Abstract 274: Defective Branched Chain Amino Acid Catabolism Impairs Exercise Endurance

Abstract

The branched chain amino acids (BCAA), leucine, isoleucine and valine, are essential for mammalians, and they play a positive role in exercise capacity, muscle development, and a lean body phenotype. BCAA supplementation is commonly paired with exercise in order to promote muscle growth, increase resistance to fatigue and reduce muscle soreness. On the other hand, elevated serum BCAA is strongly and positively correlated with the development of insulin resistance, coronary heart disease, and type II diabetes, and is predictive of patient response to therapeutics and intervention outcomes. We have previously shown that defective BCAA catabolism in mice impaired glucose metabolism in the heart and increased susceptibility to stress-induced cardiac damage. In this study we sought to determine the effects of elevated BCAA levels on skeletal muscle performance and response to exercise training using mouse models with systemically elevated BCAA levels. Supplementation of BCAA (1.5mg/g bodyweight/day, ratio of Leu:Ile:Val = 1.5:0.8:1) was administered to mice with impairment of BCAA catabolism due to the deletion of mitochondrial-localized protein phosphatase 2C (KO), a key enzyme in activating BCAA catabolism, and their littermate controls (CON). Mice were subjected to one week of daily exercise training via forced treadmill running and an exercise capacity test was performed at the beginning and end of training. Baseline maximum running time was decreased in the KO compared to CON (mean 73.4 and 82.5 min, respectively). One week of training resulted in increased exercise capacity in CON with an attenuated increase in KO mice (mean 136 and 112 min, respectively). BCAA supplementation did not further improve exercise capacity in CON (mean 131 min) and abrogated the response to training in KO (mean 70.1 min). Reduced exercise capacity positively correlated with elevated serum BCAA levels. Additionally, KO supplemented with BCAAs demonstrated elevated serum succinate, alanine and glutamate levels, which are metabolic markers of physiological stress. We conclude that short term supplementation of BCAA has no benefit for exercise capacity and accumulation of BCAAs has a negative effect on endurance exercise capacity.