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

Clin Sci (Lond). 2017 Oct 27;131(21):2643-2653. doi: 10.1042/CS20171230. Print 2017 Nov 1.

Abstract

Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that 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 (∼70 years) consumed 15 g of EAA with (n=8, FED + LEU) or without (n=8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml-1 25 min post-feed), essential aminoacidemia (3000 μM, 45-65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 μM, 135 min) and leucine availability (1050 μM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h-1 (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h-1 90-180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle high-energy phosphates, but did induce eukaryotic elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition.

Keywords: amino acid metabolism; mechanistic target of rapamycin; nutrition; protein synthesis; skeletal muscle.

Publication types

  • Clinical Trial

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Age Factors
  • Aged
  • Aging / blood
  • Aging / metabolism*
  • Anabolic Agents / administration & dosage*
  • Anabolic Agents / blood
  • Dietary Supplements*
  • Energy Metabolism / drug effects*
  • Humans
  • Insulin / blood
  • Leucine / administration & dosage*
  • Leucine / blood
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phosphocreatine / metabolism
  • Phosphorylation
  • Postprandial Period*
  • Prospective Studies
  • Protein Biosynthesis / drug effects*
  • Sex Factors
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors

Substances

  • Anabolic Agents
  • Insulin
  • Multiprotein Complexes
  • Phosphocreatine
  • Adenosine Triphosphate
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Leucine