Atrophy, Disuse, Disuse Atrophy, Disuse Atrophy Muscle of Thigh, Muscle Atrophy, Muscular Disorders, Atrophic
Conditions
Brief summary
This study will characterize intramuscular molecular mechanisms underlying anabolic resistance to protein ingestion during muscle disuse. Adults (n=12) will be studied using a unilateral leg immobilization model in which one leg will be randomly assigned to immobilization and the contralateral, active leg used as a within-subjects control. Immobilization will be implemented for five days using a rigid knee brace, during which time participants will ambulate using crutches. Integrated ribonucleic acid (RNA) synthesis will be determined during immobilization in the immobilized and non-immobilized legs using ingested deuterium oxide, salivary and blood sampling, and muscle biopsies. Immediately after immobilization, muscle biopsies will be collected before and 90 mins after consuming 25 g of whey protein from the immobilized and non-immobilized legs to characterize the intramuscular molecular response to protein feeding. Serial blood samples will be collected during that time to characterize the circulating metabolic response to protein ingestion. Knowledge generated from this effort will inform the development of targeted interventions for mitigating anabolic resistance to protein ingestion that develops during periods of muscle disuse.
Detailed description
Warfighters that sustain musculoskeletal injuries often experience decreased muscle loading and activation post-injury (i.e., muscle disuse) that results in a rapid loss of muscle mass and function. Loss of muscle under these conditions is attributed to a persistent negative net muscle protein balance (muscle protein synthesis \[MPS\] \< muscle protein breakdown \[MPB\]) that results, in part, from a blunting of MPS in the postprandial state. Nutritional interventions that optimize postprandial MPS have been suggested as countermeasures for this anabolic resistance that develops during disuse to preserve muscle mass and accelerate return to duty. However, a poor understanding of mechanisms underlying anabolic resistance during disuse has made it difficult to determine an optimal nutritional intervention. The current study will address this knowledge gap directly by characterizing intramuscular molecular mechanisms underlying anabolic resistance to protein ingestion during muscle disuse. Healthy, recreationally active men and women (n=12) will be studied using a within-subjects, unilateral design. After completing baseline measures of height, weight, and body composition, participants will begin a 3-day run-in phase where they will receive diet instructions (no food provided). Muscle disuse will then be implemented for 5 days using a unilateral leg immobilization model with one leg randomly assigned to immobilization and the contralateral, active leg used as a within-subjects control. Immobilization will be implemented using a rigid knee brace, and participants will ambulate using crutches. Diets will be standardized during the immobilization phase (1.0 g protein/kg/d, 30% of energy intake from fat, and the remaining calories from carbohydrate). Integrated ribonucleic acid (RNA) synthesis will be determined during immobilization in the immobilized and non-immobilized legs using ingested deuterium oxide, salivary and blood sampling, and muscle biopsies. Immediately after immobilization, muscle biopsies will be collected before and 90 mins after consuming 25 g of whey protein from the immobilized and non-immobilized legs to characterize the intramuscular molecular response to protein feeding. Serial blood samples will be collected during that time to characterize the circulating metabolic response to protein ingestion. Knowledge generated from this effort will inform the development of targeted interventions for mitigating anabolic resistance to protein ingestion that develops during periods of muscle disuse.
Interventions
OTHERUnilateral leg immobilization
Participants will have one leg immobilized using a rigid knee brace. Participants will be expected to keep the knee brace on for 5 days and remain non-weight bearing on the immobilized leg. Participants will use crutches to remain non-weight bearing on the immobilized leg.
OTHERContralateral active leg
One leg will remain non-immobilized and active during the study. Participants will use this leg to walk with crutches.
Sponsors
United States Army Research Institute of Environmental Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Single leg immobilization model consisting of one leg randomly assigned to immobilization with a knee brace and the other leg remaining active and non-immobilized, for 5 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women aged 18-39 years. * Body mass index (BMI) between 18.5-30 kg/m2 * Healthy without evidence of chronic illness (e.g., diabetes, cardiovascular disease, Crohn's disease) or musculoskeletal injury as determined by the USARIEM Office of Medical Oversight (OMSO) or home duty station medical support. * Routinely participate in aerobic and/or resistance exercise at least 2 days per week. * Willing to refrain from alcohol, smoking, smokeless nicotine products (includes e-cigarettes, vaping, chewing tobacco), caffeine, and dietary supplements (i.e., vitamin D, probiotics) during the run-in diet, immobilization phase, and final testing day of the study. * Supervisor approval for federal civilian employees and non-human research volunteer (HRV) active-duty military personnel stationed at Natick Soldier System Center (NSSC). * Biological females must have normal menstrual cycles between 26-32 days in duration; 5 menstrual cycles within the past 6 months; or on continuous hormonal contraception (i.e., intrauteraine device (IUD) or oral contraceptives without placebo).
Exclusion criteria
* Musculoskeletal injuries that may interfere with the safe use of crutches. * Personal or family history of thrombosis, or prior diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE). * Metabolic or cardiovascular abnormalities, gastrointestinal disorders, neuromuscular disorders, lower-limb amputation, or muscle/bone wasting disorders (e.g., diabetes, cardiovascular disease, Crohn's disease, etc.). * Significantly abnormal blood clotting as determined by OMSO or home duty station medical support. * Allergy to lidocaine (or similar local anesthetic) * Present condition of alcoholism, anabolic steroid use, or other substance abuse issues as determined by OMSO or home duty station medical support. * Blood donation within 8-wk of beginning the study. * Pregnant, trying to become pregnant, and/or breastfeeding (results of urine pregnancy test and self-report for breastfeeding will be obtained before body composition testing). * Unwilling or unable to consume study diets or foods provided due to personal preference and/or food allergies. * Unwilling or unable to adhere to study physical restrictions (i.e., no structured physical activity or recreational activity beyond activities of daily living) 24 hours before and during immobilization, and the final testing day. * Unwilling or unable to keep the knee brace on and walk with crutches during the immobilization phase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Integrated ribonucleic acid (RNA) synthesis | 5 days | deuterium oxide coupled with muscle biopsies |
| Intramuscular protein signaling response to protein ingestion | 90 minutes | muscle biopsies to assess protein signaling response to consuming 25 g of whey protein |
Countries
United States
Outcome results
None listed