Chronic Enteral Leucine Supplementation of a Low Protein Diet Increases Skeletal Muscle Protein Synthesis in Neonatal Pigs by Stimulating mTOR‐Dependent Translation Initiation

Abstract

Leucine appears to be the key amino acid that positively regulates mTOR signalling. We hypothesized that prolonged feeding (24 hours) of a Leu supplemented low protein (LP) diet in neonatal pigs will increase protein synthesis in skeletal muscle to a rate similar to that of a high protein diet (HP). Fasted 5‐d‐old piglets (n=17) were gavage fed every 4 hours either: 1) LP diet, 2) low protein diet supplemented with Leu (LP+L) to equal HP diet, or 3) HP diet. Diets were isocaloric and lactose was equal. Fractional protein synthesis rates and translational control mechanisms were examined after 24 hours. Protein synthesis increased in the skeletal muscle of the LP+L group compared to LP group alone and did not differ from HP group. LP+L and HP increased the phosphorylation of S6K1 and 4E‐BP1, decreased inactive 4E‐BP1 eIF4E complex abundance, and increased active eIF4E eIF4G complex formation in skeletal muscle. Our results suggest that chronic feeding of a low protein diet supplemented with leucine stimulates and maintains the protein synthesis response in skeletal muscle to a rate similar to that achieved by feeding a high protein diet and this stimulation involves increased eIF4F complex assembly. (Supported by Ajinomoto Amino Acid Research Program and USDA 58‐6250‐6‐001).Grant Funding Source: Ajinomoto Amino Acid Research Program and USDA 58‐6250‐6‐001