Phenyllactic Acid is Physiologically Released from Skeletal Muscle and Contributes to the Beneficial Effects of Physical Exercise in Humans

Abstract

Methods We studied acute exercise- and training-induced changes in plasma metabolites in sedentary subjects with overweight (8 male, 14 female) participating in an eight-week supervised training program flanked by two acute endurance exercise sessions. Plasma metabolites were quantified using LC- and CE-MS. In a separate study (n=9 lean males), we assessed metabolite fluxes over the leg using arterial and venous catheters. Functional analyses were performed in primary blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) or the saturated fatty acid palmitate. Results The amino acid breakdown products 3-phenyllactic acid (PLA), 4-hydroxyphenyllactic acid and indolelactic acid were increased after both acute exercise and training. All three aromatic lactic acids, which so far mainly received attention as bacterial metabolites, exhibited an efflux from the leg. PLA showed the largest increase after both acute exercise and training, of 57% and 20% respectively. The magnitude of the acute exercise-induced increase in PLA correlated with a decrease in subcutaneous adipose tissue volume and an improvement in insulin sensitivity over the course of the intervention. Furthermore, both isomers, D and L-PLA, counteracted inflammatory cytokine production in PBMCs. Conclusions/interpretation Our findings indicate that PLA is physiologically released from skeletal muscle and can contribute to the anti-inflammatory effects of exercise as well as to individual difference in the response to lifestyle interventions in humans. PLA and potentially, aromatic lactic acids in general may be particularly relevant metabolic regulators because they can be produced both endogenously and by the microbiome.