# Voluntary Exercise-Induced Skeletal Muscle Responses in Young and Aged Mice on a High-Fat Diet

**Authors:** Yuji Kanazawa, Kenichiro Miyahara, Tatsuo Takahashi, Ryo Miyachi, Takashi Higuchi, Takaaki Nishimura, Hiaki Sato, Yuri Ikeda-Matsuo

PMC · DOI: 10.7759/cureus.86697 · Cureus · 2025-06-24

## TL;DR

Voluntary exercise helps reduce body weight and boost muscle metabolism in mice on a high-fat diet, but its effects on fat accumulation depend on age and muscle type.

## Contribution

Shows voluntary exercise improves mitochondrial activity in aged mice on high-fat diets, despite limited fat reduction in certain muscles.

## Key findings

- Voluntary exercise reduced body weight in both young and aged mice on a high-fat diet.
- Exercise increased mitochondrial activity in gastrocnemius muscles but not intramuscular fat in aged mice.
- Soleus muscle showed minimal response to exercise in both age groups.

## Abstract

Background and objective

Aging and consumption of a high-fat diet (HFD) are associated with increased body weight and reduced skeletal muscle quality. Although aerobic exercise is generally considered protective against these risks, the impact of self-initiated physical activity on an HFD in older individuals remains unclear. This study aimed to investigate the influence of spontaneous wheel-running on body weight, intramuscular fat accumulation, and mitochondrial metabolic function in the skeletal muscles of young and aged mice on HFD.

Methods

Male C57BL/6J mice aged 14 weeks (young group) and 84 weeks (aged group) were assigned to either exercise or sedentary groups and fed an HFD for eight weeks. Measurements included body weight, muscle weight (gastrocnemius and soleus), muscle fiber cross-sectional area (FCSA), succinate dehydrogenase (SDH) activity, and intramuscular fat area via Oil Red O staining.

Results

Voluntary exercise significantly reduced the body weight in both age groups. While the muscle weight and FCSA remained unchanged by exercise, exercise led to elevated SDH activity in the gastrocnemius muscles of both young and aged mice, suggesting increased mitochondrial metabolic activity. Exercise increased intramuscular fat content in the gastrocnemius muscle of young mice, but not in aged mice. The soleus muscle showed a minimal response to both metabolic activity and fat accumulation by exercise, regardless of age.

Conclusions

Voluntary wheel running under HFD conditions effectively lowered body weight and increased mitochondrial activity in gastrocnemius muscle fibers. However, intramuscular fat responses vary according to muscle type and age, suggesting that aging diminishes skeletal muscle adaptability to exercise in the context of lipid metabolism.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Aass (aminoadipate-semialdehyde synthase) [NCBI Gene 30956] {aka LKR, LKR/SDH, LOR, LOR/SDH, Lorsdh, SDH}
- **Chemicals:** Fat (MESH:D005223), lipid (MESH:D008055), Oil Red O (MESH:C011049)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12290238/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12290238/full.md

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Source: https://tomesphere.com/paper/PMC12290238