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

Abstract

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 < 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 < 0.0001), while the effect of VAT on systemic inflammation was mediated through higher kynurenine concentrations (indirect effect 6.4%, P < 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.

Keywords: aromatic amino acids; branched-chain amino acids; cardiometabolic risk markers; metabolites; subcutaneous adipose tissue; visceral adipose tissue.