Effect of dietary protein on translation initiation in rat skeletal muscle and liver

The effect of dietary protein on the initiation of mRNA translation was examined in rats starved for 18 h and then fed isocaloric diets containing either 20% protein (20P) or no added protein (OP). Feeding the 20P diet, but not the 0P diet, stimulated protein synthesis in skeletal muscle and liver by 38 and 41%, respectively. The stimulation was associated with reduced binding of eukaryotic initiation factor (eIF) 4E to the translational repressor 4E- BP1, increased formation of the active eIF4E-eIF4G complex, and increased phosphorylation of 4E-BP1. In contrast, feeding a 0P diet had no effect on any of these parameters. Feeding a 20P diet resulted in partial dephosphorylation of eIF4E in both tissues. In liver, refeeding a 0P diet also resulted in partial eIF4E dephosphorylation, suggesting that the phosphorylation state of eIF4E is not important in the stimulation of protein synthesis under these conditions. Finally, plasma insulin concentrations were the same in rats fed either diet (14.8 ± 4.9 vs. 15.5 ± 4.5 μU/ml for 20P and 0P groups, respectively), suggesting that feeding-induced changes in plasma insulin are not sufficient to stimulate protein synthesis. Instead, a combination of dietary protein and insulin may be required to stimulate translation initiation.