Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?
Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?
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多囊卵巢综合征中新型脂质谱的发现：胰岛素和雄激素是否相反地调节生物活性脂质的产生？
DOI：
10.1210/jc.2016-2692
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发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Liu W
中科院分区：
文献类型：
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作者：
Li S;Chu Q;Ma J;Sun Y;Tao T;Huang R;Liao Y;Yue J;Zheng J;Wang L;Xue X;Zhu M;Kang X;Yin H;Liu W
我们发现多囊卵巢综合征患者的血脂水平发生了变化。肥胖和代偿性高胰岛素血症促进了花生四烯酸和其他PUFA的代谢，而雄激素则具有抑制作用。多囊卵巢综合征（PCOS）是一种复杂的综合征，表现为内分泌/代谢紊乱的临床特征，包括高胰岛素血症和高雄激素血症。多不饱和脂肪酸（PUFA）及其衍生物与PCOS和肥胖密切相关，在炎症和生殖中起着重要作用。本研究旨在利用脂质组学研究新诊断的PCOS患者的血脂谱，并将这些特征与PCOS和肥胖相关的高胰岛素血症和高雄激素血症相关联。32例新诊断的PCOS患者和34例对照者被分为肥胖和消瘦两个亚组。使用多囊卵巢综合症大鼠模型来验证人体研究的结果。采用气相色谱-质谱法（MS）和液相色谱-质谱法（LC-MS）分析血清脂质谱，包括磷脂、游离脂肪酸（FFA）和生物活性脂质。与瘦型对照组相比，肥胖型PCOS患者的磷脂酰胆碱水平升高，溶血磷脂水平降低。肥胖PCOS患者与瘦对照组相比，PUFA水平降低，长链饱和脂肪酸水平升高。与各自的对照组相比，肥胖对照组中花生四烯酸下游的血清生物活性脂质增加，但肥胖和瘦型PCOS患者中花生四烯酸下游的血清生物活性脂质减少。PCOS患者表现出异常水平的磷脂酰胆碱，游离脂肪酸和多不饱和脂肪酸代谢产物。循环中的胰岛素和雄激素可能对PCOS患者的脂质谱产生相反的影响，特别是对来自PUFA的生物活性脂质代谢产物。这些临床观察保证了对PCOS和肥胖的分子机制和临床意义的进一步研究。
We found serum lipid profiles changed in women with PCOS. Obesity and compensatory hyperinsulinemia promoted the metabolism of arachidonic acid and other PUFAs, whereas androgen had an inhibitory effect. 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, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography–mass spectrometry (MS) and liquid chromatography–MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity.