogated HF diet-induced mesenteric fat accumulation, hepatic inflammation and steatosis/hepatocellular ballooning, as well as fasting hyperglycemia without affecting insulin resistance or fasting insulin, cholesterol or TG levels despite overall obesity in vivo in male C57BL/6J mice. IOI-214 also decreased systemic inflammation in vivo and improved gut microbiota dysbiosis and leaky gut. Conclusion Combined, these data indicate that IOI-214 works at multiple levels in parallel to inhibit the inflammation that drives HF diet-induced NAFLD/MAFLD, suggesting that it may have therapeutic potential for NAFLD/MAFLD.
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Affiliation(s)
- Kelly D McCall
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
| | - Debra Walter
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Ashley Patton
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Jean R Thuma
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | - Maria C Courreges
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | | | - Douglas J Goetz
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
- Department of Chemical & Biomolecular Engineering, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
| | - Stephen Bergmeier
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
- Department of Chemistry & Biochemistry, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Frank L Schwartz
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
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15
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Qu J, Wu D, Ko CW, Zhu Q, Liu M, Tso P. Deficiency of apoA-IV in Female 129X1/SvJ Mice Leads to Diet-Induced Obesity, Insulin Resistance, and Decreased Energy Expenditure. Nutrients 2023; 15:4655. [PMID: 37960308 PMCID: PMC10650794 DOI: 10.3390/nu15214655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/23/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage adversely affects contraception, fertility, maternal well-being, and the health of their offspring. Being a major protein component in chylomicrons and high-density lipoproteins, apolipoprotein A-IV (apoA-IV) is involved in lipid metabolism, food intake, glucose homeostasis, prevention against atherosclerosis, and platelet aggregation. The goal of the present study is to determine the impact of apoA-IV deficiency on metabolic functions in 129X1/SvJ female mouse strain. After chronic high-fat diet feeding, apoA-IV-/- mice gained more weight with a higher fat percentage than wild-type (WT) mice, as determined by measuring their body composition. Increased adiposity and adipose cell size were also observed with a microscope, particularly in periovarian fat pads. Based on plasma lipid and adipokine assays, we found that obesity in apoA-IV-/- mice was not associated with hyperlipidemia but with higher leptin levels. Compared to WT mice, apoA-IV deficiency displayed glucose intolerance and elevated insulin levels, according to the data of the glucose tolerance test, and increased HOMA-IR values at fasting, suggesting possible insulin resistance. Lastly, we found obesity in apoA-IV-/- mice resulting from reduced energy expenditure but not food intake. Together, we established a novel and excellent female mouse model for future mechanistic study of obesity and its associated comorbidities.
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Affiliation(s)
- Jie Qu
- Medpace Reference Laboratories, LLC, 5365 Medpace Way, Cincinnati, OH 45227, USA;
| | - Dong Wu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China;
| | - Chih-Wei Ko
- Chroma Medicine, 201 Brookline Ave, Suite 1101, Boston, MA 02215, USA;
| | - Qi Zhu
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA; (Q.Z.); (M.L.)
| | - Min Liu
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA; (Q.Z.); (M.L.)
| | - Patrick Tso
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA; (Q.Z.); (M.L.)
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16
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Bardhi O, Palmer BF, Clegg DJ. The evolutionary impact and influence of oestrogens on adipose tissue structure and function. Philos Trans R Soc Lond B Biol Sci 2023; 378:20220207. [PMID: 37482787 PMCID: PMC10363706 DOI: 10.1098/rstb.2022.0207] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 06/06/2023] [Indexed: 07/25/2023] Open
Abstract
Oestrogens are sex steroid hormones that have gained prominence over the years owing to their crucial roles in human health and reproduction functions which have been preserved throughout evolution. One of oestrogens actions, and the focus of this review, is their ability to determine adipose tissue distribution, function and adipose tissue 'health'. Body fat distribution is sexually dimorphic, affecting males and females differently. These differences are also apparent in the development of the metabolic syndrome and other chronic conditions where oestrogens are critical. In this review, we summarize the different molecular mechanisms, pathways and resulting pathophysiology which are a result of oestrogens actions in and on adipose tissues. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.
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Affiliation(s)
- Olgert Bardhi
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Biff F. Palmer
- Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Deborah J. Clegg
- Vice President for Research, Texas Tech Health Sciences Center, El Paso, TX 75390, USA
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17
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Lu Y, Yuan D, Pan J, Fang X, Ding M, Lu K, Ge X, Qu H, Ma R, Zhang L, Xu H, Wang X, Jiang Y. Dyslipidemia in the first 100 days and the association with acute graft-versus-host disease after allogeneic stem cell transplantation: A single-center retrospective study in China. Transpl Immunol 2023; 78:101829. [PMID: 36972854 DOI: 10.1016/j.trim.2023.101829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 03/23/2023] [Accepted: 03/23/2023] [Indexed: 03/28/2023]
Abstract
Dyslipidemia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The interaction between post-transplant hyperlipidemia and acute graft-versus-host disease (aGVHD) is uncertain. In this study, we performed a retrospective study to explore the relationship between dyslipidemia and aGVHD and the potential mechanism of aGVHD on dyslipidemia in 147 recipients who underwent allo-HSCT. The lipid profiles, transplantation details, and other laboratory data of the subjects were collected in the first 100 days post-transplantation. Our results indicated 63 patients with new-onset hypertriglyceridemia and 39 patients with new-onset hypercholesterolemia. A total of 57 (38.8%) patients developed aGVHD after transplantation. In a multifactorial analysis, aGVHD was an independent factor in the development of dyslipidemia in recipients (P < 0.05). After transplantation, the median LDL-C level of patients with aGVHD was 3.04 mmol/L (standard deviation value (SD): 1.36 mmol/L, 95% confidence interval (CI): 2.62, 3.45 mmol/L), and the LDL-C level in patients without aGVHD was 2.51 mmol/L (SD: 1.38 mmol/L, CI: 2.67, 3.40 mmol/L) (P < 0.05). Female recipients had higher lipid levels than males (P < 0.05). LDL levels (≥ 3.4 mmol/L) post-transplant were an independent risk factor for the development of aGVHD (OR = 0.311, P < 0.05). In conclusion, larger sample studies are anticipated to confirm our preliminary result, and an accurate mechanism between lipid metabolism and aGVHD needs to be determined in the future.
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Affiliation(s)
- Yingxue Lu
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Dai Yuan
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Jie Pan
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Xiaosheng Fang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Mei Ding
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Kang Lu
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Xueling Ge
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Huiting Qu
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Rongqiang Ma
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Lingyan Zhang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Hongzhi Xu
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
| | - Xin Wang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China; Department of Hematology, Shandong Provincial Hospital, Shandong University, Shandong, China
| | - Yujie Jiang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China; Department of Hematology, Shandong Provincial Hospital, Shandong University, Shandong, China.
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18
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Horkeby K, Farman HH, Movérare-Skrtic S, Lionikaite V, Wu J, Henning P, Windahl S, Sjögren K, Ohlsson C, Lagerquist MK. Phosphorylation of S122 in ERα is important for the skeletal response to estrogen treatment in male mice. Sci Rep 2022; 12:22449. [PMID: 36575297 PMCID: PMC9794719 DOI: 10.1038/s41598-022-26939-9] [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: 11/04/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Estrogen receptor alpha (ERα) signaling has beneficial skeletal effects in males. ERα signaling also affects other tissues, and to find bone-specific treatments, more knowledge regarding tissue-specific ERα signaling is needed. ERα is subjected to posttranslational modifications, including phosphorylation, which can influence ERα function in a tissue-specific manner. To determine the importance of phosphorylation site S122 (corresponding to human ERα site S118) for the skeleton and other tissues, male mice with a S122A mutation were used. Total areal bone mineral density was similar between gonadal intact S122A and WT littermates followed up to 12 months of age, and weights of estrogen-responsive organs normalized for body weight were unchanged between S122A and WT males at both 3 and 12 months of age. Interestingly, 12-month-old S122A males had decreased body weight compared to WT. To investigate if site S122 affects the estrogen response in bone and other tissues, 12-week-old S122A and WT males were orchidectomized (orx) and treated with estradiol (E2) or placebo pellets for four weeks. E2 increased cortical thickness in tibia in both orx WT (+ 60%, p < 0.001) and S122A (+ 45%, p < 0.001) males. However, the E2 effect on cortical thickness was significantly decreased in orx S122A compared to WT mice (- 24%, p < 0.05). In contrast, E2 affected trabecular bone and organ weights similarly in orx S122A and WT males. Thus, ERα phosphorylation site S122 is required for a normal E2 response specifically in cortical bone in male mice, a finding that may have implications for development of future treatments against male osteoporosis.
