Abstract
Abstract Background and objectives: Polycystic ovary syndrome (PCOS) displays a phenotype-dependent cardio-metabolic risk. By performing a systematic search of the literature, we aimed to summarize metabolomic signatures associated with obesity in PCOS women. Data sources and study eligibility criteria: We conducted a comprehensive search including: Embase, PubMed, and Web of Science until 31st of May 2019. We used the terms: metabolomics and polycystic ovary syndrome. We excluded the following papers: animal studies, studies that included only lean PCOS women, reviews, meta-analyses, results of interventional studies, those that did not apply metabolomic techniques. Results: The lipid signature in obese women with PCOS showed increased levels of free fatty acids (carnitine, adipic acid, linoleic acid, oleic acid) and lower levels of lysophosphatidylcholines and glycerolphosphocholine compared with non-obese PCOS women. Regarding carbohydrate metabolism, a decrease in citric and lactic acid levels characterized obese PCOS women. Decreased lactic acid in obese PCOS women suggests augmented insulin stimulated glucose muscle use in lean, but not in obese women. Considering amino acid metabolomic markers, valine, glycine, serine, threonine, isoleucine and lysine were higher in obese PCOS women. Patients with visceral obesity presented a diminished uptake of essential amino acids, BCAA, leucine and serine in the skeletal muscle. α-ketoglutarate was significantly higher in obese women with PCOS in comparison with lean women with PCOS, distinguishing these 2 subgroups of PCOS with high ‘predictive accuracy’. Limitations: Overall, a small number of studies have focused on the impact of obesity on the metabolic fingerprints of PCOS women. There is need for properly controlled, high-quality studies. Conclusions: There is compelling evidence of significant alterations in carbohydrate, lipid, and amino acid metabolism in women with PCOS and obesity. Metabolomics may identify new metabolic pathways involved in PCOS and improve our understanding of the complex relation between PCOS and obesity in order to personalize PCOS therapy.
Highlights
Rationale and background Polycystic ovary syndrome (PCOS) is a heterogenous disease affecting between 6 to 20% of women at reproductive age, with a variable cardio-metabolic risk [1]
By performing a systematic search of the literature, we aimed to summarize metabolomic pathways and biomarkers associated with obesity in women with PCOS
Carbohydrate metabolism in obese PCOS GC-mass spectrometry (MS)-based metabolomics conducted by Escobar-Morreale et al and recently by Troisi et al identified increased levels of lactic acid in lean and overweight PCOS women and decreased levels in obese PCOS women, suggesting an augmented muscle insulin-stimulated glucose use in lean, but not obese women with PCOS [19, 20]
Summary
Rationale and background Polycystic ovary syndrome (PCOS) is a heterogenous disease affecting between 6 to 20% of women at reproductive age, with a variable cardio-metabolic risk [1]. Metabolomic profiling in PCOS has made its first steps in the early 2012, with few studies that focused on characterization of the metabolomic signature of lipid metabolism, hormone biosynthesis, medical therapies, and assisted reproduction outcomes [6,7,8,9,10]. Objectives: By performing a systematic search of the literature, we aimed to summarize metabolomic pathways and biomarkers associated with obesity in women with PCOS. Polycystic ovary syndrome (PCOS) displays a phenotype-dependent cardio-metabolic risk. By performing a systematic search of the literature, we aimed to summarize metabolomic signatures associated with obesity in PCOS women. Decreased lactic acid in obese PCOS women suggests augmented insulin stimulated glucose muscle use in lean, but not in obese women.
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