Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men

Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS and muscle energy metabolism in older men. During 13C6-phenylalanine infusion 16 men (~70y) consumed 15g EAA with (n=8, FED+LEU ) or without (n=8, FED ) 3g leucine top-up 90min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTORc1 substrates, cellular ATP and phosphorylocreatine and MPS. Oral EAA achieved rapid insulinaemia (12.5iU.ml-1 25 min post-feed), essential aminoacidemia (3000 mM, 45-65 min post-feed), and activation of mTORC1-signaling. Leucine top-up prolonged plasma EAA (2800mM, 135 min) and leucine availability (1050mM, 135min post-feed). Fasting FSR's of 0.046 and 0.056%.h-1 ( FED and FED+LEU respectively) increased to 0.085 and 0.085%.h-1 90-180min post-feed and returned to basal rates after 180min in both groups. Phosphorylation of mTORc1-substrates returned to fasting levels 240min post-feed in both groups. Feeding had limited effect on muscle high-energy phosphates, but did induce eukaryotic elo...

Source: Clinical Science - October 5, 2017 Category: Biomedical Science Authors: Mitchell, W. K., Phillips, B. E., Hill, I., Greenhaff, P., Lund, J. N., Williams, J. P., Rankin, D., Wilkinson, D. J., Smith, K., Atherton, P. J. Tags: PublishAheadOfPrint Source Type: research