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Affiliation(s)
- Karin Horkeby
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Helen H. Farman
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Sofia Movérare-Skrtic
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Vikte Lionikaite
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Jianyao Wu
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Petra Henning
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Sara Windahl
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden ,grid.4714.60000 0004 1937 0626Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden
| | - Klara Sjögren
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
| | - Claes Ohlsson
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden ,grid.1649.a000000009445082XDepartment of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Marie K. Lagerquist
- grid.8761.80000 0000 9919 9582Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45 Göteborg, Sweden
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19
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Shah P, Patel V, Ashkar M. De novo non-alcoholic fatty liver disease after pancreatectomy: A systematic review. World J Clin Cases 2022; 10:12946-12958. [PMID: 36569000 PMCID: PMC9782952 DOI: 10.12998/wjcc.v10.i35.12946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/10/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these patients as we continue to learn more about post-operative complications. Although pancreatic endocrine and exocrine insufficiencies are known complications of pancreatectomy, increased longevity of these patients has also led to a higher incidence of de novo fatty liver disease which differs from traditional fatty liver disease given the lack of metabolic syndrome. AIM To identify and summarize patterns and risk factors of post-pancreatectomy de novo fatty liver disease to guide future management. METHODS We performed a database search on PubMed selecting papers published between 2001 and 2022 in the English language. PubMed was last accessed 1 June 2022. RESULTS Various factors influence the development of de novo fatty liver including indication for surgery (benign vs malignant), type of pancreatectomy, amount of pancreas remnant, and peri-operative nutritional status. With an incidence rate up to 75%, de novo non-alcoholic fatty liver disease (NAFLD) can develop within 12 mo after pancreatectomy and various risk factors have been established including pancreatic resection line and remnant pancreas volume, peri-operative malnutrition and weight loss, pancreatic exocrine insufficiency (EPI), malignancy as the indication for surgery, and postmenopausal status. CONCLUSION Since majority of risk factors leads to EPI and malnutrition, peri-operative focus on nutrition and enzymes replacement is key in preventing and treating de novo NAFLD after pancreatectomy.
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Affiliation(s)
- Parth Shah
- Gastroenterology, Washington University in Saint Louis, Saint Louis, MO 63110, United States
| | - Vanisha Patel
- Internal Medicine, Washington University in Saint Louis, Saint Louis, MO 63110, United States
| | - Motaz Ashkar
- Gastroenterology, Washington University in Saint Louis, Saint Louis, MO 63110, United States
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20
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He Y, Liang B, Hung SW, Zhang R, Xu H, Chung JPW, Wang CC. Re-evaluation of mouse models of endometriosis for pathological and immunological research. Front Immunol 2022; 13:986202. [PMID: 36466829 PMCID: PMC9716019 DOI: 10.3389/fimmu.2022.986202] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 10/24/2022] [Indexed: 08/30/2023] Open
Abstract
Endometriosis is an estrogen-dependent gynecological disease with chronic pelvic inflammation. In order to study the pathophysiology of endometriosis and examine the therapeutic effects of new pharmaceuticals for endometriosis treatment, different animal models had been developed in the last two decades, especially mouse models. However, no study evaluated the effects of various modeling approaches on pathology and immunology in endometriosis. This study aimed to compare endometriotic lesion development and immune profiles under different methods of establishing endometriosis models in mice, including estrus synchronization (ovariectomy with estrogen supplement versus male urine-soaked transfer bedding), endometrium preparations (whole uterus including endometrium and myometrium fragments versus solely endometrium fragments), and surgical transplantation (subcutaneous transplantation versus intraperitoneal injection). Our results showed that lesion growth under estrus synchronization by ovariectomy with estrogen supplement had a higher success rate and more proliferative endometrium, apart from higher body weight gain. Immune responses in peripheral blood were similar in the whole uterus and solely endometrium fragments and in intraperitoneal injection and subcutaneous transplantation, but a more innate immune response in the peritoneal microenvironment was found in solely endometrium fragments and intraperitoneal injection than counterparts. In conclusion, different endometriosis modeling methods result in different pathological and immunological features. Ovariectomy with estrogen supplement, solely endometrium fragments, and intraperitoneal injection are more suitable for both pathological and immunological studies of endometriosis in mice, which are important for mechanistic studies and immunotherapy development.
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Affiliation(s)
- Ying He
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Gynecological Oncology, Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Bo Liang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Sze Wan Hung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Ruizhe Zhang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Hui Xu
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jacqueline Pui Wah Chung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Chi Chiu Wang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Chinese University of Hong Kong, Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
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21
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Rodrigues J, Wang YF, Singh A, Hendriks M, Dharmalingam G, Cohen-Solal M, Kusumbe AP, Ramasamy SK. Oestrogen enforces the integrity of blood vessels in the bone during pregnancy and menopause. NATURE CARDIOVASCULAR RESEARCH 2022; 1:918-932. [PMID: 36531334 PMCID: PMC7613952 DOI: 10.1038/s44161-022-00139-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 09/02/2022] [Indexed: 04/27/2025]
Abstract
The mammalian skeletal system shows sex differences in structure, functions, ageing and disease incidences. The role of blood vessels in physiological, regenerative and pathological bone functions indicates the requisite to understanding their sex specificity. Here, we find oestrogen regulates blood vessel physiology during pregnancy and menopause through oestrogen receptor alpha (ERα) and G-protein coupled oestrogen receptor-1 (Gper1) but not ERβ-dependent signalling in mice. Oestrogen regulates BECs' lipid use and promotes lipolysis of adipocytes and FA uptake from the microenvironment. Low oestrogen conditions skew endothelial FA metabolism to accumulate lipid peroxides (LPO), leading to vascular ageing. High ferrous ion levels in female BECs intensify LPO accumulation and accelerate the ageing process. Importantly, inhibiting LPO generation using liproxstatin-1 in aged mice significantly improved bone heath. Thus, our findings illustrate oestrogen's effects on BECs and suggest LPO targeting could be an efficient strategy to manage blood and bone health in females.
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Affiliation(s)
- Julia Rodrigues
- Institute of Clinical Sciences, Imperial College London, London, UK
- MRC London Institute of Medical Sciences, Imperial College London, London, UK
| | - Yi-Fang Wang
- Bioinformatics and Computing Facility, MRC London Institute of Medical Sciences, Imperial College London, London, UK
| | - Amit Singh
- Tissue and Tumor Microenvironments Group, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
- Heidelberg University Biochemistry Center, University of Heidelberg, Heidelberg, Germany
| | - Michelle Hendriks
- Institute of Clinical Sciences, Imperial College London, London, UK
- MRC London Institute of Medical Sciences, Imperial College London, London, UK
| | - Gopuraja Dharmalingam
- Bioinformatics and Computing Facility, MRC London Institute of Medical Sciences, Imperial College London, London, UK
| | - Martine Cohen-Solal
- Bioscar Inserm U1132 and Université de Paris, Hospital Lariboisiere, Paris, France
| | - Anjali P Kusumbe
- Tissue and Tumor Microenvironments Group, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
| | - Saravana K Ramasamy
- Institute of Clinical Sciences, Imperial College London, London, UK.
- MRC London Institute of Medical Sciences, Imperial College London, London, UK.
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22
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Zhu J, Zhou W, Xie Z, Li W, Zhuo K. Impact of Sex and Menopausal Status on the Association Between Epicardial Adipose Tissue and Diastolic Function in Patients with Type 2 Diabetes Mellitus. Acad Radiol 2022; 30:823-832. [PMID: 36114077 DOI: 10.1016/j.acra.2022.08.017] [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: 06/20/2022] [Revised: 08/07/2022] [Accepted: 08/12/2022] [Indexed: 11/01/2022]
Abstract
OBJECTIVE To evaluate the impact of sex and menopausal status on the association between the epicardial adipose tissue (EAT) volume and diastolic function in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS A total of 542 consecutive patients with T2DM were retrospectively included in this study. All patients underwent cardiac computed tomographic as well as echocardiography. To assess the independent association of EAT and diastolic function parameters, we performed a multivariate linear regression analysis. RESULTS The median EAT volume was 113.11 cm3 (interquartile range (IQR): 88.38, 148.03), and EAT volume was higher in men than in women (p < 0.05). We also discovered that EAT volume was significantly associated with diastolic function in both sexes after adjusting for risk factors (p < 0.05). Concerning menopausal status, EAT volume was higher in postmenopausal women than premenopausal women and was independently associated with the diastolic function only in postmenopausal women. CONCLUSION In patients with T2DM, EAT is independently associated with diastolic function in the male population and a portion of the female population. In contrast to premenopausal women, EAT volume is only significantly correlated with diastolic function in postmenopausal women.
