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

Mitchell, W. Kyle; Phillips, Bethan E.; Hill, Ian; Greenhaff, Paul L.; Lund, Jonathan N.; Williams, John P.; Rankin, Debbie; Wilkinson, Daniel J.; Smith, Kenneth; Atherton, Philip J.

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 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.

Citation

Mitchell, W. K., Phillips, B. E., Hill, I., Greenhaff, P. L., Lund, J. N., Williams, J. P., Rankin, D., Wilkinson, D. J., Smith, K., & Atherton, P. J. (2017). Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men. Clinical Science, 131(21), https://doi.org/10.1042/CS20171230

• Journal Article Type: Article
• Acceptance Date: Oct 4, 2017
• Publication Date: Oct 27, 2017
• Deposit Date: Nov 1, 2017
• Publicly Available Date: Nov 1, 2017
• Journal: Clinical Science
• Print ISSN: 0143-5221
• Electronic ISSN: 1470-8736
• Publisher: Portland Press
• Peer Reviewed: Peer Reviewed
• Volume: 131
• Issue: 21
• DOI: https://doi.org/10.1042/CS20171230
• Public URL: https://nottingham-repository.worktribe.com/output/889809
• Publisher URL: https://doi.org/10.1042/CS20171230
• Contract Date: Nov 1, 2017