The impact of disuse and high-fat overfeeding on forearm muscle amino acid metabolism in humans

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Abstract

Context: Anabolic resistance is mechanistically implicated in muscle disuse atrophy. Objective: The objective of this study is to assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability. Design, Setting, Participants, and Interventions: Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n = 11) or high-fat overfeeding (HFD; n = 9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit. Main Outcome Measures: Preimmobilization and postimmobilization we measured forearm muscle cross-sectional area (aCSA), and postabsorptive and postprandial (3-hour postingestion of a liquid, protein-rich, mixed meal) forearm amino acid metabolism using the arterialized venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C] leucine. Results: Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P = .07) and leucine (P = .05) net balances equivalently in CON and HFD. Mixed-meal ingestion switched phenylalanine and leucine net balances from negative to positive (P < .05), an effect blunted by immobilization (P < .05) and to a greater extent in HFD than CON (P < .05). Preimmobilization, meal ingestion increased leucine rates of disappearance (Rd; P < .05), with values peaking at 191% (from 87 ± 38 to 254 ± 60 µmol·min–1·100 mL forearm volume–1) and 183% (from 141 ± 24 to 339 ± 51 µmol·min–1·100 mL–1) above postabsorptive rates in CON and HFD, respectively, with meal-induced increases not evident postimmobilization in either group (P > .05). Conclusions: Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.

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Wall, B. T., Cruz, A. M., Otten, B., Dunlop, M. V., Fulford, J., Porter, C., … Dirks, M. L. (2020). The impact of disuse and high-fat overfeeding on forearm muscle amino acid metabolism in humans. Journal of Clinical Endocrinology and Metabolism, 105(7). https://doi.org/10.1210/clinem/dgaa184

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