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Affiliation(s)
- Jing Zhu
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Wei Zhou
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Zhen Xie
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Wenjia Li
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Kaimin Zhuo
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
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23
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Wu M, Guo Y, Wei S, Xue L, Tang W, Chen D, Xiong J, Huang Y, Fu F, Wu C, Chen Y, Zhou S, Zhang J, Li Y, Wang W, Dai J, Wang S. Biomaterials and advanced technologies for the evaluation and treatment of ovarian aging. J Nanobiotechnology 2022; 20:374. [PMID: 35953871 PMCID: PMC9367160 DOI: 10.1186/s12951-022-01566-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 07/17/2022] [Indexed: 12/26/2022] Open
Abstract
Ovarian aging is characterized by a progressive decline in ovarian function. With the increase in life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Over the years, various strategies have been developed to preserve fertility in women, while there are currently no clinical treatments to delay ovarian aging. Recently, advances in biomaterials and technologies, such as three-dimensional (3D) printing and microfluidics for the encapsulation of follicles and nanoparticles as delivery systems for drugs, have shown potential to be translational strategies for ovarian aging. This review introduces the research progress on the mechanisms underlying ovarian aging, and summarizes the current state of biomaterials in the evaluation and treatment of ovarian aging, including safety, potential applications, future directions and difficulties in translation.
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Affiliation(s)
- Meng Wu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Yican Guo
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Simin Wei
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Liru Xue
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Weicheng Tang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Dan Chen
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Jiaqiang Xiong
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Yibao Huang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Fangfang Fu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Chuqing Wu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Ying Chen
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Su Zhou
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Jinjin Zhang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Yan Li
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Wenwen Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. .,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China. .,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China.
| | - Jun Dai
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China.,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China
| | - Shixuan Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. .,National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, 430030, Hubei, China. .,Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, 430030, Hubei, China.
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24
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Wu Q, Zhang F, Li R, Li W, Gou D, Wang L. Identification of the Best Anthropometric Index for Predicting the 10-Year Cardiovascular Disease in Southwest China: A Large Single-Center, Cross-Sectional Study. High Blood Press Cardiovasc Prev 2022; 29:417-428. [PMID: 35776364 DOI: 10.1007/s40292-022-00528-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 06/02/2022] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION This population-based cross-sectional study aimed to identify the best predictor of the 10-year cardiovascular (CV) high risk among old and new anthropometric indices. METHODS We investigated 76,915 adults older than 18 years of age living in southwest China. Ten obesity indices were calculated. The 10-year cardiovascular disease (CVD) risk was estimated using the Framingham risk score. Receiver operating characteristic curve analysis was performed to assess the ability of the anthropometric index to predict the 10-year high risk of CVD events. RESULTS The waist-to-hip ratio (WHR) had the highest area under the curve (AUC) value (0.711; sensitivity: 62.22%, specificity: 42.73%) in men, while the body fat index (BAI) had the lowest AUC value (0.624, sensitivity: 49.07%, specificity: 54.84%). The waist-to-height ratio (WHtR) and the body roundness index (BRI) showed the highest AUC value (0.751, sensitivity: 39.24%, 39.83%, specificity: 75.68%, 68.59%) in women, while the BAI showed the lowest AUC value (0.671, sensitivity: 53.15%, specificity: 57.14%). CONCLUSIONS The WHR was the best anthropometric measure for assessing the 10-year high risk of CVD in men, while the WHtR and BRI were the best measures for women. In men, the WHR should be < 0.88, and in women, the WHtR should be < 0.502 or the BRI should be < 3.41.
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Affiliation(s)
- Qinqin Wu
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Fan Zhang
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Ruicen Li
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenyu Li
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Gou
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lin Wang
- Department of Cardiology, West China Hospital, Sichuan University, No.37 Guoxue Road, Chengdu, 610041, Sichuan, China.
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25
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Khadilkar V, Oza C, Khadilkar A. Relationship between height age, bone age and chronological age in normal children in the context of nutritional and pubertal status. J Pediatr Endocrinol Metab 2022; 35:767-775. [PMID: 35487031 DOI: 10.1515/jpem-2021-0698] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 04/04/2022] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Bone age (BA) is a quantitative determination of skeletal maturation. The role of puberty in variations in BA is poorly understood as hypothalamic-pituitary-gonadal (HPG) axis maturation and skeletal maturation are regulated in parallel but independently by multiple different factors. In countries like India where there is rapid nutrition transition and increase in prevalence of obesity, their impact on height and BA is not well understood. OBJECTIVES To study if in 2-17 year old healthy children, the difference between chronological age (CA), height age (HA) and BA is less than 1 year on either side of the chronological age and to assess relationship of BA with height, weight and BMI with special reference to gender and puberty. METHODS This cross-sectional study included 804 preschool/school-going Indian children. Anthropometric measurements and pubertal assessments were performed using standard protocols and were converted to age and sex standardized z-scores using Indian references while BA was estimated by Tanner-Whitehouse (TW3) method. p<0.05 was considered statistically significant. RESULTS The mean age and gender standardized z-scores for height, weight, body mass index (BMI) and BA were -0.3 ± 0.7, -0.7 ± 0.8, -0.1 ± 1.0, and -0.2 ± 0.9 respectively. HA was more delayed in girls while BA was more delayed in boys. The mean BA z-score increased with increasing BMI. After the onset of puberty, there was higher increment in BA in girls and HA in boys (p<0.05). CONCLUSIONS HA, BA and CA were tightly correlated in healthy Indian children with a significant role of nutritional status and puberty in causing variation in the same.
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Affiliation(s)
- Vaman Khadilkar
- Senior Pediatric Endocrinologist, Jehangir Hospital, Bombay Hospital, Pune, India.,Department of Health Sciences, Savitribai Phule Pune University, Pune, Maharashtra, India
| | - Chirantap Oza
- Hirabai Cowasji Jehangir Medical Research Institute, Pune, India
| | - Anuradha Khadilkar
- Department of Health Sciences, Savitribai Phule Pune University, Pune, Maharashtra, India.,Hirabai Cowasji Jehangir Medical Research Institute, Pune, India
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26
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MiRNA-320a-5p contributes to the homeostasis of osteogenesis and adipogenesis in bone marrow mesenchymal stem cell. Regen Ther 2022; 20:32-40. [PMID: 35402661 PMCID: PMC8968203 DOI: 10.1016/j.reth.2022.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 01/19/2022] [Accepted: 03/02/2022] [Indexed: 11/23/2022] Open
Abstract
Objective A number of miRNAs and their targets were dragged in the differentiation of bone marrow mesenchymal stem cells (BMSCs). We aimed to elaborate the underlying molecular mechanisms of miRNA-320a in the osteoblast and adipocyte differentiation. Methods Trauma-induced osteonecrosis of the femoral head (TIONFH) and normal control samples (n = 10 for each group) were collected, followed by miRNA chip analysis to identify the differentially expressed miRNAs. H&E staining was used to observe the pathological development of TIONFH. Lentiviral vector was used for overexpression and inhibition of miRNA-320a in vitro. Quantitative real-time PCR (qPCR), Western blotting and immunohistochemistry staining were employed to determine the expression of interested genes at mRNA or protein level. Luciferase report assay was employed to determine the binding of miRNA-320a and RUNX2. Alkaline phosphatase (ALP) and Alizarin red staining were performed to observe the osteogenesis and Oil red O staining were conducted to visualize the adipogenesis. Results Expression of miRNA-320a was up-regulated while RUNX2 expression was down-regulated in TIONFH than Normal control. Luciferase report assay confirmed that miRNA-320a directly targeted to the 3′UTR of RUNX2. miRNA-320a overexpression significantly declined the expressions of osteogenesis-related markers: RUNX2, OSTERIX, Collagen I, Osteocalcin and Osteopontin. ALP and Alizarin red staining confirmed the inhibition function of miRNA-320a in osteogenesis of BMSCs. miRNA-320a inhibition significantly decreased the expression of adipogenesis-related markers: AP2, C/EBPα, FABP4 and PPARγ. Oil Red O staining confirmed the miRNA-320a inhibition reduced adipogenesis of BMSCs. Conclusions miRNA-320a inhibits osteoblast differentiation via targeting RUNX2 and promotes adipocyte differentiation of BMSCs.
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27
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Steiner BM, Berry DC. The Regulation of Adipose Tissue Health by Estrogens. Front Endocrinol (Lausanne) 2022; 13:889923. [PMID: 35721736 PMCID: PMC9204494 DOI: 10.3389/fendo.2022.889923] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/25/2022] [Indexed: 12/14/2022] Open
Abstract
Obesity and its' associated metabolic diseases such as type 2 diabetes and cardiometabolic disorders are significant health problems confronting many countries. A major driver for developing obesity and metabolic dysfunction is the uncontrolled expansion of white adipose tissue (WAT). Specifically, the pathophysiological expansion of visceral WAT is often associated with metabolic dysfunction due to changes in adipokine secretion profiles, reduced vascularization, increased fibrosis, and enrichment of pro-inflammatory immune cells. A critical determinate of body fat distribution and WAT health is the sex steroid estrogen. The bioavailability of estrogen appears to favor metabolically healthy subcutaneous fat over visceral fat growth while protecting against changes in metabolic dysfunction. Our review will focus on the role of estrogen on body fat partitioning, WAT homeostasis, adipogenesis, adipocyte progenitor cell (APC) function, and thermogenesis to control WAT health and systemic metabolism.
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Affiliation(s)
| | - Daniel C. Berry
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States
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Non-alcoholic fatty liver disease: a multi-system disease influenced by ageing and sex, and affected by adipose tissue and intestinal function. Proc Nutr Soc 2022; 81:146-161. [DOI: 10.1017/s0029665121003815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
In recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is first to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including CVD, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD – a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases.
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Heindel JJ, Howard S, Agay-Shay K, Arrebola JP, Audouze K, Babin PJ, Barouki R, Bansal A, Blanc E, Cave MC, Chatterjee S, Chevalier N, Choudhury M, Collier D, Connolly L, Coumoul X, Garruti G, Gilbertson M, Hoepner LA, Holloway AC, Howell G, Kassotis CD, Kay MK, Kim MJ, Lagadic-Gossmann D, Langouet S, Legrand A, Li Z, Le Mentec H, Lind L, Monica Lind P, Lustig RH, Martin-Chouly C, Munic Kos V, Podechard N, Roepke TA, Sargis RM, Starling A, Tomlinson CR, Touma C, Vondracek J, Vom Saal F, Blumberg B. Obesity II: Establishing causal links between chemical exposures and obesity. Biochem Pharmacol 2022; 199:115015. [PMID: 35395240 PMCID: PMC9124454 DOI: 10.1016/j.bcp.2022.115015] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/12/2022] [Accepted: 03/15/2022] [Indexed: 02/06/2023]
Abstract
Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
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Affiliation(s)
- Jerrold J Heindel
- Healthy Environment and Endocrine Disruptor Strategies, Commonweal, Bolinas, CA 92924, USA.
| | - Sarah Howard
- Healthy Environment and Endocrine Disruptor Strategies, Commonweal, Bolinas, CA 92924, USA
| | - Keren Agay-Shay
- Health and Environment Research (HER) Lab, The Azrieli Faculty of Medicine, Bar Ilan University, Israel
| | - Juan P Arrebola
- Department of Preventive Medicine and Public Health University of Granada, Granada, Spain
| | - Karine Audouze
- Department of Systems Biology and Bioinformatics, University of Paris, INSERM, T3S, Paris France
| | - Patrick J Babin
- Department of Life and Health Sciences, University of Bordeaux, INSERM, Pessac France
| | - Robert Barouki
- Department of Biochemistry, University of Paris, INSERM, T3S, 75006 Paris, France
| | - Amita Bansal
- College of Health & Medicine, Australian National University, Canberra, Australia
| | - Etienne Blanc
- Department of Biochemistry, University of Paris, INSERM, T3S, 75006 Paris, France
| | - Matthew C Cave
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY 40402, USA
| | - Saurabh Chatterjee
- Environmental Health and Disease Laboratory, University of South Carolina, Columbia, SC 29208, USA
| | - Nicolas Chevalier
- Obstetrics and Gynecology, University of Cote d'Azur, Cote d'Azur, France
| | - Mahua Choudhury
- College of Pharmacy, Texas A&M University, College Station, TX 77843, USA
| | - David Collier
- Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
| | - Lisa Connolly
- The Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, UK
| | - Xavier Coumoul
- Department of Biochemistry, University of Paris, INSERM, T3S, 75006 Paris, France
| | - Gabriella Garruti
- Department of Endocrinology, University of Bari "Aldo Moro," Bari, Italy
| | - Michael Gilbertson
- Occupational and Environmental Health Research Group, University of Stirling, Stirling, Scotland
| | - Lori A Hoepner
- Department of Environmental and Occupational Health Sciences, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Alison C Holloway
- McMaster University, Department of Obstetrics and Gynecology, Hamilton, Ontario, CA, USA
| | - George Howell
- Center for Environmental Health Sciences, Mississippi State University, Mississippi State, MS 39762, USA
| | - Christopher D Kassotis
- Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, USA
| | - Mathew K Kay
- College of Pharmacy, Texas A&M University, College Station, TX 77843, USA
| | - Min Ji Kim
- Sorbonne Paris Nord University, Bobigny, INSERM U1124 (T3S), Paris, France
| | | | - Sophie Langouet
- Univ Rennes, INSERM EHESP, IRSET UMR_5S 1085, 35000 Rennes, France
| | - Antoine Legrand
- Sorbonne Paris Nord University, Bobigny, INSERM U1124 (T3S), Paris, France
| | - Zhuorui Li
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
| | - Helene Le Mentec
- Sorbonne Paris Nord University, Bobigny, INSERM U1124 (T3S), Paris, France
| | - Lars Lind
- Clinical Epidemiology, Department of Medical Sciences, Uppsala University Hospital, Uppsala University, Uppsala, Sweden
| | - P Monica Lind
- Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University Hospital, Uppsala University, Uppsala, Sweden
| | - Robert H Lustig
- Division of Endocrinology, Department of Pediatrics, University of California San Francisco, CA 94143, USA
| | | | - Vesna Munic Kos
- Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden
| | - Normand Podechard
- Sorbonne Paris Nord University, Bobigny, INSERM U1124 (T3S), Paris, France
| | - Troy A Roepke
- Department of Animal Science, School of Environmental and Biological Science, Rutgers University, New Brunswick, NJ 08901, USA
| | - Robert M Sargis
- Division of Endocrinology, Diabetes and Metabolism, The University of Illinois at Chicago, Chicago, Il 60612, USA
| | - Anne Starling
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Craig R Tomlinson
- Norris Cotton Cancer Center, Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
| | - Charbel Touma
- Sorbonne Paris Nord University, Bobigny, INSERM U1124 (T3S), Paris, France
| | - Jan Vondracek
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic
| | - Frederick Vom Saal
- Division of Biological Sciences, The University of Missouri, Columbia, MO 65211, USA
| | - Bruce Blumberg
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Plante I, Winn LM, Vaillancourt C, Grigorova P, Parent L. Killing two birds with one stone: Pregnancy is a sensitive window for endocrine effects on both the mother and the fetus. ENVIRONMENTAL RESEARCH 2022; 205:112435. [PMID: 34843719 DOI: 10.1016/j.envres.2021.112435] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 06/13/2023]
Abstract
Pregnancy is a complex process requiring tremendous physiological changes in the mother in order to fulfill the needs of the growing fetus, and to give birth, expel the placenta and nurse the newborn. These physiological modifications are accompanied with psychological changes, as well as with variations in habits and behaviors. As a result, this period of life is considered as a sensitive window as impaired functional and physiological changes in the mother can have short- and long-term impacts on her health. In addition, dysregulation of the placenta and of mechanisms governing placentation have been linked to chronic diseases later-on in life for the fetus, in a concept known as the Developmental Origin of Health and Diseases (DOHaD). This concept stipulates that any change in the environment during the pre-conception and perinatal (in utero life and neonatal) period to puberty, can be "imprinted" in the organism, thereby impacting the health and risk of chronic diseases later in life. Pregnancy is a succession of events that is regulated, in large part, by hormones and growth factors. Therefore, small changes in hormonal balance can have important effects on both the mother and the developing fetus. An increasing number of studies demonstrate that exposure to endocrine disrupting compounds (EDCs) affect both the mother and the fetus giving rise to growing concerns surrounding these exposures. This review will give an overview of changes that happen during pregnancy with respect to the mother, the placenta, and the fetus, and of the current literature regarding the effects of EDCs during this specific sensitive window of exposure.
