The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles
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Prolonged high-fat diets (HFD) can cause intramyocellular lipids (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether effects are muscle-specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles from female CD-1 mice divided into 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-CON, n=28). The young animals were 20 weeks old at the end of the experiment. Sixty 70-week-old female CD-1 mice received either a normal diet (O-CON, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and IMCL content increased in old OS-HFD (p≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (p≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger compared to Y-CON (p≤0.004) while old mice had a larger soleus FCSA compared to CON after only 9 weeks on a HFD (p<0.001). The FCSA of the EDL muscle did not differ significantly between groups. Oxidative capacity of fibres increased in young only, irrespective of HFD duration (p<0.001). High-fat diet-induced morphological changes occur earlier in the old animals when compared to young, and adaptations to HFD are muscle-specific with the EDL being least responsive.
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Impaired metabolic flexibility with regard to both supply and demand perturbations has been reported in old age.
“Impaired metabolic flexibility with regard to both supply and demand perturbations has been reported in old age [65, 80, 89, 92]”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [89]
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 [89]
Pre-clinical studies indicate that adipose tissue damages muscle homeostasis, resulting in muscle atrophy and reduced regeneration capacity, regarded as the pathogenic mechanism of sarcopenic obesity.
“There has been evidence from pre-clinical studies indicating that adipose tissue damages muscle homeostasis, resulting in muscle atrophy and regeneration capacity reduction (16, 17). This finding was regarded as the pathogenic mechanism of sarcopenic obesity (17).”
From The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity (2023) · cites this paper as [16]
Pre-clinical studies reported that obesity impaired muscle glucose tolerance, imbalanced protein synthesis and degradation, and oxidative stress which ultimately led to muscle atrophy, especially in old animals.
“On the contrary, pre-clinical studies reported that obesity impaired muscle glucose tolerance, imbalanced protein synthesis and degradation, and oxidative stress which ultimately led to muscle atrophy, especially in old animals (16, 17).”
From The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity (2023) · cites this paper as [16]
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- Authors
- Messa, G. A. M., Piasecki, M., Hurst, J., Hill, C., Tallis, J., & Degens, H.
- Affiliations
- Manchester Metropolitan University (GB)
- University of Nottingham (GB)
- Coventry University (GB)
- King's College London (GB)
- Corresponding author
- Degens, H.
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2020-01-01
- Volume
- 223
- Issue
- Pt 6
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- PMC
- PMC7097303
- OpenAlex
- W3001468335
- Cited by
- 63
- References
- 82
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 1
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Experimental Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- e-space (Manchester Metropolitan University) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Pure (Coventry University) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Higher Education Funding Council for England
- Manchester Metropolitan University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- high-fat diet, intramyocellular lipid, muscle lipid accumulation, muscle aging, muscle fiber cross-sectional area, soleus muscle, extensor digitorum longus, diaphragm, oxidative capacity, muscle morphology, age-dependent effects, ICR mice
- MeSH terms
- Animals, Female, Lipids, Muscle, Skeletal, Mice, Diet, High-Fat
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