Regulation of leucyl‐tRNA synthetase and RagB expression in human skeletal muscle by essential amino acids (1161.4)

Abstract

Essential amino acids (EAA) are a potent stimulator of mammalian target of rapamycin (mTORC1) signaling and protein synthesis. However, the molecular regulators upstream of mTORC1 signaling that are stimulated by EAA are not well described especially in human skeletal muscle. Leucyl tRNA Synthetase (LRS) and RagB have recently been shown to be important in mTORC1 activation. The purpose of this study was to determine if the LRS‐ and RagB‐mTORC1 complexes and LRS and RagB gene and protein expression are altered following acute EAA ingestion in healthy human skeletal muscle. Muscle biopsies (vastus lateralis) were obtained from 8 young adults (4M, 4F) in the fasted state (basal) and 1 and 3h after EAA (13g; 2.4g Leu) ingestion. Co‐immunoprecipates were used to determine LRS‐ and RagB‐mTORC1 protein complexes and whole muscle homogenates were analyzed for LRS and RagB gene and protein expression and mTOR phosphorylation. We found that EAA increased RagB protein abundance and mTOR phosphorylation 1h following EAA ingestion (P<0.05). However EAA ingestion did not alter LRS‐ or RagB‐mTORC1 complexes, LRS protein expression or change LRS and RagB gene expression 1 or 3h‐post EAA. We conclude that LRS‐ and RagB‐mTORC1 complexes are not altered 1 and 3h‐post EAA. However, RagB protein increased after EAA ingestion in healthy human skeletal muscle, which may be a mechanism to promote protein anabolism.Grant Funding Source: Supported by K01 AG038556 and UL1 TR000105