Early Mitochondrial Adaptations in Skeletal Muscle to Obesity and Obesity Resistance Differentially Regulated by High-Fat Diet
Abstract
The mechanism for different susceptibilities to obesity after short-term high-fat diet (HFD) feeding is largely unknown. Given the close association between obesity occurrence and mitochondrial dysfunction, the early events in skeletal muscle mitochondrial adaptations between HFD-induced obesity (DIO) and HFD-induced obesity resistant (DIO-R) lean phenotype under excess nutritional environment were explored. ICR/JCL male mice were randomly divided into 2 groups, as follows: low-fat diet (LFD) and HFD groups. After 6 weeks on HFD, HFD-fed mice were classified as DIO or DIO-R according to their body weight gain. Serum parameters, oxidative stress biomarkers, the activation of AMPK/ACC axis, and the expression profiles of mitochondrial biogenesis were measured by using corresponding methods among the LFD control, DIO, and DIO-R groups. Serum glucose, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels were significantly increased in DIO and DIO-R mice compared with LFD controls. However, DIO-R mice had significantly higher MDA levels and exhibited a significantly higher level of AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase (ACC) inactivation than DIO mice. Furthermore, the transcript and protein levels of transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) and estrogen-related receptor-α (ERRα) in DIO-R mice were significantly up-regulated compared with the DIO mice. Although the body weight gain differed, the DIO and DIO-R mice had similar metabolic disturbance of glucose and lipids after short-term HFD consumption. The diverse alterations on fatty acid oxidation and mitochondrial biogenesis pathway induced by AMPK activation might be involved in different susceptibilities to obesity when consuming HFD.
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An obesity-resistant lean phenotype tends to have higher expression of mitochondrial biogenesis markers, indicating a potential relationship between skeletal muscle mitochondrial biogenesis and the onset of obesity and obesity-resistance during high-fat diet feeding.
“Notably, obesity-resistant lean phenotype tends to have a higher expression of mitochondrial biogenesis markers, indicating potential relationship between mitochondrial biogenesis in skeletal muscle and the onset of obesity and obesity-resistance development in the course of high-fat diet feeding [56].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [56]
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- Authors
- Sun, J., Huang, T., Qi, Z., You, S., Dong, J., Zhang, C., Qin, L., Zhou, Y., & Ding, S.
- Affiliations
- Tongji University (CN)
- Shanghai Jiao Tong University (CN)
- East China Normal University (CN)
- Corresponding author
- Ding, Shuzhe
- ORCID
- Venue
- Experimental and Clinical Endocrinology & Diabetes
- Publisher
- Georg Thieme Verlag KG
- Published
- 2017-04-25
- Volume
- 125
- Issue
- 08
- Pages
- 538-546
- ISSN
- 0947-7349 (ISSN-L)
- 1439-3646
- OpenAlex
- W2608556478
- Cited by
- 12
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Clinical Endocrinology & Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Tongji University
- SLAC National Accelerator Laboratory
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- obesity susceptibility, obesity resistance, high-fat diet, skeletal muscle, mitochondrial biogenesis, PGC-1α, estrogen-related receptor alpha, oxidative stress, fatty acid oxidation, mitochondrial dysfunction, PPARγ coactivator
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adaptation, Physiological, Animals, Dietary Fats, Male, Mice, Inbred ICR, Mitochondria, Muscle, Obesity, Muscle, Skeletal, Estrogen Receptor alpha, Mice
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