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Context Visceral (VAT) and subcutaneous adipose tissue (SAT) function as endocrine organs capable of influencing metabolic health across adiposity levels. Objective We aimed to investigate whether metabolites associated with VAT and SAT impact metabolic health through metabolite concentrations. Methods Analyses are based on 1790 participants from the population-based Rhineland Study. We assessed plasma levels of methionine (Met), branched-chain amino acids (BCAA), aromatic amino acids (AAA), and their metabolic downstream metabolites with liquid chromatography-mass spectrometry. VAT and SAT volumes were assessed by magnetic resonance imaging (MRI). Metabolically healthy and unhealthy phenotypes were defined using Wildman criteria. Results Metabolically unhealthy participants had higher concentrations of BCAA than metabolically healthy participants (P &amp;lt; 0.001). In metabolically unhealthy participants, VAT volumes were significantly associated with levels of L-isoleucine, L-leucine, indole-3-lactic acid, and indole-3-propionic acid (in log SD units: β = 0.16, P = 0.003; β = 0.12, P = 0.038; β = 0.11, P = 0.035 and β = −0.16, P = 0.010, respectively). Higher concentrations of certain BCAA and AAA-downstream metabolites significantly increased the odds of cardiometabolic risk markers. The relation between VAT volume and cardiometabolic risk markers was mediated by BCAA (indirect effects 3.7%-11%, P = 0.02 to &amp;lt; 0.0001), while the effect of VAT on systemic inflammation was mediated through higher kynurenine concentrations (indirect effect 6.4%, P &amp;lt; 0.0001). Conclusion Larger volumes of VAT in metabolically unhealthy individuals are associated with altered concentrations of circulating BCAA and AAA-downstream metabolites, increasing the odds of cardiometabolic risk markers. This suggests that these metabolites are involved in the mechanisms that underlie the relationship of abdominal VAT with metabolic health.

Branched-Chain and Aromatic Amino Acids Related to Visceral Adipose Tissue Impact Metabolic Health Risk Markers