Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics

Glueck, Charles J.; Goldenberg, Naila

doi:10.1016/j.metabol.2018.11.002

Cited by 300 publications

(224 citation statements)

References 170 publications

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“…This phenomenon is consistent with the clinic findings, which indicated that metformin alone does not increase the risk of hypoglycemia in diabetic patients [34]. Hence, metformin could be administered to nondiabetic patients, such as patients with fatty liver [35] and polycystic ovary syndrome (PCOS) [36], without causing hypoglycemia. Moreover, clinical studies have suggested that metformin has a protective effect on β-cells, independent of its hypoglycemic effect [37].…”

Section: Discussionsupporting

confidence: 88%

Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in β-Cells through the Activation of GPR40-PLC-IP3 Pathway

Shen

Fan

et al. 2019

Journal of Diabetes Research

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Background and Purpose. Metformin, a widely used antidiabetic drug, has been shown to have anti-inflammatory properties; nevertheless, its influence on β-cell meta-inflammation remains unclear. The following study investigated the effects of metformin on meta-inflammatory in β-cells and whether the underlying mechanisms were associated with the G protein-coupled receptor 40-phospholipase C-inositol 1, 4, 5-trisphosphate (GPR40-PLC-IP3) pathway. Materials and Methods. Lipotoxicity-induced β-cells and the high-fat diet-induced obese rat model were used in the study. Results. Metformin-reduced lipotoxicity-induced β-cell meta-inflammatory injury was associated with the expression of GPR40. GPR40 was involved in metformin reversing metabolic inflammation key marker TLR4 activation-mediated β-cell injury. Furthermore, downstream signaling protein PLC-IP3 of GPR40 was involved in the protective effect of metformin on meta-inflammation, and the above process of metformin was partially regulated by AMPK activity. In addition, the anti-inflammatory effects of metformin were observed in obese rats. Conclusion. Metformin can reduce lipotoxicity-induced meta-inflammation in β-cells through the regulation of the GPR40-PLC-IP3 pathway and partially via the regulation of AMPK activity.

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Section: Discussionsupporting

confidence: 88%

Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in β-Cells through the Activation of GPR40-PLC-IP3 Pathway

Shen

Fan

et al. 2019

Journal of Diabetes Research

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“…Obesity increased the expression of early complement pathway components in subcutaneous adipose tissue (40). Obesity has been reported to upregulate inflammatory adipokines and to induce IR, androgen production, and adipogenesis (41,42). Hence, proinflammatory follicular environment in PCOS could be amplified by obesity.…”

Section: Discussionmentioning

confidence: 99%

TMT Based Proteomic Analysis of Human Follicular Fluid From Overweight/Obese and Normal-Weight Patients With Polycystic Ovary Syndrome

Zhang

et al. 2019

Front. Endocrinol.

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Conclusion: In this proteomic study, a panel of proteins were found differentially expressed in the follicular fluid of PCOS. Inflammatory, immunological, and metabolic abnormalities were identified inside the intra-follicular environment, which could be aggravated by obesity. The identified proteins were correlated with follicular growth and may be considered as candidate biomarkers as well as therapeutic targets of PCOS.

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“…Since PCOS is associated with complex pathogenesis, the genes that have been identified for PCOS risk are related to the gonado- tropic regulatory axis, glucose and lipid metabolism, and cell cycle regulation [3,34]. The genes are located in the susceptibility loci and LHCGR, FSHR, INRS, THADA, HMGA2, RAB5B, SUOX, YAP, ZNF217 are included from the GWAS studies [20,35].…”

Section: Discussionmentioning

confidence: 99%

THADA_rs13429458 Minor Allele Increases the Risk of Polycystic Ovary Syndrome in Asian, but Not in Caucasian Women: A Systematic Review and Meta-Analysis

2019

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Polycystic ovary syndrome (PCOS) is a highly prevalent disease in young women that also features increased insulin resistance. Genetic factors have a strong relationship with the etiology of PCOS. We assessed whether carrying THADA rs13429458 is associated with the development of PCOS by meta-analysis and whether the association is influenced by ethnicity. Articles were searched using PubMed, EMBASE, Cochrane Library, Korean scientific database, and Chinese and Indian medical databases to identify all eligible studies for evaluating the association of THADA rs13429458 and PCOS risk. The association was assessed in five genetic random effects models including the allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Subgroup analyses stratified by ethnicity (Asians and non-Asians) were assessed. Nine articles were selected and 1 association analysis of Korea PCOS study met Hardy–Weinberg equilibrium criteria. A set of 38 224 PCOS women and 120 173 healthy women were included. The AG and RG showed heterogeneity in the overall and Asian subjects, but the other genetic model did not exhibit heterogeneity in all subjects. AG, RG, DG, and HMG, but not HTG, exhibited publication bias in total subjects but there was no publication bias in all genetic models among Asians and non-Asians. The overall effect of THADA_rs13429458 on PCOS risk showed significant positive associations in pooling 10 studies. In sub-group analysis only Asians, but not non-Asians, had a positive association (AG: OR=1.24, p=0.001; RG: OR=1.32, p=0.002; DG: OR, 1.70, p<0.00001; HMG: OR, 1.71, p=0.002; HTG: OR=1.34, p=0,006). In conclusions, young Asian women with the minor allele (C) for THADA rs13429458 were at increased risk of PCOS.

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Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics

Cited by 300 publications

References 170 publications

Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in β-Cells through the Activation of GPR40-PLC-IP3 Pathway

Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in β-Cells through the Activation of GPR40-PLC-IP3 Pathway

TMT Based Proteomic Analysis of Human Follicular Fluid From Overweight/Obese and Normal-Weight Patients With Polycystic Ovary Syndrome

THADA_rs13429458 Minor Allele Increases the Risk of Polycystic Ovary Syndrome in Asian, but Not in Caucasian Women: A Systematic Review and Meta-Analysis

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