Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway

Abstract

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1-4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults.

Keywords: PGC-1α; aging; kynurenine; physical activity; skeletal muscle.

Fig. 1.

A and B: fold changes post- versus preexercise training in expression of skeletal muscle transcription coactivators PGC-1α, PPARα, and PPARδ (A) and skeletal muscle gene expression of KAT isoforms 1–4 (B). C: percent change in plasma metabolites KYNA and QUIN post- versus preexercise training. PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1α; PPAR, peroxisome proliferator-activated receptor; KAT, kynurenine amino transferase; KYNA, kynurenic acid; QUIN, quinolinic acid. Repeated-measures ANOVA; n = 25. Error bars represent SE. **P ≤ 0.01, ***P ≤ 0.001.