Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism

Abstract

It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

The Aging Metabolome—Biomarkers to Hub Metabolites

“…It has been well known that exercise results in a significant increase in TCA cycle intermediates [ 92,93 ] generated from both glucose and fatty acid oxidation. It has recently become clear that branched chain amino acids (BCAA) are a major source of TCA cycle intermediates [ 94,95 ] during exercise, and that BCAA catabolism is required during exercise. Therefore, it is clear that multiple carbon substrates including BCAA are mobilized to maintain TCA intermediates that play important metabolic and signaling roles.…”

Role of branched‐chain amino acid–catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis

“…Given the high ratio of BCKDK to BCKDH in the skeletal muscle, BCKDK is thought to play an effective role in regulating skeletal muscle metabolic homeostasis. Muscle-specific BCKDK KO mice displayed significantly increased BCAA catabolism with an increased abundance of branched-chain acylcarnitine that is responsible for the metabolic alterations in the muscle (63). Additionally, these mice had low skeletal muscle glycogen levels and lower adaptability to endurance training than control mice (63).…”

“…Muscle-specific BCKDK KO mice displayed significantly increased BCAA catabolism with an increased abundance of branched-chain acylcarnitine that is responsible for the metabolic alterations in the muscle (63). Additionally, these mice had low skeletal muscle glycogen levels and lower adaptability to endurance training than control mice (63). Furthermore, BCAA supplementation is required during protein restriction in musclespecific BCKDK KO mice for maintaining the myofibrillar proteins by sustaining mTOR activity and not by inhibiting autophagy (64).…”

Recent advances in clinical probiotic research for sport

“…In addition, L. plantarum PS128 substantially increased plasma branched-chain amino acids (BCAA; 24–69%; P ≤ 0.05) and elevated exercise performance (i.e., 30 s Wingate test and VO 2 MAX endurance test; P ≤ 0.05), as compared with placebo. BCAA's have been reported to play a role in fatigue reduction in endurance exercise and are important for homeostasis of muscle energy metabolism and energy index for adaptation to exercise training [ 8 ]. Together, these studies suggest a role in which certain probiotic strains may enhance energy harvesting, and have health-promotion, performance-improvement, and antifatigue effects.…”