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Affiliation(s)
- Isabelle Plante
- INRS-Centre Armand-Frappier Santé Biotechnologie, Laval, QC, Canada.
| | - Louise M Winn
- Queen's University, School of Environmental Studies, Department of Biomedical and Molecular Sciences, Kingston, ON, Canada
| | | | - Petya Grigorova
- Département Science et Technologie, Université TELUQ, Montreal, QC, Canada
| | - Lise Parent
- Département Science et Technologie, Université TELUQ, Montreal, QC, Canada
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Lustig RH, Collier D, Kassotis C, Roepke TA, Ji Kim M, Blanc E, Barouki R, Bansal A, Cave MC, Chatterjee S, Choudhury M, Gilbertson M, Lagadic-Gossmann D, Howard S, Lind L, Tomlinson CR, Vondracek J, Heindel JJ. Obesity I: Overview and molecular and biochemical mechanisms. Biochem Pharmacol 2022; 199:115012. [PMID: 35393120 PMCID: PMC9050949 DOI: 10.1016/j.bcp.2022.115012] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 03/12/2022] [Accepted: 03/15/2022] [Indexed: 02/06/2023]
Abstract
Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the "obesogen hypothesis" (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.
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Affiliation(s)
- Robert H Lustig
- Division of Endocrinology, Department of Pediatrics, University of California, San Francisco, CA 94143, United States
| | - David Collier
- Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States
| | - Christopher Kassotis
- Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, United States
| | - Troy A Roepke
- School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, United States
| | - Min Ji Kim
- Department of Biochemistry and Toxicology, University of Paris, INSERM U1224 (T3S), 75006 Paris, France
| | - Etienne Blanc
- Department of Biochemistry and Toxicology, University of Paris, INSERM U1224 (T3S), 75006 Paris, France
| | - Robert Barouki
- Department of Biochemistry and Toxicology, University of Paris, INSERM U1224 (T3S), 75006 Paris, France
| | - Amita Bansal
- College of Health & Medicine, Australian National University, Canberra, Australia
| | - Matthew C Cave
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY 40402, United States
| | - Saurabh Chatterjee
- Environmental Health and Disease Laboratory, University of South Carolina, Columbia, SC 29208, United States
| | - Mahua Choudhury
- College of Pharmacy, Texas A&M University, College Station, TX 77843, United States
| | - Michael Gilbertson
- Occupational and Environmental Health Research Group, University of Stirling, Stirling, Scotland, United Kingdom
| | - Dominique Lagadic-Gossmann
- Research Institute for Environmental and Occupational Health, University of Rennes, INSERM, EHESP, Rennes, France
| | - Sarah Howard
- Healthy Environment and Endocrine Disruptor Strategies, Commonweal, Bolinas, CA 92924, United States
| | - Lars Lind
- Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
| | - Craig R Tomlinson
- Norris Cotton Cancer Center, Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States
| | - Jan Vondracek
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic
| | - Jerrold J Heindel
- Healthy Environment and Endocrine Disruptor Strategies, Commonweal, Bolinas, CA 92924, United States.
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32
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Gustafsson KL, Movérare-Skrtic S, Farman HH, Engdahl C, Henning P, Nilsson KH, Scheffler JM, Sehic E, Islander U, Levin E, Ohlsson C, Lagerquist MK. A tissue-specific role of membrane-initiated ERα signaling for the effects of SERMs. J Endocrinol 2022; 253:75-84. [PMID: 35256537 PMCID: PMC9066589 DOI: 10.1530/joe-21-0398] [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: 03/01/2022] [Accepted: 03/07/2022] [Indexed: 11/25/2022]
Abstract
Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To determine if membrane-initiated ERα (mERα) signaling affects SERM action in a tissue-specific manner, C451A mice, lacking mERα signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradiol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mERα-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mERα-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were absent in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in the skeleton are mERα-dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrating mERα-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mERα signaling. In conclusion, mERα signaling can modulate SERM responses in a tissue-specific manner. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.
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Affiliation(s)
- Karin L Gustafsson
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Correspondence should be addressed to K L Gustafsson:
| | - Sofia Movérare-Skrtic
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Helen H Farman
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Cecilia Engdahl
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Petra Henning
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Karin H Nilsson
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Julia M Scheffler
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Edina Sehic
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Ulrika Islander
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Ellis Levin
- Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, California, USA
- Department of Veterans Affairs Medical Center, Long Beach, Long Beach, California, USA
| | - Claes Ohlsson
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Marie K Lagerquist
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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Chen X, Ma Z, Chen P, Song X, Li W, Yu X, Xie J. Case Report: A New Peroxisome Proliferator-Activated Receptor Gamma Mutation Causes Familial Partial Lipodystrophy Type 3 in a Chinese Patient. Front Endocrinol (Lausanne) 2022; 13:830708. [PMID: 35422762 PMCID: PMC9001891 DOI: 10.3389/fendo.2022.830708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/23/2022] [Indexed: 11/18/2022] Open
Abstract
PURPOSE Familial partial lipodystrophy type 3 (FPLD3) is an autosomal dominant disease. Patients typically present with loss of adipose tissue and metabolic complications. Here, we reported a Chinese FPLD3 patient with a novel PPARG gene mutation. METHODS A 16-year-old female patient and her relatives were assessed by detailed clinical and biochemical examinations. Sequencing was performed by using the extracted DNA. Moreover, we identified FPLD3 patients from previous studies, and according to the protein region affected by the gene mutation. We divided the patients into the DNA-binding domain (DBD) group or the ligand-binding domain (LBD) group, and compared the clinical features between the two groups. RESULTS We identified a novel gene mutation affecting the LBD of PPARγ c.929T > C (p.F310S). This mutation leads to the substitution of a phenylalanine by a serine. In our case, subcutaneous fat was significantly diminished in her face, hips and limbs. The patient was also presented with insulin resistance, diabetes mellitus, hypertriglyceridemia, fatty liver, liver dysfunction, albuminuria and diabetic peripheral neuropathy. After literature review, a total of 58 FPLD3 patients were identified and we found no difference in clinical features between the DBD group and LBD group (all P > 0.05). CONCLUSIONS A Chinese FPLD3 patient with a novel PPARG gene mutation is described. Our case emphasized the importance of physical examination and genetic testing in young patients with severe metabolic syndromes.
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Affiliation(s)
- Xi Chen
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Internal Medicine, Branch of National Clinical Research Center for Metabolic Disease, Wuhan, China
| | - Zhiqiang Ma
- Division of Cardiology, Departments of Internal Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Peng Chen
- Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Internal Medicine, Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan, China
| | - Xiuli Song
- Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Internal Medicine, Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan, China
| | - Weihua Li
- Division of Cardiology, Departments of Internal Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuefeng Yu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Internal Medicine, Branch of National Clinical Research Center for Metabolic Disease, Wuhan, China
| | - Junhui Xie
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Internal Medicine, Branch of National Clinical Research Center for Metabolic Disease, Wuhan, China
- *Correspondence: Junhui Xie,
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Marlatt KL, Pitynski-Miller DR, Gavin KM, Moreau KL, Melanson EL, Santoro N, Kohrt WM. Body composition and cardiometabolic health across the menopause transition. Obesity (Silver Spring) 2022; 30:14-27. [PMID: 34932890 PMCID: PMC8972960 DOI: 10.1002/oby.23289] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/15/2021] [Accepted: 08/09/2021] [Indexed: 12/23/2022]
Abstract
Every year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause-known as the menopause transition (or perimenopause)-changes in hormones and body composition increase a woman's overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition. We also discuss the benefits of lifestyle interventions in women in the earlier stages of menopause before these detrimental changes occur. Finally, we discuss how to include perimenopausal women in research studies so that women across the life-span are adequately represented.
