Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS
Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS
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DOI：
10.1373/clinchem.2011.176396
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发表时间：
2012-06-01
影响因子：
9.3
通讯作者：
Correig, Xavier
中科院分区：
文献类型：
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作者：
Escobar-Morreale, Hector F.;Samino, Sara;Correig, Xavier
背景：腹部脂肪和肥胖影响多囊卵巢综合征（PCOS）与胰岛素抵抗和糖尿病的关联。我们的目的是表征与多囊卵巢综合征和肥胖相关的中间代谢表型。方法：我们采用非靶向GC-MS代谢组学方法对36例多囊卵巢综合征患者和39例无雄激素过量的对照女性的血浆样本进行分析，这些患者的年龄、体重指数和肥胖频率相匹配。结果：与对照组相比，PCOS患者存在高胰岛素血症和胰岛素抵抗。肥胖多囊卵巢综合征患者血浆长链脂肪酸（如亚油酸、油酸和甘油）的增加表明脂肪分解增加，可能继发于脂肪组织胰岛素作用受损。相反，非肥胖多囊卵巢综合征患者的代谢特征是外周组织脂肪分解受到抑制，葡萄糖利用增加（乳酸浓度增加），多囊卵巢综合征患者整体上显示2-酮异己酸和丙氨酸浓度下降，表明支链氨基酸用于蛋白质合成，而不是用于糖异生。这些代谢过程需要有效的胰岛素信号传导;因此，胰岛素抵抗在这些女性的所有组织中并不普遍，不同的机制可能导致了她们的高胰岛素血症。多囊卵巢综合征还与α -生育酚和胆固醇浓度降低有关，与肥胖无关。结论：受肥胖强烈影响的代谢异质性是多囊卵巢综合征的潜在原因。在设计这种流行疾病的诊断和治疗策略时，应考虑到非肥胖多囊卵巢综合征妇女在没有普遍胰岛素抵抗的情况下可能发生高胰岛素血症的可能性。(C) 2012美国临床化学学会
BACKGROUND: Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity.METHODS: We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity.RESULTS: Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased alpha-tocopherol and cholesterol concentrations irrespective of obesity.CONCLUSIONS: Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder. (C) 2012 American Association for Clinical Chemistry