Cited by 67Sirtuins and Resveratrol in MedicineMuscle Physiology and DisordersAdipose Tissue and Metabolism

Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3

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Lin, Ligen, Chen, Keyun, Khalek, Waed Abdel, Ward, Jack Lee, Yang, Henry, Chabi, Béatrice, Wrutniak-Cabello, Chantal, Tong, Qiang·2014·PLoS ONE

Abstract

We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER), indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.

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Authors
Lin, L., Chen, K., Khalek, W. A., Ward, J. L., Yang, H., Chabi, B., Wrutniak-Cabello, C., & Tong, Q.
Affiliations
  • Baylor College of Medicine (US)
  • Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
Corresponding author
Tong, Qiang
Venue
PLoS ONE
Published
2014-01-15
Volume
9
Issue
1
Pages
e85636
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2044275161
Cited by
67
References
71
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 9 · 2020: 1 · 2019: 5 · 2018: 9 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 1
FWCI
2.38
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Department of Agriculture (6250-51000-055, 6250‐51000)
  • American Heart Association
  • National Institutes of Health
  • Agricultural Research Service (6250‐51000‐055, 6250-51000)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK56338, DK075978, P30DK079638, R01DK075978, P30DK056338)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
SIRT3, skeletal muscle, muscle mass, muscle atrophy, MuRF1, FOXO1, AMPK, PPARδ, energy expenditure, lipid oxidation, exercise performance, caloric restriction, mitochondrial deacetylase, transgenic mice
MeSH terms
Forkhead Box Protein O1, Animals, Citrate (si)-Synthase, Physical Exertion, Female, Male, Mice, Transgenic, Mitochondria, Muscle, Oxidation-Reduction, Oxygen Consumption, Up-Regulation, Muscle, Skeletal, Lipid Metabolism, Mice, Forkhead Transcription Factors, Creatine Kinase, MM Form, Muscle Strength, Sirtuin 3

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