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Affiliation(s)
- Kara L. Marlatt
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
| | - Dori R. Pitynski-Miller
- Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Eastern Colorado VA Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado, USA
| | - Kathleen M. Gavin
- Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Eastern Colorado VA Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado, USA
| | - Kerrie L. Moreau
- Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Eastern Colorado VA Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado, USA
| | - Edward L. Melanson
- Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Eastern Colorado VA Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado, USA
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Nanette Santoro
- Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Wendy M. Kohrt
- Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Eastern Colorado VA Health Care System, Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado, USA
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35
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Siriarchavatana P, Kruger MC, Miller MR, Tian H(S, Wolber FM. The Influence of Obesity, Ovariectomy, and Greenshell Mussel Supplementation on Bone Mineral Density in Rats. JBMR Plus 2022; 6:e10571. [PMID: 35079679 PMCID: PMC8771000 DOI: 10.1002/jbm4.10571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 10/05/2021] [Accepted: 10/19/2021] [Indexed: 11/18/2022] Open
Abstract
Obesity is considered to impair long-term health by disturbing multiple physiological functions. However, it remains a controversial issue as to whether obesity has beneficial or detrimental effects on bone health in postmenopausal women. The aims of this study were to investigate the relationships between obesity and bone mineral density (BMD) under conditions of ovarian hormone deficiency in an animal model and to evaluate the potential health benefits of Greenshell mussel (GSM) on bone health. A total of 144 adult female Sprague-Dawley rats were fed from age 12 weeks on one of four diets (normal [ND]; ND + GSM; high fat/high sugar [HF/HS]; HF/HS + GSM; n = 36 per diet). At age 20 weeks, after a dual-energy X-ray absorptiometry (DXA) scan, 12 of the rats on each diet underwent ovariectomy (OVX) and the remaining rats were left intact. Twelve of the intact rats in each diet group were culled at age 26 weeks (short-term cohort). The remaining rats were culled at age 48 weeks (long-term cohort). Rats were DXA scanned before cull, then various fat pads were dissected. The results revealed that HF/HS rats and OVX rats dramatically increased body weight and fat deposition in correlation with leptin. In the long-term cohort, vertebral spine BMD rapidly declined after OVX. At termination, the OVX rats had decreased plasma bone turnover markers of CTX-1 and TRAP when compared with sham rats. Significantly higher BMD was found in OVX rats fed the HF/HS diet compared with ND, but this difference was not recapitulated in intact rats. BMD of right femur was significantly increased 5% to 10% by GSM in the short-term cohort. The data demonstrated that obesity can be beneficial by increasing BMD in OVX rats, and this may extrapolate to postmenopausal women as adipocyte-produced estrogen may slightly compensate for the reduction in ovarian hormones. Finally, the data showed that GSM may be beneficial to bone health by increasing BMD accrual. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Parkpoom Siriarchavatana
- School of Food and Advanced TechnologyMassey UniversityPalmerston NorthNew Zealand
- Department of Pharmacology, Faculty of Veterinary ScienceChulalongkorn UniversityBangkokThailand
| | - Marlena C Kruger
- School of Health SciencesMassey UniversityPalmerston NorthNew Zealand
- Riddet Centre of Research ExcellenceMassey UniversityPalmerston NorthNew Zealand
| | | | | | - Frances M Wolber
- School of Food and Advanced TechnologyMassey UniversityPalmerston NorthNew Zealand
- Centre for Metabolic Health ResearchMassey UniversityPalmerston NorthNew Zealand
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Bjune JI, Strømland PP, Jersin RÅ, Mellgren G, Dankel SN. Metabolic and Epigenetic Regulation by Estrogen in Adipocytes. Front Endocrinol (Lausanne) 2022; 13:828780. [PMID: 35273571 PMCID: PMC8901598 DOI: 10.3389/fendo.2022.828780] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.
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Affiliation(s)
- Jan-Inge Bjune
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Pouda Panahandeh Strømland
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | - Regine Åsen Jersin
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Gunnar Mellgren
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Simon Nitter Dankel
- Hormone Laboratory, Department of Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
- *Correspondence: Simon Nitter Dankel,
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Autologous mesenchymal stem cells in the treatment of spinal aneurysmal bone cyst. Pathol Res Pract 2021; 229:153722. [PMID: 34952421 DOI: 10.1016/j.prp.2021.153722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 11/20/2022]
Abstract
PURPOSE We retrospectively analyzed a cohort of patients treated at our Centre with bone marrow concentrated (BMC) injection for aneurysmal bone cyst (ABC) of the spine, in order to propose this treatment as a valid alternative for the management of ABCs. METHODS Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 15.5 years. The mean follow up was 37.4 months (range 12-60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. RESULTS Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48 ± 2.36 HU to 161.71 ± 23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up CONCLUSIONS: Results of this paper reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE treatment is contraindicated or ineffective.
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Boudalia S, Bousbia A, Boumaaza B, Oudir M, Canivenc Lavier MC. Relationship between endocrine disruptors and obesity with a focus on bisphenol A: a narrative review. BIOIMPACTS 2021; 11:289-300. [PMID: 34631491 PMCID: PMC8494257 DOI: 10.34172/bi.2021.33] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 04/25/2020] [Accepted: 05/10/2020] [Indexed: 11/09/2022]
Abstract
Introduction: Scientific data suggest that early exposure to endocrine-disrupting chemicals (EDCs) affect -repro, -neuro, -metabolic systems, to which are added other notions such as mixtures, window and duration of exposure, trans-generational effects, and epigenetic mechanisms. Methods: In the present narrative review, we studied the relationship between exposure to EDCs with the appearance and development of obesity. Results: Exposure to EDCs like Bisphenol A during the early stages of development has been shown to lead to weight gain and obesity. EDCs can interfere with endocrine signaling, affect adipocytes differentiation and endocrine function and disrupt metabolic processes, especially if exposure occurs at very low doses, in the mixture, during early development stages for several generations. Conclusion: Exposure to EDCs is positively associated with obesity development. Moreover, the use of integrative approaches which mimicking environmental conditions are necessary and recommended to evaluate EDCs' effects in future studies.
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Affiliation(s)
- Sofiane Boudalia
- Faculté des Sciences de la Nature et de la Vie et Sciences de la Terre et de l'Univers, Université 8 Mai 1945 Guelma BP 4010 Guelma 24000, Algérie.,Laboratoire de Biologie, Eau et Environnement, Université 8 Mai 1945 Guelma BP 4010 Guelma 24000, Algérie
| | - Aissam Bousbia
- Faculté des Sciences de la Nature et de la Vie et Sciences de la Terre et de l'Univers, Université 8 Mai 1945 Guelma BP 4010 Guelma 24000, Algérie.,Laboratoire de Biologie, Eau et Environnement, Université 8 Mai 1945 Guelma BP 4010 Guelma 24000, Algérie
| | - Boualem Boumaaza
- Laboratoire de Biologie, Eau et Environnement, Université 8 Mai 1945 Guelma BP 4010 Guelma 24000, Algérie.,Département des Sciences Agronomiques, Faculté des Sciences de la Nature et de la Vie, Université Ibn Khaldoun, Tiaret 14000, Algérie
| | - Malha Oudir
- Laboratoire de Génie Chimique, Département de Génie des Procédés, Faculté de Technologie, Université Saâd Dahlab, USDB. BP 270, Route de Soumâa, 09000 Blida, Algérie
| | - Marie Chantal Canivenc Lavier
- Centre des Sciences du Goût et de l'Alimentation, INRA, CNRS, Université de Bourgogne - Franche-Comté, Dijon, 21000, France
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Minicozzi MR, Axlid EG, von Hippel FA, Espinoza J, Funke A, Phillips QP, Buck CL. Perchlorate exposure does not induce obesity or non-alcoholic fatty liver disease in zebrafish. PLoS One 2021; 16:e0254500. [PMID: 34347796 PMCID: PMC8336815 DOI: 10.1371/journal.pone.0254500] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 06/28/2021] [Indexed: 12/31/2022] Open
Abstract
Perchlorate is a water-soluble contaminant found throughout the United States and many other countries. Perchlorate competitively inhibits iodide uptake at the sodium/iodide symporter, reducing thyroid hormone synthesis, which can lead to hypothyroidism and metabolic syndromes. Chronic perchlorate exposure induces hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) in developing threespine stickleback (Gasterosteus aculeatus). We hypothesized that perchlorate would also induce zebrafish (Danio rerio) to develop phenotypes consistent with NAFLD and to accumulate lipids throughout the body. We exposed zebrafish embryos to four concentrations of perchlorate treated water (10μg/L, 10mg/L, 30mg/L, and 100mg/L) and a control (0mg/L) over the course of 133 days. Adult zebrafish were euthanized, sectioned, H&E and Oil Red-O stained, and analyzed for liver morphology and whole body lipid accumulation. In a representative section of the liver, we counted the number of lipid droplets and measured the area of each droplet and the total lipid area. For whole body analysis, we calculated the ratio of lipid area to body area within a section. We found that zebrafish exposed to perchlorate did not differ in any measured liver variables or whole body lipid area when compared to controls. In comparison to stickleback, we see a trend that control stickleback accumulate more lipids in their liver than do control zebrafish. Differences between the species indicate that obesogenic effects due to perchlorate exposure are not uniform across fish species, and likely are mediated by evolutionary differences related to geographic location. For example, high latitude fishes such as stickleback evolved to deposit lipid stores for over-winter survival, which may lead to more pronounced obesogenic effects than seen in tropical fish such as zebrafish.
