Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice
Open accessAbstract
Aims/hypothesis Although myostatin-null (Mstn (-/-)) mice fail to accumulate fat in adipose tissue when fed a high-fat diet (HFD), little is known about the molecular mechanism(s) behind this phenomenon. We therefore sought to identify the signalling pathways through which myostatin regulates accumulation and/or utilisation of fat.Methods Wild-type, Mstn (-/-) and wild-type mice treated with soluble activin type IIB receptor (sActRIIB) were fed a control chow diet or an HFD for 12 weeks. Changes in gene expression were measured by microarray and quantitative PCR. Histological changes in white adipose tissue were assessed together with peripheral tissue fatty acid oxidation and changes in circulating hormones following HFD feeding.Results Our results demonstrate that inactivation of myostatin results in reduced fat accumulation in mice on an HFD. Molecular analysis revealed that metabolic benefits, due to lack of myostatin, are mediated through at least two independent mechanisms. First, lack of myostatin increased fatty acid oxidation in peripheral tissues through induction of enzymes involved in lipolysis and in fatty acid oxidation in mitochondria. Second, inactivation of myostatin also enhanced brown adipose formation in white adipose tissue of Mstn (-/-) mice. Consistent with the above, treatment of HFD-fed wild-type mice with the myostatin antagonist, sActRIIB, reduced the obesity phenotype.Conclusions/interpretation We conclude that absence of myostatin results in enhanced peripheral tissue fatty acid oxidation and increased thermogenesis, culminating in increased fat utilisation and reduced adipose tissue mass. Taken together, our data suggest that anti-myostatin therapeutics could be beneficial in alleviating obesity.
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Absence of myostatin in Mstn-/- mice results in increased gene expression of enzymes and transcription factors involved in lipolysis, mitochondrial fatty acid oxidation, and white adipose tissue browning, as well as decreased visceral adipose tissue mass.
“Its absence in Mstn-/- mice results in increased gene expression of enzymes and transcription factors involved in lipolysis, mitochondrial FAO, and WAT browning, as well as decreased VAT mass [132].”
Reducing myostatin-mediated inhibition of WAT lipolysis.
“reducing myostatin-mediated inhibition of WAT lipolysis [132].”
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- Authors
- Zhang, C., McFarlane, C., Lokireddy, S., Masuda, S., Ge, X., Gluckman, P. D., Sharma, M., & Kambadur, R.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Nanyang Technological University (SG)
- National University of Singapore (SG)
- Corresponding author
- Kambadur, R.
- Venue
- Diabetologia
- Published
- 2011-09-17
- Volume
- 55
- Issue
- 1
- Pages
- 183-193
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2146923536
- Cited by
- 192
- References
- 38
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 15 · 2023: 10 · 2022: 13 · 2021: 19 · 2020: 16 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 21 · 2014: 14 · 2013: 19 · 2012: 13
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-12-11)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline - JCU (James Cook University) (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Funders
- Agency for Science, Technology and Research
- Singapore Institute for Clinical Sciences
- Nanyang Technological University
- Directorate for Biological Sciences
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- myostatin, diet-induced obesity, high-fat diet, fatty acid oxidation, brown adipose tissue, white adipose tissue, thermogenesis, lipolysis, fat deposition, mitochondrial fatty acid oxidation
- MeSH terms
- Animals, Adipose Tissue, Brown, Fatty Acids, Gene Expression Regulation, Lipolysis, Male, Mice, Inbred C57BL, Muscle Proteins, Obesity, Oxidation-Reduction, RNA, Messenger, Solubility, Mice, Knockout, Muscle, Skeletal, Anti-Obesity Agents, Gene Expression Profiling, Activin Receptors, Type II, Adiposity, Mice, Myostatin, Molecular Targeted Therapy, Diet, High-Fat
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