doi:10.1210/clinem/dgaa184 J Clin Endocrinol Metab, July 2020, 105(7):e2547–e2562 https://academic.oup.com/jcem e2547 CLINICAL RESEARCH ARTICLE The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans Benjamin T. Wall, 1 Ana M. Cruz, 1,2 Britt Otten, 1 Mandy V. Dunlop, 1 Jonathan Fulford, 2 Craig Porter, 3 Doaa Reda Abdelrahman, 3 Francis B. Stephens, 1 and Marlou L. Dirks 1 1 Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, UK; 2 Exeter Medical School, University of Exeter, UK; and 3 Department of Surgery, University of Texas Medical Branch & Metabolism Unit, Shriners Hospital for Children, Galveston, 77550-1220, USA ORCiD numbers: 0000-0002-6019-6709 (B. T. Wall); 0000-0002-9189-1042 (M. L. Dirks). 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- 2 H 5 ]phenylalanine and L-[1- 13 C] 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 (R d ; 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. (J Clin Endocrinol Metab 105: e2547–e2562, 2020) Key Words: disuse, arteriovenous balance, skeletal muscle, amino acid uptake, stable isotopes, anabolic resistance, atrophy Abbreviations: aCSA, anatomical cross-sectional area; AV-V, arterialized venous–deep venous; CON, eucaloric; GC-MS, gas chromatography–mass spectrometry; HFD, high- fat overfeeding; MPB, muscle protein breakdown; MPE, mole percent excess; MPS, muscle protein synthesis; MRI, magnetic resonance imaging. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals. permissions@oup.com Received 11 February 2020. Accepted 16 April 2020. First Published Online 18 April 2020. Corrected and Typeset 6 May 2020. Downloaded from https://academic.oup.com/jcem/article/105/7/e2547/5821526 by guest on 20 June 2022