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Affiliation(s)
- Michael R. Minicozzi
- Department of Biological Sciences, Minnesota State University Mankato, Mankato, MN, United States of America
| | - Erik G. Axlid
- Department of Biological Sciences, Minnesota State University Mankato, Mankato, MN, United States of America
| | - Frank A. von Hippel
- Department of Community, Environment and Policy, The University of Arizona, Tucson, AZ, United States of America
| | - Joseph Espinoza
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United States of America
| | - Aubrey Funke
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United States of America
| | - Quentin P. Phillips
- Department of Biological Sciences, Minnesota State University Mankato, Mankato, MN, United States of America
| | - C. Loren Buck
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United States of America
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Zan G, Li L, Cheng H, Huang L, Huang S, Luo X, Xiao L, Liu C, Zhang H, Mo Z, Yang X. Mediated relationships between multiple metals exposure and fasting blood glucose by reproductive hormones in Chinese men. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 278:116791. [PMID: 33684679 DOI: 10.1016/j.envpol.2021.116791] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 06/12/2023]
Abstract
Previous studies have reported metals exposure contribute to the change of fasting blood glucose (FBG) level. However, the roles of reproductive hormones in their associations have not been fully elucidated. The aim of the study is to investigate the associations of multiple serum metals with reproductive hormones, and to further explore potential roles of reproductive hormones in relationships between metals exposure and FBG level. A total of 1911 Chinese Han men were analyzed by a cross-sectional study. We measured serum levels of 22 metals by inductively coupled plasma mass spectrometer (ICP-MS). FBG, total testosterone (TT), estradiol (E2), follicle stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels were determined. Least absolute shrinkage and selection operator (LASSO) regression models were conducted to select important metals, and restricted cubic spline models were then used to estimate dose-response relationships between selected metals and reproductive hormones. We also conducted mediation analyses to evaluate whether reproductive hormones played mediating roles in the associations between metals and FBG. We found significant inverse dose-dependent trends of copper, tin and zinc with E2; zinc with SHBG; copper and nickel with TT, while significant positive dose-dependent trend of iron with E2, respectively. Moreover, approximately inverted U-shaped associations existed between lead and SHBG, iron and TT. In addition, E2, SHBG and TT were negatively associated with FBG level. In mediation analyses, the association of copper with FBG was mediated by E2 and TT, with a mediation ratio of 10.4% and 22.1%, respectively. Furthermore, E2 and SHBG mediated the relationship of zinc with FBG, with a mediation ratio of 7.8% and 14.5%, respectively. E2 mediated 11.5% of positive relationship between tin with FBG. Our study suggested that the associations of metals exposure with FBG may be mediated by reproductive hormones.
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Affiliation(s)
- Gaohui Zan
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Longman Li
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Hong Cheng
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Lulu Huang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Sifang Huang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Xiaoyu Luo
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Lili Xiao
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Chaoqun Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Haiying Zhang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Xiaobo Yang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, China.
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Amerizadeh A, Asgary S, Vaseghi G, Farajzadegan Z. Effect of Genistein Intake on Some Cardiovascular Risk Factors: An Updated Systematic Review and Meta-analysis. Curr Probl Cardiol 2021; 47:100902. [PMID: 34266697 DOI: 10.1016/j.cpcardiol.2021.100902] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 05/20/2021] [Indexed: 12/14/2022]
Abstract
Genistein, an isoflavone in soybean products has potential cardio-protective effects and is used also as an alternative for estrogen therapy in postmenopausal women. However, results in this regard are inconsistent and also, not all risk factors related to cardiovascular supportive effects have been meta-analyzed. We searched PubMed, Scopus, ISI Web of Science, and Google Scholar from inception up to October 2020. Random-effects meta-analysis was used for data synthesis. The search included studies with information on genistein supplementation and lipid profile [triglycerides (TG), total cholesterol (TC),low-density lipoprotein (LDL-C), and high-density lipoprotein HDL-C)], systolic and diastolic blood pressure (SBP & DBP), body mass index [BMI] and body weight. Pooled results of studies showed that genistein intake significantly reduced TC [95%CI: -0.49(-0.80, -0.18); P=0.002)], LDL-C [95%CI: -0.60(-1.10, -0.10); P=0.018)] and SBP [95%CI: -0.52(-0.90, -0.14); P=0.007)]. DBP, HLD-C, TG, BMI, and body weight showed no meaningful improvement. Subgroup analysis showed that LDL-C and SBP were reduced more effectively in postmenopausal women with metabolic syndrome. Genistein intake more than 6 months showed a greater effect on lowering cholesterol -0.76(-1.27, -0.24), SBP [-0.39(-0.70, -0.08)] and DBP -0.40(-0.81, -0.00) and increasing TG and LDL-C. This meta-analysis provides consistent evidence that genistein intake reduces the CVD risk factors of TC, LDL-C, and SBP significantly.
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Affiliation(s)
- Atefeh Amerizadeh
- Department of Pharmaceutical Sciences, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Sedigheh Asgary
- Department of Pharmaceutical Sciences, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Golnaz Vaseghi
- Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ziba Farajzadegan
- Community Medicine Department, Isfahan University of Medical Sciences, Isfahan, Iran
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Endocrine role of bone in the regulation of energy metabolism. Bone Res 2021; 9:25. [PMID: 34016950 PMCID: PMC8137703 DOI: 10.1038/s41413-021-00142-4] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 12/20/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023] Open
Abstract
Bone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function. Recently, an increasing number of studies have characterized the significance of bone as an endocrine organ, suggesting that bone-derived factors regulate local bone metabolism and metabolic functions. In addition, these factors can regulate global energy homeostasis by altering insulin sensitivity, feeding behavior, and adipocyte commitment. These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis, treatment, and prevention of metabolic diseases such as osteoporosis, obesity, and diabetes mellitus. In this review, we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
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Hetemäki N, Mikkola TS, Tikkanen MJ, Wang F, Hämäläinen E, Turpeinen U, Haanpää M, Vihma V, Savolainen-Peltonen H. Adipose tissue estrogen production and metabolism in premenopausal women. J Steroid Biochem Mol Biol 2021; 209:105849. [PMID: 33610799 DOI: 10.1016/j.jsbmb.2021.105849] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 02/03/2021] [Accepted: 02/07/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Although the ovaries produce the majority of estrogens in women before menopause, estrogen is also synthesized in peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated in subcutaneous and femoro-gluteal regions, is estrogen-mediated, but the significance of estrogen synthesis in AT of premenopausal women is poorly understood. DESIGN AND METHODS Serum and subcutaneous and visceral AT homogenates from 28 premenopausal women undergoing non-malignant surgery were analyzed for estrone, estradiol, and serum estrone sulfate (E1S) concentrations with liquid chromatography-tandem mass spectrometry. Isotopic precursors were used to measure enzyme activities of estrone-producing steroid sulfatase and estradiol-producing 17β-hydroxysteroid dehydrogenases (17β-HSD). Messenger RNA (mRNA) expression levels of genes for estrogen-metabolizing enzymes were analyzed using real-time reverse transcription quantitative polymerase chain reaction. RESULTS While estradiol was the predominant circulating active estrogen, estrone dominated in AT, with a higher concentration in visceral than subcutaneous AT (median, 2657 vs 1459 pmol/kg; P = 0.002). Both AT depots converted circulating E1S to estrone, and estrone to estradiol. Median levels of estrone were five to ten times higher in subcutaneous and visceral AT than in serum (P < 0.001) and the estradiol level in visceral AT was 1.3 times higher than in serum (P < 0.005). The local estrone concentration in visceral AT correlated positively with mRNA expression of estrone-producing enzyme aromatase (r = 0.65, P = 0.003). Waist circumference correlated positively with increased estradiol production in subcutaneous AT (r = 0.60, P = 0.039). CONCLUSIONS Premenopausal AT demonstrated high estrogenic enzyme activity and considerable local estrogen concentrations. This may be a factor promoting female-typical AT distribution in premenopausal women.
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Affiliation(s)
- Natalia Hetemäki
- Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland; Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland
| | - Tomi S Mikkola
- Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland; Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland
| | - Matti J Tikkanen
- Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland; Heart and Lung Center, University of Helsinki and Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland
| | - Feng Wang
- Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland
| | - Esa Hämäläinen
- Department of Clinical Chemistry, University of Helsinki, FIN-00029 HUS, Helsinki, Finland
| | - Ursula Turpeinen
- HUSLAB, Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland
| | - Mikko Haanpää
- HUSLAB, Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland
| | - Veera Vihma
- Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, FIN-00014, Helsinki, Finland
| | - Hanna Savolainen-Peltonen
- Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, FIN-00029 HUS, Helsinki, Finland; Folkhälsan Research Center, University of Helsinki, FIN-00014, Helsinki, Finland.
