Disruption of Branched-Chain Amino Acid Catabolism Impairs Rat Myoblast Survival and Differentiation

This study investigates the role of branched-chain amino acid catabolism in rat myoblast differentiation. The branched-chain amino acids (BCAAs), particularly leucine, have been consistently shown to possess anabolic and anti-catabolic effects in regards to skeletal muscle hypertrophy and skeletal muscle differentiation. Metabolites of branched-chain amino acid catabolism have also been shown to induce similar effects, suggesting that production of these metabolites may mediate the effect of BCAA presence. Our study confirms that the leucine metabolite alpha-ketoisocaproate (KIC) can positively regulate rat myoblast differentiation, and ameliorate conditions of leucine deprivation. Furthermore, we demonstrate that impairing the enzymes BCAT2 and BCKD that produce KIC and other BCAA metabolites results in impaired myoblast differentiation and proliferation. Lastly, we show that myoblasts that have impaired BCAA catabolism become apoptotic and programmed for cell death. Conclusively, our findings demonstrate that BCAA catabolism is an essential process that facilitates myoblast survival and differentiation.