Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of the total body weight, plays important roles in exercise, energy expenditure, and glucose/amino acid usage—processes that are modulated by various amino acids and their metabolites. In this review, we address the metabolism and function of amino acids in the skeletal muscle. The expression of PGC1α, a transcriptional coactivator, is increased in the skeletal muscle during exercise. PGC1α activates branched-chain amino acid (BCAA) metabolism and is used for energy in the tricarboxylic acid (TCA) cycle. Leucine, a BCAA, and its metabolite, β-hydroxy-β-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. The metabolite of valine (another BCAA), β-aminoisobutyric acid (BAIBA), is increased by exercise, is secreted by the skeletal muscle, and acts on other tissues, such as white adipose tissue, to increase energy expenditure. In addition, several amino acid-related molecules reportedly activate skeletal muscle function. Oral 5-aminolevulinic acid (ALA) supplementation can protect against mild hyperglycemia and help prevent type 2 diabetes. β-alanine levels are decreased in the skeletal muscles of aged mice. β-alanine supplementation increased the physical performance and improved the executive function induced by endurance exercise in middle-aged individuals. Further studies focusing on the effects of amino acids and their metabolites on skeletal muscle function will provide data essential for the production of food supplements for older adults, athletes, and individuals with metabolic diseases.

This article is available online at http://www.jlr.org infl uences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle. Phospholipids are important structural components of membranes, and they infl uence a number of physical properties related to membrane function, including fl uidity, permeability, and the anchoring of membrane-related proteins. Because altering dietary fatty acids ( 1-3 ) and Abstract Exercise training infl uences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; however, the molecular mechanism of this infl uence on compositional changes is poorly understood. Peroxisome proliferator-activated receptor ␥ coactivator 1 ␣ (PGC-1 ␣ ), a nuclear receptor coactivator, promotes mitochondrial biogenesis, the fi ber-type switch to oxidative fi bers, and angiogenesis in skeletal muscle. Because exercise training induces these adaptations, together with increased PGC-1 ␣ , PGC-1 ␣ may contribute to the exercise-mediated change in phospholipid fatty acid composition. To determine the role of PGC-1 ␣ , we performed lipidomic analyses of skeletal muscle from genetically modified mice that overexpress PGC-1 ␣ in skeletal muscle or that carry KO alleles of PGC-1 ␣ . We found that PGC-1 ␣ affected lipid profi les in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC-1 ␣ was required for these alterations. Because phospholipid fatty acid composition

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Leucine is known to increase mTOR-mediated phosphorylation of 4EBP. In this study, leucine was administered to skeletal muscle-PGC-1α knockout mice. We observed attenuated 4EBP phosphorylation in the skeletal muscle, but not in the liver, of the PGC-1α knockout mice. These data suggest that skeletal muscle-PGC-1α is important for leucine-mediated mTOR activation and protein biosynthesis.