Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS

H. F. Escobar-Morreale, S. Samino, M. Insenser, M. Vinaixa, M. Luque-Ramirez, M. A. Lasuncion, X. Correig
2012 Clinical Chemistry  
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
more » ... mic 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 ␣-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. Polycystic ovary syndrome (PCOS) 6 is the most prevalent endocrine disorder in women of fertile age (1 ). PCOS is characterized by androgen excess and is associated with metabolic disorders such as obesity, insulin resistance, and diabetes (2-4 ) . The occurrence of disorders of glucose tolerance and diabetes in women with PCOS appears to be mainly dependent on the association with insulin resistance, with obesity playing a major triggering role (5 ). Whether the increased risk of diabetes pertains to all patients of PCOS irrespective of obesity, or only to obese patients and nonobese patients with additional risk factors, is still matter of debate (6, 7 ). The application of hypothesis-free genomic and proteomic techniques to the study of PCOS confirmed the involvement of insulin resistance and low-grade chronic inflammation in its pathogenesis (8 ), but also revealed the participation of metabolic pathways related to iron metabolism, Wnt signaling, oxidative stress, immune function, and lipid metabolism in the pathogenesis of this prevalent disorder (8 -11 ). Recently introduced metabolomics aim at the identification and quantification of all metabolites in biological systems (12 ). Metabolites include a wide array of compound classes such as amino acids, lipids,
doi:10.1373/clinchem.2011.176396 pmid:22427353 fatcat:w6jnmbfyzrbopcxswfnupcacca