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循环神经调节蛋白4水平与多囊卵巢综合征的代谢、动脉粥样硬化及抗苗勒管激素特征之间的关联

Association between circulating neuregulin 4 levels and metabolic, aterogenic, and AMH profile of polycystic ovary syndrome.

作者信息

Kurek Eken Meryem, Sahin Ersoy Gülçin, Yayla Abide Cigdem, Sanverdi İlhan, Devranoglu Belgin, Kutlu Tayfun, Çevik Özge

机构信息

Department of Obstetric and Gyneacology-Aydın, Adnan Menderes University Medical Faculty , Aydın , Turkey.

Jinemed Private Hospital- İstanbul , Turkey.

出版信息

J Obstet Gynaecol. 2019 Oct;39(7):975-980. doi: 10.1080/01443615.2019.1581754. Epub 2019 May 7.

Abstract

Polycystic ovary syndrome (PCOS) is a metabolic disorder associated with obesity and energy metabolic system disturbances in adipose tissue. Neuregulin 4 (NRG4), which is secreted by adipose tissue, regulates energy metabolism. In the present study, we aimed to evaluate the association between serum NRG4 levels in obese and normal weight PCOS patients. This cross-sectional study was conducted at a tertiary hospital in Turkey from April to August 2017. We included 148 women who were divided into four groups as follows: 40 normal weight and 39 obese PCOS women diagnosed according to the Rotterdam criteria as well as 38 normal weight and 31 obese, age-matched, non-hyperandrogenemic women with a regular menstrual cycle (controls). Levels of serum NRG4, anti-Müllerian hormone (AMH), fasting blood glucose (FBG), insulin, and high-sensitivity C-reactive protein (hs-CRP); lipid and hormone profiles; insulin resistance indices [homeostasis model assessment of insulin resistance (HOMA-IR)];and anthropometric parameters were evaluated. Serum NRG4 levels were elevated in the normal weight PCOS group than in the control group. Moreover, serum NRG4 levels were higher in the obese PCOS group than in the normal weight PCOS and obese control groups ( < .01). Serum NRG4 levels were positively correlated with body mass index (BMI); waist/hip ratio; HOMA-IR; and levels of triglycerides, hs-CRP, FBG, insulin, AMH, and dehydroepiandrosterone sulphate. Multiple regression analyses revealed that serum NRG4 levels were independently associated with BMI. Obesity appears to be the most influential factor for NRG4 secretion in PCOS patients. Management of obesity may be a key factor for resolving PCOS-related metabolic abnormalities and fertility problems. Impact Sstatement PCOS is a dynamic syndrome with different clinical and metabolic features during the reproductive age. PCOS is associated with various metabolic abnormalities, such as insulin resistance (IR), glucose intolerance, dyslipidemia, and obesity (particularly visceral obesity) as well as long-term complications, such as type 2 diabetes and cardiovascular diseases. Neuregulin 4 (NRG4), which is secreted by adipose tissue, regulates energy metabolism. To the best of our knowledge, this was the first study investigating NRG4 levels in PCOS patients with different BMIs. Obesity appears to be the most influential factor for NRG4 secretion in these patients. Managing obesity may be a key factor for resolving PCOS-related metabolic abnormalities. Further research in PCOS is warranted to ameliorate obesity, and our study can provide basis for future studies investigating NRG4 levels in PCOS patients with different phenotypes as well as studies of gene polymorphisms, AMH, and infertility and can contribute to the elucidation of problems related to the pathophysiology of PCOS.

摘要

多囊卵巢综合征(PCOS)是一种与肥胖及脂肪组织能量代谢系统紊乱相关的代谢性疾病。脂肪组织分泌的神经调节蛋白4(NRG4)可调节能量代谢。在本研究中,我们旨在评估肥胖和正常体重的PCOS患者血清NRG4水平之间的关联。这项横断面研究于2017年4月至8月在土耳其的一家三级医院进行。我们纳入了148名女性,她们被分为四组:40名正常体重和39名肥胖的PCOS女性,根据鹿特丹标准诊断;以及38名正常体重和31名肥胖、年龄匹配、月经周期规律的非高雄激素血症女性(对照组)。评估了血清NRG4、抗苗勒管激素(AMH)、空腹血糖(FBG)、胰岛素和高敏C反应蛋白(hs-CRP)水平;血脂和激素谱;胰岛素抵抗指数[胰岛素抵抗稳态模型评估(HOMA-IR)];以及人体测量参数。正常体重的PCOS组血清NRG4水平高于对照组。此外,肥胖的PCOS组血清NRG4水平高于正常体重的PCOS组和肥胖对照组(<0.01)。血清NRG4水平与体重指数(BMI)、腰臀比、HOMA-IR以及甘油三酯、hs-CRP、FBG、胰岛素、AMH和硫酸脱氢表雄酮水平呈正相关。多元回归分析显示,血清NRG4水平与BMI独立相关。肥胖似乎是PCOS患者NRG4分泌的最有影响因素。控制肥胖可能是解决PCOS相关代谢异常和生育问题的关键因素。影响声明:PCOS是一种在生殖年龄具有不同临床和代谢特征的动态综合征。PCOS与各种代谢异常相关,如胰岛素抵抗(IR)、葡萄糖不耐受、血脂异常和肥胖(尤其是内脏肥胖)以及长期并发症,如2型糖尿病和心血管疾病。脂肪组织分泌的神经调节蛋白4(NRG4)可调节能量代谢。据我们所知,这是第一项研究不同BMI的PCOS患者中NRG4水平的研究。肥胖似乎是这些患者NRG4分泌的最有影响因素。控制肥胖可能是解决PCOS相关代谢异常的关键因素。有必要对PCOS进行进一步研究以改善肥胖,我们的研究可为未来研究不同表型的PCOS患者的NRG4水平以及基因多态性、AMH和不孕症的研究提供基础,并有助于阐明与PCOS病理生理学相关的问题。

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