Resveratrol improves muscle regeneration in obese mice through enhancing mitochondrial biogenesis
Abstract
Obesity is increasing rapidly worldwide and is accompanied by many complications, including impaired muscle regeneration. Obesity is known to inhibit AMP-activated protein kinase (AMPK) activity, which impedes mitochondrial biogenesis, myogenic differentiation and muscle regeneration. Resveratrol has an effective anti-obesity effect, but its effect on regeneration of muscle in obese mice remains to be tested. We hypothesized that resveratrol activates AMPK and mitochondrial biogenesis to improve muscle regeneration. Male C57BL/6J mice were fed a control diet or a 60% high-fat diet with or without resveratrol supplementation for 8 weeks and, then, the tibialis anterior muscle was subjected to cardiotoxin-induced muscle injury. Muscle tissue was collected at 3 and 7 d after injury. We found that resveratrol enhanced both proliferation and differentiation of satellite cells following injury in obese mice. Markers of mitochondrial biogenesis were upregulated in resveratrol-treated mice. In C2C12 myogenic cells, resveratrol activated AMPK and stimulated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, which were associated with enhanced myogenic differentiation. Such effects of resveratrol were abolished by AMPKα1 ablation, showing the mediatory roles of AMPK. In summary, dietary resveratrol activates AMPK/ proliferator-activated receptor gamma coactivator 1-alpha axis to facilitate mitochondrial biogenesis and muscle regeneration impaired due to obesity.
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Resveratrol protects against obesity-induced impairments in mitochondrial biogenesis by stimulating the SIRT1/AMPK/PGC1α pathway.
“Notably, resveratrol, one of the well-known bioactive polyphenols and popular exercise mimetic, protects against obesity-induced impairments in mitochondrial biogenesis by stimulating SIRT1/AMPK/PGC1α pathway [57].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [57]
High-fat diet-induced obese mice exhibited decreased mtDNA content, expression of PGC1α, and several mitochondrial markers.
“High-fat diet-induced obese mice exhibited decreased mtDNA content, expression of PGC1α, and several mitochondrial markers.”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [57]
Mitochondrial biogenesis is critical for myogenic differentiation and muscle regeneration.
“Mitochondrial biogenesis is critical for myogenic differentiation and muscle regeneration [57].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [57]
Activation of AMPK increased the density of quiescent satellite cells, enhanced satellite cell proliferation, and promoted satellite cell myogenic differentiation in regenerating muscle.
“This was confirmed when activation of AMPK increased the density of quiescent satellite cells, enhanced satellite cell proliferation, and promoted satellite cell myogenic differentiation in regenerating muscle [57].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [57]
Obesity inhibits AMPK activity, negatively impacting PGC1α transcription and co-activator functions, thereby impairing mitochondrial biogenesis in skeletal muscle.
“Obesity inhibits AMPK activity, which negatively impacts PGC1α transcription and its co-activator functions, [57] thereby impairing mitochondrial biogenesis in skeletal muscle.”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [57]
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- Authors
- Niu, W., Wang, H., Wang, B., Mao, X., & Du, M.
- Affiliations
- China Agricultural University (CN)
- Southwest Minzu University (CN)
- State Key Laboratory of Animal Nutrition (CN)
- Washington State University (US)
- Corresponding author
- Du, Min
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 98
- Pages
- 108804
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W3175833626
- Cited by
- 39
- References
- 54
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 8
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- resveratrol, muscle regeneration, obesity, mitochondrial biogenesis, AMPK, PGC-1α, satellite cells, myogenesis, cardiotoxin-induced muscle injury, high-fat diet, AMPKα1, tibialis anterior
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Resveratrol, Animals, Antioxidants, Organelle Biogenesis, Cell Differentiation, Male, Mice, Inbred C57BL, Mice, Obese, Mitochondria, Muscle, Obesity, Regeneration, Muscle, Skeletal, Muscle Development, Mice, AMP-Activated Protein Kinases, Diet, High-Fat
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