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Leucine partially protects muscle mass and function during bed rest in middle-aged adults.

ABSTRACT: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults.The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest.We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ? kg(-1) ? meal(-1)) or an alanine control (CON group) during 14 d of bed rest.Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05).Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.

SUBMITTER: English KL

PROVIDER: S-EPMC4733256 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Leucine partially protects muscle mass and function during bed rest in middle-aged adults.

English Kirk L KL Mettler Joni A JA Ellison Jennifer B JB Mamerow Madonna M MM Arentson-Lantz Emily E Pattarini James M JM Ploutz-Snyder Robert R Sheffield-Moore Melinda M Paddon-Jones Douglas D

The American journal of clinical nutrition 20151230 2

<h4>Background</h4>Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults.<h4>Objective</h4>The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest.<h4>Design</h4>We used a randomized, double-blind, placebo-controlled trial to asse ...[more]

PMID: 26718415

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Project description:Short-term bed rest in older adults is characterized by significant loss in leg lean mass and strength posing significant health consequences. The purpose of this study was to determine in healthy older adults if the daily combination of neuromuscular electrical stimulation and protein supplementation (NMES+PRO) would protect muscle mass and function after 5 days of bed rest. Twenty healthy older adults (?70 years) were subjected to 5 days of continuous bed rest and were randomized into one of two groups: NMES+PRO (n?=?10) or control (CON) (n?=?10). The NMES+PRO group received bilateral NMES to quadriceps (40 minutes/session, 3?×?/day; morning, afternoon, and evening) followed by an interventional protein supplement (17?g). The CON group received an isocaloric equivalent beverage. Before and after bed rest, vastus lateralis biopsies occurred before and after acute essential amino acid (EAA) ingestion for purposes of acutely stimulating mechanistic target of rapamycin (mTORC1) signaling, a major regulator of muscle protein synthesis, in response to bed rest and NMES+PRO. Baseline (pre and post bed rest) muscle samples were also used to assess myofiber characteristics and gene expression of muscle atrophy markers. Thigh lean mass and muscle function were measured before and after bed rest. Five days of bed rest reduced thigh lean mass, muscle function, myofiber cross-sectional area, satellite cell content, blunted EAA-induced mTORC1 signaling, and increased myostatin and MAFbx mRNA expression. Interestingly, NMES+PRO during bed rest maintained thigh lean mass, but not muscle function. Thigh muscle preservation during bed rest with NMES+PRO may partly be explained by attenuation of myostatin and MAFbx mRNA expression rather than restoration of nutrient-induced mTORC1 signaling. We conclude that the combination of NMES and protein supplementation thrice a day may be an effective therapeutic tool to use to preserve thigh muscle mass during periods of short-term hospitalization in older adults. However this combined intervention was not effective to prevent the loss in muscle function.

Project description:Microgravity has a dramatic impact on human physiology, illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for the definition of efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n=8), and the potential beneficial impact of protein supplementation (BRN group, n=8) and of a combined resistance and aerobic training (BRE group, n=8). Gene expression profiles were obtained using an in-house made microarray containing 6681 muscles-relevant genes. A two-class statistical analysis was applied on the 2103 genes with consolidated expression. We identified 472 and 207 modified genes, respectively for SOL and VL in BRC group. Further clustering approaches, identifying relevant biological mechanisms or pathways, underlined five main subclusters. Three are composed almost of upregulated genes involved mainly in nucleic acid and protein metabolism, and two composed almost of downregulated genes involved in energy metabolism. Exercise countermeasure demonstrated a drastic compensatory effect, decreasing the number of differentially-expressed genes by 89 and 96% in SOL and VL. In contrast, nutrition countermeasure had a moderate effect and decreased the number of differentially-expressed genes by 40 and 25% in SOL and VL. Our results allowed reporting a systematic, global and comprehensive view of long-term woman muscle atrophy and brought new lights and insights for space environment and for women who undergo a long-term clinical bed rest. Biological samples were collected from Pre- and Post- bed rest (BR) soleus and vastus lateralis biopsies of each subject from the three groups (bed rest only: BRC; Exercise: BRE; Nutrition: BRN). six technical replicate values (2 duplicate hybridizations âa et bâ to chips with triplicate spots âxxxâ) were obtained for each skeletal muscle sample. Thus for each subject, 12 expression measurements (6 before BR and 6 after BR) were obtained for each muscle.

Project description:Short-term muscle disuse induces significant muscle loss in older adults and in some reports may be more accelerated with aging. Identifying muscle transcriptional events in response to bed rest may help identify therapeutic targets to offset muscle loss. Therefore, we compared the muscle transcriptome between young and older adults after bed rest and identified candidate targets related to changes in muscle loss. RNA was sequenced (HiSeq, Illumina; DESeq, R) from muscle biopsies obtained from young [ n = 9; 23 yr (SD 3)] and older [ n = 18; 68 yr (SD 6)] adults before and after 5-day bed rest. Significantly altered pathways in both young and old subjects relating to mechanosensing and cell adhesion (Actin Cytoskeleton Signaling, ILK Signaling, RhoA Signaling, and Integrin Signaling) were altered (activation z score) to a greater extent in old subjects. Hepatic Fibrosis/Hepatic Stellate Cell Activation was the top regulated pathway significantly altered only in the old. Fifty-one differentially regulated genes were only altered in the young after bed rest and resembled a gene expression profile like that in the old at baseline. Inflammation and muscle wasting genes (CXCL2, GADD45A) were uniquely increased in the old after bed rest, and the macrophage gene MAFB decreased in the old and correlated with the change in leg lean mass. In summary, skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aid in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. NEW & NOTEWORTHY Using RNA sequencing and bioinformatics approaches, we identified that older adult skeletal muscle was characterized by dysregulated pathways associated with fibrosis, inflammation (upregulated), and cell adhesion and mechanosensing (downregulated) pathways, with a subset of genes differentially regulated in old and young muscle after bed rest that may describe predisposition to muscle loss. Unique upregulated genes only expressed in old muscle after bed rest indicated increased inflammation and muscle wasting (CXCL2, GADD45A) and decreased MAFB correlated with the change in leg lean mass.

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Leucine partially protects muscle mass and function during bed rest in middle-aged adults.

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Leucine partially protects muscle mass and function during bed rest in middle-aged adults.

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