Effects of Myostatin Gene Knockout on White Fat Browning and Related Gene Expression in Type 2 Diabetic Mice
Open accessAbstract
BACKGROUND: Myostatin (Mstn) plays an important role in adipocyte growth, differentiation and metabolism, leading to the development of obesity. OBJECTIVES: We aimed to explore the effect of Mstn on white fat browning in a mouse model of type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Twelve wild-type (WT), 12 heterozygous (Mstn(+/-)) and 12 homozygous (Mstn(-/-)) male mice were randomly divided into 6 groups: WT, Mstn(+/-), Mstn(-/-), WT+DM, Mstn(+/-)+DM, and Mstn(-/-)+DM. The first 3 groups were fed normal chow, while the last 3 were fed high-fat diet and administered streptozotocin to generate T2DM. Subsequently, body mass, length, and white and brown fat masses were measured, after which Lee's index, white-brown ratio and fat index were calculated. The serum free fatty acid (FFA) levels were detected using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was used to analyze white and brown fat cell morphology. The relative expression levels of peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), uncoupling protein 1 (UCP1), and cluster of differentiation 137 (CD137) protein were determined with western blotting. RESULTS: The Mstn(-/-) group displayed higher levels of PPARγ, PGC-1α and CD137 proteins in white and brown fat compared to the WT and Mstn(+/-) groups, while the expression level of UCP1 protein in the Mstn(-/-) group was higher than in the WT group. The expression levels of PPARγ, PGC-1α, UCP1, and CD137 proteins in the WT+DM group were lower than in the WT group. Moreover, PPARγ, PGC-1α, UCP1, and CD137 proteins were more highly expressed in the Mstn(-/-)+DM group compared to the WT+DM and Mstn(+/-)+DM groups. CONCLUSIONS: The Mstn gene inhibition antagonizes obesity phenotypes, such as white fat accumulation and lipid metabolism derangement caused by T2DM, thus promoting white fat browning.
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Myostatin plays a pivotal role in adipose tissue plasticity by modulating browning of WAT through AMPK-PGC-1α-FNDC5 axis, a process wherein white adipocytes acquire characteristics of brown adipocytes, including increased mitochondrial content and UCP1 expression, thereby increasing thermogenesis and energy expenditure.
“Myostatin plays a pivotal role in adipose tissue plasticity by modulating the browning of WAT through the AMPK-PGC-1α-FNDC5 axis, a process wherein white adipocytes acquire the characteristics of brown adipocytes, including increased mitochondrial content and the expression of UCP1, thereby increasing thermogenesis and energy expenditure [68,69].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [69]
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- Authors
- Cheng, J., Lee, J., Liu, Y., Wang, Y., Duan, M., & Zeng, Z.
- Affiliations
- Zhengzhou University (CN)
- Kyonggi University (KR)
- Venue
- Advances in Clinical and Experimental Medicine
- Publisher
- Wroclaw Medical University
- Published
- 2023-10-13
- Volume
- 33
- Issue
- 6
- Pages
- 609-617
- ISSN
- 1899-5276 (ISSN-L)
- OpenAlex
- W4387598891
- Cited by
- 7
- References
- 13
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advances in Clinical and Experimental Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- myostatin, white adipose tissue browning, brown adipose tissue, type 2 diabetes, obesity, PPARγ, PGC-1α, UCP1, 4-1BB, free fatty acids, lipid metabolism, high-fat diet, streptozotocin-induced diabetes, gene expression, adipogenesis, fat index, Lee's index
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Male, Mice, Knockout, Mice, Adipose Tissue, White, Myostatin, Diet, High-Fat
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