Metabolic syndrome comprises a series of health conditions, such as increased blood pressure, high blood sugar, excess abdominal fat, and altered circulating cholesterol or triglyceride levels. A fast growing number of affected individuals are at an increased risk of heart disease, stroke and type-2 diabetes. Obesity, especially build-up of visceral fat, is a recognized major risk factor for the development of metabolic syndrome. However, our understanding of the mechanistic links and biomarkers that associate visceral fat with the development of conditions underlying metabolic syndrome is still inadequate. In a recent paper published in the Biochemical Journal [Biochem. J. (2018) 475, 1019–1035], Candi et al. address this lack of knowledge, performing high-throughput metabolomics analysis of visceral fat isolated from obese individuals, with and without metabolic syndrome, and non-obese healthy controls. The authors identify alterations in metabolic pathways that distinguish pathologically from healthy obese subjects. They identify metabolic cues that point to oxidative and inflammatory burden as the leitmotifs of metabolic syndrome. Of particular interest is the identification of increased metabolism of γ-glutamyl amino acids and plasmalogens in pathological obesity. γ-glutamyl amino acids, generated through the transfer of a γ-glutamyl moiety from glutathione to an amino acid acceptor, are involved in glutathione metabolism and the response to oxidative stress, whereas plasmalogens, a poorly studied class of phospholipids, are known contributors to insulin resistance and hypertension. Both classes of metabolites are intriguing candidate biomarkers that warrant further investigation.

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