Abstract
The acute increase of protein synthesis in response to food intake is achieved in part through increases in the rate of translation of mRNA by stimulating peptide-chain initiation. The increase of translation initiation in both skeletal muscle and liver in response to food intake was not associated with any detectable change in the activity of eIF2B or in the phosphorylation state of eIF2α, both of which regulate binding of the initiator methionyl-tRNAi to the 40S ribosomal subunit. Food intake stimulated translation initiation partly through enhanced association of eIF4G with eIF4E, an event that promotes binding of mRNA to the 40S ribosomal subunit. Furthermore, this study provided evidence that the protein component of the diet (i.e., amino acids) plays an important regulatory role in the initiation of mRNA translation. Of all the amino acids, leucine appears to be the most effective in recapitulating the responses of protein synthesis and the eIF4F regulatory step produced by ingestion of a protein-containing meal. Leucine-dependent stimulation of translation initiation in vivo occurs via a rapamycin-sensitive pathway and likely involves mTOR. In addition, leucine selectively enhances the translation of mRNAs encoding ribosomal proteins in association with the S6K1 signaling pathway in the liver.
