Muscle Protein Synthesis Refractoriness is overcome by an Oral Leucine or Carbohydrate Supplement

Abstract

The molecular machinery responsible for postprandial stimulation of muscle protein synthesis (MPS) becomes refractory to prolonged elevation of plasma amino acids or leucine (Leu). This study evaluates the potential of nutritional supplements to prolong MPS after a meal. Rats were food deprived for 13 h, then control rats (n=6 per group) were sacrificed at time 0 (fasted) and at 90 min (peak MPS) or 180 min (refractory period) after a standard 4 g meal containing 20% whey protein. Treatment groups received an oral gavage of a sham control (water), 2.63 g carbohydrate (50% glucose and sucrose), 270 mg Leu, or 2.35 g of carbohydrate and 270 mg Leu at 145 min post-meal and were sacrificed at 180 min. MPS peaked at 90 min, declined to fasted values at 180 min (sham). All three treatments sustained MPS at 180 min. An inverse correlation was found between MPS and AMPKα phosphorylation (activation) (r=−0.581; p<.05); from 90–180 min (refractory period) there was a positive correlation between AMPKα phosphorylation and eEF2 phosphorylation (inhibition) (r=0.495; p<.05), while MPS from 90–180 min did not correlate with either p70S6K1 phosphorylation (activation) or plasma insulin. These data suggest that the refractory period is related to inhibitory effects of AMPK on translation elongation, rather than translation initiation.