Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women, with clinical manifestations of anovulation and hyperandrogenaemia. The treatment of PCOS mainly focuses on improving clinical symptoms, such as insulin sensitivity or menstrual disorder, through drug treatment. However, due to the pathogenesis diversity of PCOS, there is still a lack of effective treatment in clinics. Metabolic disorder is the key factor in the occurrence of PCOS. Brown adipose tissue (BAT) is a special adipose tissue in the human body that can participate in metabolic balance by improving heat production. BAT has been demonstrated to be an important substance involved in the metabolic disorder of PCOS. Although increasing evidence indicates that BAT transplantation can improve the symptoms of PCOS, it is difficult to achieve BAT transplantation at present due to technical limitations. Stimulation of BAT activation by exogenous substances may be an effective alternative therapy for PCOS. In this study, we investigated the effects of Irisin on dehydroepiandrosterone (DHEA)-induced PCOS in mice and evaluated the effect of Irisin on serum hormone levels and changes in body temperature, body weight and ovarian morphology. In our study, we found that Irisin can enhance the thermogenesis and insulin sensitivity of PCOS mice by activating the function of BAT. In addition, Irisin treatment can correct the menstrual cycle of PCOS mice, improve the serum steroid hormone disorder status, and reduce the formation of ovarian cystic follicles. In conclusion, our results showed that Irisin treatment significantly improved the metabolic disorder of PCOS and may provide a new and alternative therapy for the treatment of this pathology.
Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive intrauterine pregnancies that are clinically established early in pregnancy. To date, the etiology and underlying mechanisms of RSA remain unclear. It is widely thought that the impairment of decidualization is inclined to induce subsequent pregnancy failure and leads to the dysregulation of extra-villous trophoblast invasion and proliferation through maternal–fetal cross talk. However, the mechanism of decidualization in RSA has yet to be understood. In our study, we demonstrate that decidual samples from RSA patients have significantly higher insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and lower TGF-β1 levels compared to healthy controls. In addition, the overexpression of IGF2BP3 in human endometrial stromal cells (hESCs) can lead to the impairment of decidualization in vitro-induced model and the abnormal cell cycle regulation. Furthermore, TGF-β1 and MMP9 levels were greatly increased after decidualization, whereas IGF2BP3 overexpression inhibited endometrial mesenchymal decidualization by downregulating TGF-β1, impeding maternal–fetal interface cytokine cross talk, and limiting the ability of trophoblast invasion. In conclusion, our investigation first demonstrates that abnormal elevation of IGF2BP3 in the pregnant endometrium leads to the impairment of decidualization and abnormal trophoblast invasion, thereby predisposing individuals to RSA.
Aims/Introduction: To explore the potential role of irisin in the outcomes of newly diagnosed prediabetes. Materials and Methods: Data were obtained from the Guiyang subcenter of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 2,530 participants had newly diagnosed prediabetes at baseline and completed follow up. The nested 1:1 case-control study included 161 participants who developed diabetes mellitus at follow up, and 161 age-and sex-matched controls. The follow-up study included 86 matched case-control pairs. Fasting serum irisin levels were measured using enzyme-linked immunosorbent assay. Results: Baseline serum irisin levels were higher in the cases than in the controls (P = 0.002); high baseline serum irisin levels were an independent risk factor for the development of diabetes (odds ratio 1.235, 95% confidence interval 1.025-1.488). After adjustment for age, sex, body mass index, glycated hemoglobin (HbA1c), smoking, exercise, and family history of diabetes, subjects in the highest quartile of irisin levels had a higher risk of diabetes than those in the lowest quartile (odds ratio 3.065, 95% confidence interval 1.511-6.218). The extent of decrease in irisin levels during follow-up was greater in the cases than in the controls (P < 0.001). Baseline serum irisin levels were positively correlated with the extent of decrease in irisin during follow-up (r = 0.773, P < 0.001). After adjustment for confounding factors, subjects with a decrease of irisin above the median had much higher risk for diabetes (odds ratio 5.077, 95% confidence interval 2.112-12.206). Conclusions: Irisin might play an important role in the outcomes of newly diagnosed prediabetes in adults in Guiyang, and can predict the risk for developing diabetes in these individuals.
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