Acute oral administration of L-leucine upregulates slow-fiber- and mitochondria-related genes in skeletal muscle of rats

Branched-chain amino acids promote both protein and mRNA synthesis through mechanistic target of rapamycin (mTOR) signaling. A previous report demonstrated that chronic branched-chain amino acid supplementation increased mitochondrial biogenesis in the skeletal muscle of middle-aged mice through activation of mTOR signaling. In this study, we hypothesized that the acute oral administration of L-leucine alone has the ability to alter the gene expression related to fiber type and metabolism in skeletal muscle of young rats through the activation of mTOR signaling. Although the gene expression of representative glycolytic enzymes (Hk2 and Eno3) was not altered, L-leucine administration (135 mg/100 g body weight) upregulated the expression of slow-fiber-related genes (Myh7, My13, and Tnni1) and a mitochondrial biogenesis-related gene (Ppargc1a) in the soleus and extensor digitorum longus muscles compared with the control. In addition, L-leucine treatment also upregulated the slow-fiber genes and mitochondrial gene expression in cultured C2C12 myotubes, whereas rapamycin inhibited the effects of L-leucine. However, L-alanine, L-phenylalanine, and L-valine treatment did not alter the expression of the fiber type- and metabolism-related genes as observed in L-leucine. Our results suggest that L-leucine may have the ability to alter skeletal muscle fiber type toward slow fiber and oxidative metabolism by upregulation of gene expression through mTOR signaling. (C) 2018 Elsevier Inc. All rights reserved.