The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans

Abstract

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.