Abstract
BACKGROUND: Visceral fat (VF) increases risk for cardiometabolic disease (CMD), the leading cause of morbidity and mortality. Variations in the circulating metabolome predict the risk for CMD but whether or not this is related to VF is unknown. Further, CMD is now also present in adolescents, and the relationships between VF, circulating metabolome, and CMD may vary between adolescents and adults. METHODS: With an aim to add understanding to the metabolic variations in visceral obesity, we tested associations between VF, measured directly with magnetic resonance imaging, and 228 fasting serum metabolomic measures, quantified with nuclear magnetic resonance spectroscopy, in 507 adults (36-65 years) and 938 adolescents (12-18 years). We further utilized data from published studies to estimate similarities between VF and CMD-associated metabolic profiles. RESULTS: Here we show that VF, independently of body mass index (BMI) or subcutaneous fat, is associated with triglyceride-rich lipoproteins, fatty acids, and inflammation in both adults and adolescents, whereas the associations with amino acids, glucose, and intermediary metabolites are significant in adults only. BMI-adjusted metabolomic profile of VF resembles those predicting type 2 diabetes in adults (R (2) = 0.88) and adolescents (R (2) = 0.70), and myocardial infarction in adults (R (2) = 0.59) and adolescents (R (2) = 0.40); this is not the case for ischemic stroke (adults: R (2) = 0.05, adolescents: R (2) = 0.08). CONCLUSIONS: Visceral adiposity is associated with metabolomic profiles predictive of type 2 diabetes and myocardial infarction even in normal-weight individuals and already in adolescence. Targeting factors contributing to the emergence and maintenance of these profiles might ameliorate their cumulative effects on cardiometabolic health.