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Yang C, Fang J, Sun X, Zhang W, Li J, Chen X, Yu L, Xia W, Xu S, Cai Z, Li Y. Prenatal exposure to organochlorine pesticides and infant growth: A longitudinal study. ENVIRONMENT INTERNATIONAL 2021; 148:106374. [PMID: 33476788 DOI: 10.1016/j.envint.2020.106374] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 12/11/2020] [Accepted: 12/29/2020] [Indexed: 06/12/2023]
Abstract
BACKGROUND The association between exposure to organochlorine pesticides (OCPs) and infant growth has been reported contradictorily in previous studies. Few studies have investigated the effects of prenatal exposure to OCPs on infant growth assessed longitudinally at multiple time points. OBJECTIVES The purpose of the study was to examine the associations between prenatal exposure to OCPs and infant growth at birth, 6, 12 and 24 months of age, and further to explore the potential sex-specific effects. METHODS The study population included 1039 mother-infant pairs who participated in a birth cohort study in Wuhan, China. The weight, length and body mass index (BMI) z-score of infants were measured and calculated at birth, 6, 12 and 24 months of age. The overweight status was defined as BMI z-score ≥ 85th percentile according to the standard of World Health Organization. The concentrations of OCPs were measured in cord serum, including hexachlorocyclohexanes (HCHs, consisted of α-HCH, β-HCH, and γ-HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolites: p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE). Generalized linear models were applied to estimate the associations of cord OCPs with infant growth parameters. A group-based semiparametric mixture model was used to estimate growth patterns of infants. Linear-mixed growth curve models were used to examine relationships between predicted growth trajectories and prenatal exposure to OCPs. Weighted quantile sum regression (WQSR) analyses were used to estimate the mixture effects of OCPs on infant growth. RESULTS Higher cord serum β-HCH concentrations were associated with higher BMI z-score at 12 [β = 0.07, 95%CI: 0.01, 0.13] and 24 months of age [β = 0.08, 95% CI: 0.02, 0.14]. Similar patterns were observed for relationships of γ-HCH [β = 0.04, 95%CI: 0.01, 0.07] and p,p'-DDT [β = 0.03, 95% CI: 0.00, 0.06] with BMI z-score at 6 and 12 months of age, respectively. However, higher cord serum p,p'-DDE concentrations were associated with a reduction of BMI z-score at 6 months of age [β = -0.07, 95% CI: -0.12, -0.01]. Cord serum β-HCH was also positively associated with the risk of overweight at 12 months of age [RR = 1.16, 95% CI (1.02, 1.33), for the medium vs the lowest tertile]. Among girls, the effects of β-HCH on BMI z-score and overweight status were stronger than boys at 12 and 24 months of age. No statistically significant relationships of other OCPs with infant growth were observed. CONCLUSIONS Prenatal exposure to β-HCH was associated with increased BMI z-score and higher risk of overweight status in infants especially at 12 and 24 months of age, which seemed to be stronger in girls.
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Affiliation(s)
- Chenhui Yang
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Jing Fang
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
| | - Xiaojie Sun
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Wenxin Zhang
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Juxiao Li
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Xiaomei Chen
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Ling Yu
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Wei Xia
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Shunqing Xu
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China
| | - Zongwei Cai
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
| | - Yuanyuan Li
- State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China.
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Lozi AA, Pinto da Matta SL, Sarandy MM, Silveira Alves de Melo FC, Araujo DC, Novaes RD, Gonçalves RV. Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:8853172. [PMID: 33628321 PMCID: PMC7895610 DOI: 10.1155/2021/8853172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 12/04/2020] [Accepted: 12/10/2020] [Indexed: 12/09/2022]
Abstract
Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.
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Affiliation(s)
- Amanda Alves Lozi
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | | | | | | | - Diane Costa Araujo
- Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil
| | - Rômulo Dias Novaes
- Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
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Lin IT, Lee MY, Wang CW, Wu DW, Chen SC. Gender Differences in the Relationships among Metabolic Syndrome and Various Obesity-Related Indices with Nonalcoholic Fatty Liver Disease in a Taiwanese Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18030857. [PMID: 33498329 PMCID: PMC7908550 DOI: 10.3390/ijerph18030857] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/13/2021] [Accepted: 01/17/2021] [Indexed: 02/07/2023]
Abstract
The incidence of nonalcoholic fatty liver disease
(NAFLD) is increasing worldwide, and it is strongly associated with metabolic syndrome (MetS) and some obesity-related indices. However, few studies have investigated gender differences in these associations. The aim of this study was to investigate associations among MetS and various obesity-related indices with NAFLD, and also look at gender differences in these associations. We enrolled participants who completed a health survey in southern Taiwan. MetS was defined according to the Adult Treatment Panel III for Asians, and the following obesity-related indices were calculated: body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), lipid accumulation product (LAP), body roundness index (BRI), conicity index (CI), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), triglyceride-glucose (TyG) index, and hepatic steatosis index (HSI). NAFLD was diagnosed when hepatic steatosis was noted on a liver ultrasound. A total of 1969 (764 men and 1205 women) participants were enrolled. Multivariable analysis showed that both male and female participants with MetS, high BMI, high WHtR, high WHR, high LAP, high BRI, high CI, high VAI, high BAI, high AVI, high TyG index, and high HSI were significantly associated with NAFLD. In addition, the interactions between MetS and gender, WHR and gender, LAP and gender, and TyG index and gender on NAFLD were statistically significant. Among these obesity-related indices, HSI and LAP had the greatest area under the curve in both men and women. Furthermore, stepwise increases in the number of MetS components and the values of indices corresponding to the severity of NAFLD were noted. In conclusion, our results demonstrated significant relationships between MetS and obesity-related indices with NAFLD, and also stepwise increases in the number of MetS components and the values of indices with the severity of NAFLD. MetS, WHR, LAP, and TyG index were associated with NAFLD more obviously in women than in men.
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Affiliation(s)
- I-Ting Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (I-T.L.); (M.-Y.L.)
| | - Mei-Yueh Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (I-T.L.); (M.-Y.L.)
| | - Chih-Wen Wang
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan; (C.-W.W.); (D.-W.W.)
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Da-Wei Wu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan; (C.-W.W.); (D.-W.W.)
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Szu-Chia Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan; (C.-W.W.); (D.-W.W.)
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7-8036783 (ext. 3440); Fax: +886-7-8063346
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Rosenfield RL, Cooke DW, Radovick S. Puberty in the Female and Its Disorders. SPERLING PEDIATRIC ENDOCRINOLOGY 2021:528-626. [DOI: 10.1016/b978-0-323-62520-3.00016-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Dalvi P, Loganathan N, Mcilwraith EK, Tran A, Belsham DD. Hypothalamic Cell Models. CELLULAR ENDOCRINOLOGY IN HEALTH AND DISEASE 2021:27-77. [DOI: 10.1016/b978-0-12-819801-8.00002-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Cheon YP, Ko C, Lee KH. Assessment of Adipocyte Differentiation and Maturation-related Gene Expression in the Epididymal Fat of Estrogen Receptor α Knockout (ERαKO) Mouse during Postnatal Development Period. Dev Reprod 2020; 24:287-296. [PMID: 33537515 PMCID: PMC7837422 DOI: 10.12717/dr.2020.24.4.287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 11/17/2020] [Accepted: 11/28/2020] [Indexed: 01/14/2023]
Abstract
The absence of functional estrogen receptor α (Esr1) results in an
overgrowth of the epididymal fat, as observed in estrogen receptor α
knockout (ERαKO) mouse. The present research was aimed to evaluate
expression of various molecules associated with adipocyte differentiation and
maturation in the epididymal fat of ERαKO mouse at several postnatal ages
by using quantitative real-time polymerase chain reaction. The highest
transcript levels of all molecules were detected at 12 months of postnatal age,
except leptin which the mRNA level was increased at 5 months of age and was
unchanged until 12 months of age. The expression levels of CCAAT enhancer
binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were
decreased at 5 months of age but increased at about 8 months of age. The mRNA
levels of Cebp gamma and sterol regulatory element binding transcription factor
1 remained steady until 8 months of age. Continuous increases of transcript
levels during postnatal period were found in Cebp beta, estrogen receptor (ER)
beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1.
The increases of peroxisome proliferator-activated receptor gamma and
adiponectin mRNA levels were detected as early as 8 months of age. The levels of
fatty acid synthase and resistin transcript at 5 and 8 months of age were lower
than that at 2 months of age. These findings show the aberrant expression
patterns of genes related to adipocyte differentiation and maturation in the
postnatal epididymal fat pad by the disruption of ER alpha function.
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Affiliation(s)
- Yong-Pil Cheon
- Division of Development and Physiology, Department of Biotechnology, CDPR, Institute for Basic Science, Sungshin Women University, Seoul, 02844 Korea
| | - CheMyong Ko
- Dept. of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA
| | - Ki-Ho Lee
- Dep. of Biochemistry and Molecular Biology, College of Medicine, Eulji University, Daejeon 34824, Korea
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Sun Z, Li D, Li Y, Chen D, Yu B, Yu J, Mao X, Zheng P, Luo Y, Luo J, He J. Effects of dietary daidzein supplementation on growth performance, carcass characteristics, and meat quality in growing-finishing pigs. Anim Feed Sci Technol 2020. [DOI: 10.1016/j.anifeedsci.2020.114591] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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