Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle
Open accessAbstract
BACKGROUND: The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. PRINCIPAL FINDINGS: Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups. CONCLUSIONS: These findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties.
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Muscle β-oxidation increases in response to a high-fat diet, but excessive lipid content or duration can exceed this capacity, leading to ectopic lipid accumulation and impaired lipid metabolism.
“muscle β-oxidation increases in response to a high-fat diet (HFD) [83–86], although excessive lipid content or duration of such diets can exceed this capacity, leading to ectopic lipid accumulation and impaired lipid metabolism [87–91].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [90]
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- Authors
- Shortreed, K. E., Krause, M. P., Huang, J. H., Dhanani, D., Moradi, J., Ceddia, R. B., & Hawke, T. J.
- Affiliations
- York University (CA)
- Corresponding author
- Hawke, Thomas J.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-10-06
- Volume
- 4
- Issue
- 10
- Pages
- e7293
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2752162
- OpenAlex
- W2116618150
- Cited by
- 131
- References
- 29
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 15 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 6 · 2015: 12 · 2014: 13 · 2013: 11 · 2012: 4
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ontario Innovation Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- diet-induced obesity, high-fat diet, skeletal muscle, oxidative metabolism, muscle fiber type, intramyocellular lipid, palmitate oxidation, glucose oxidation, succinate dehydrogenase, citrate synthase, muscle contractility, insulin resistance, prediabetes, gastrocnemius, soleus muscle, tibialis anterior, extensor digitorum longus
- MeSH terms
- Animals, Animal Feed, Blood Glucose, Dietary Fats, Glucose, Lipids, Male, Mice, Inbred C57BL, Muscle Contraction, Obesity, Oxygen, Time Factors, Muscle, Skeletal, Mice, Animal Nutrition Sciences
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