Branched-chain and aromatic amino acids related to visceral adipose tissue impact metabolic health risk markers

Context: Visceral (VAT) and subcutaneous adipose tissue (SAT) function as endocrine organs capable of influencing metabolic health across adiposity levels. Objective: 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 < 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 standard deviation 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 to 11%, p=0.02 to <0.0001), while the effect of VAT on systemic inflammation was mediated through higher kynurenine concentrations (indirect effect 6.4%, p<0.0001). Conclusions: 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.