2016年11月25日，美国临床内分泌权威杂志《The Journal of Clinical Endocrinology & Metabolism》在线发表了中国科学院上海生命科学研究院营养科学研究所尹慧勇组与上海交通大学附属仁济医院内分泌代谢科刘伟组合作的研究成果：Discovery of novel lipid profiles in PCOS: Do insulin and androgen oppositely regulate bioactive lipid production?该研究揭示了不同表型多囊卵巢综合征患者血清脂质谱的特点。

多囊卵巢综合征(PCOS)是在青春期及生育年龄妇女人群中常见的多系统综合征。最新流行病学调查研究显示，我国育龄妇女PCOS的发病率约为5.6%，并有逐年增高的趋势。PCOS主要表现为稀发排卵/不排卵、多囊卵巢、高雄激素血症，多伴有糖脂等多种代谢异常，显著增加罹患糖尿病、冠心病、子宫内膜癌等风险，严重影响女性生育健康。但目前有关多囊卵巢综合征的发病机制仍不清楚，临床干预手段也十分有限。

在该研究中，研究人员在初诊尚未进行药物干预的PCOS患者群中运用gc-ms/MS和LC-MS/MS等脂质组学技术检测了血清脂质谱，研究发现：肥胖伴脂肪肝的PCOS患者存在磷脂酰胆碱(PC)代谢异常，导致血清PC(16:0/18:0/18:1-18:2/20:4)升高，溶血磷脂酰胆碱(LPC)(16:0，18:0，18:1)下降，而非肥胖的PCOS患者变化不显著;肥胖的PCOS患者血清多不饱和脂肪酸(PUFAs)下降，而长链饱和脂肪酸(LSFAs)显著高于对照;PCOS患者血清中的PUFAs代谢产物(尤其是花生四烯酸的代谢产物)显著降低，这一现象在PCOS大鼠模型中也得到了验证。由于PCOS患者存在高雄激素和高胰岛素血症，推测雄激素和胰岛素对PUFAs代谢的不同作用导致了血清PUFAs代谢产物的改变。鉴于PGE2、PGF2a和PGI2在卵泡发育、成熟、排卵、受精和胚胎着床等生殖过程中的重要作用，该研究为深入探讨PCOS的发病机制和寻找新的治疗靶标提供了线索。

PCOS病人血清中脂代谢产物的变化谱图

原文摘要：Context:Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives play important roles in inflammation and reproduction, and both of these are tightly linked to PCOS and obesity.

Objective:To investigate serum lipid profiles in newly diagnosed PCOS patients using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity.

Design and Setting:32 newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was employed to validate the results of the human studies.

Main Outcome Measures:Serum lipid profiles, including phospholipids, free fatty acids (Ffas), and bioactive lipids, were analyzed using gas chromatography- and liquid chromatography-mass spectrometry.

Results:There was an elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid in obese PCOS patients compared with lean controls. Obese PCOS patients had decreased levels of PUFAs and increased levels of long-chain saturated fatty acids compared with lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean PCOS patients versus their respective controls.

Conclusions:Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in PCOS patients, particularly on the bioactive lipid metabolites derived from PUFAs. These novel clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity.