title: Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion.
abstract: Disuse leads to rapid loss of skeletal muscle mass and function. It has been hypothesized that short successive periods of muscle disuse throughout the lifespan play an important role in the development of sarcopenia. The physiological mechanisms underlying short-term muscle disuse atrophy remain to be elucidated. We assessed the impact of 5 days of muscle disuse on postabsorptive and postprandial myofibrillar protein synthesis rates in humans. Twelve healthy young (22 ± 1 yr) men underwent a 5-day period of one-legged knee immobilization (full leg cast). Quadriceps cross-sectional area (CSA) of both legs was assessed before and after immobilization. Continuous infusions of l-[ring-(2)H5]phenylalanine and l-[1-(13)C]leucine were combined with the ingestion of a 25-g bolus of intrinsically l-[1-(13)C]phenylalanine- and l-[1-(13)C]leucine-labeled dietary protein to assess myofibrillar muscle protein fractional synthetic rates in the immobilized and nonimmobilized control leg. Immobilization led to a 3.9 ± 0.6% decrease in quadriceps muscle CSA of the immobilized leg. Based on the l-[ring-(2)H5]phenylalanine tracer, immobilization reduced postabsorptive myofibrillar protein synthesis rates by 41 ± 13% (0.015 ± 0.002 vs. 0.032 ± 0.005%/h, P < 0.01) and postprandial myofibrillar protein synthesis rates by 53 ± 4% (0.020 ± 0.002 vs. 0.044 ± 0.003%/h, P < 0.01). Comparable results were found using the l-[1-(13)C]leucine tracer. Following protein ingestion, myofibrillar protein bound l-[1-(13)C]phenylalanine enrichments were 53 ± 18% lower in the immobilized compared with the control leg (0.007 ± 0.002 and 0.015 ± 0.002 mole% excess, respectively, P < 0.05). We conclude that 5 days of muscle disuse substantially lowers postabsorptive myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Wall
authors.affiliation: NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and.
authors.forename: Marlou L
authors.initials: ML
authors.lastname: Dirks
authors.affiliation: NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and.
authors.forename: Tim
authors.initials: T
authors.lastname: Snijders
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: van Dijk
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Fritsch
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and.
authors.forename: Lex B
authors.initials: LB
authors.lastname: Verdijk
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands; and l.vanloon@maastrichtuniversity.nl.
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
mesh_terms: D004044:Dietary Proteins / Q000378:metabolism*; D006801:Humans; D007103:Immobilization; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D052097:Quadriceps Muscle / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004044:Dietary Proteins
keywords: amino acids; immobilization; muscle atrophy; skeletal muscle