Transcriptome-wide RNA sequencing analysis of immobilisation-induced muscle atrophy

Kevin John Ashton, J. M. Thompson, Boris P Budiono, Katsuhiko Shike, Kristen MacKenzie, Thomas M Doering, Vernon G Coffey

Research output: Contribution to conferenceAbstractResearchpeer-review

Abstract

INTRODUCTION: Disuse atrophy is a secondary complication that often
xacerbates the aetiology of injury and chronic disease. Identifying the mechanisms that control muscle mass associated with changes in function is necessary to characterize atrophy and better understand the effects of disuse on skeletal muscle. RNA sequencing was used as a high resolution, untargeted approach to study gene expression in human skeletal muscle following short-term limb immobilisation.

METHODS:
Twenty-one healthy male participants (aged 20-45 years) completed 4 weeks of standardized physical activity prior to a 14- day limb (left leg) immobilisation period. Participants also underwent 21 days (7 days prior; 14 days during immobilisation) of dietary control. Skeletal muscle biopsies were collected from the m. vastus lateralis before and after 3 and 14 days of immobilisation. Skeletal muscle RNA was isolated and analysed using Illumina RNA next generation sequencing to determine differential gene expression with
subsequent GO term/pathway analysis. Strength testing, DEXA and MRIs were also performed pre- and post-immobilisation to determine changes in muscle mass and function.
RESULTS: Following 14 days of limb immobilization, strength (-16.4%), leg lean mass (-3.2%) and quadricep cross-sectional area (-8.5%) were all significantly reduced. RNA sequencing identified significant changes in mitochondrial processes and carbohydrate metabolism which became more pronounced throughout the immobilisation period. Furthermore, changes in transcription regulation and chromatin remodelling processes occurred during the early unloading phase at 3 days, but not later at the end of 14 days. Conversely, changes in protein localisation, ribosome biogenesis, translation, nucleotide metabolism and oxidoreductase activity were identified after 14 days of
immobilisation but were unchanged at 3 days.
CONCLUSION: This study provides the first transcriptomic sequencing of short-term disuse atrophy in human skeletal muscle. These data provide further support for changes in gene expression related to mitochondrial dysfunction and reduced protein synthesis as key events. Interestingly, changes in transcription regulation including chromatin remodelling processes were observed as an early event and may be responsible for modifying later transcriptomic responses to short-term disuse atrophy.
Original languageEnglish
Pages577
Publication statusPublished - Jul 2018
Event23rd Annual Congress of the European College of Sport Science - Dublin, Ireland
Duration: 4 Jul 20187 Jul 2018
Conference number: 23
http://ecss-congress.eu/2018

Conference

Conference23rd Annual Congress of the European College of Sport Science
Abbreviated titleECSS
CountryIreland
CityDublin
Period4/07/187/07/18
Internet address

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