Myostatin Regulates Fatty Acid Desaturation and Fat Deposition through MEF2C/miR222/SCD5 Cascade in Pigs
Open accessAbstract
Myostatin (MSTN), associated with the "double muscling" phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.
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By activating SCD5, myostatin catalyzes Δ9 desaturation of FAs, such as conversion of palmitic acid to palmitoleic acid and stearic acid to oleic acid.
“Specifically, by activating stearoyl-CoA desaturase 5 (SCD5), it catalyzes the Δ9 desaturation of FAs, such as the conversion of palmitic acid to palmitoleic acid and of stearic acid to oleic acid [71].”
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 [71]
The Results section (‘MSTN acts via MEF2C/miR222/SCD5 to affect fat deposition’; page not provided) reports that restoring myostatin increased SCD5 expression and the ratios of palmitoleic to palmitic acid and oleic to stearic acid. The Discussion identifies SCD5 as the enzyme that catalyzes those conversions. Thus myostatin promotes desaturation through SCD5, but the source does not say myostatin itself catalyzes the reaction. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMyostatin deficiency enhances activity of lipolytic enzymes CPT1 and CPT2, thereby stimulating β-oxidation of FAs in peripheral tissues and reducing lipid accumulation.
“Conversely, myostatin deficiency enhances the activity of lipolytic enzymes such as CPT1 and CPT2, thereby stimulating the β-oxidation of FAs in peripheral tissues and reducing lipid accumulation [71].”
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 [71]
The Results section reports less fat deposition in MSTN-knockout pigs, but attributes it to the MEF2C/miR222/SCD5 pathway reducing substrates for triglyceride synthesis. The Discussion mentions that MEF2C can activate CPT1β expression, citing prior work; it does not report enhanced CPT1 or CPT2 activity after myostatin deficiency, or establish increased β-oxidation in peripheral tissues. (LLM, conf=0.88)
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Other miscellaneous molecules derived from porcine
Musharraf, S. G., & Akbar, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44211-7.00005-0
- Authors
- Ren, H., Xiao, W., Qin, X., Cai, G., Chen, H., Hua, Z., Cheng, C., Li, X., Hua, W., Xiao, H., Zhang, L., Dai, J., Zheng, X., Zhu, Z., Qian, C., Yao, J., & Bi, Y.
- Affiliations
- Hubei Academy of Agricultural Sciences (CN)
- Corresponding author
- Yao, Jie
- Bi, Yanzhen
- ORCID
- Venue
- Communications Biology
- Published
- 2020-10-23
- Volume
- 3
- Issue
- 1
- Pages
- 612-612
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC7584575
- OpenAlex
- W3093646803
- Cited by
- 54
- References
- 36
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 1
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- AgResearch
- National Natural Science Foundation of China (2016ZX08006-001, 31772577)
- Natural Science Foundation of Hubei Province
- Hubei Academy of Agricultural Sciences (L2018015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- myostatin, MEF2C, SCD5, fatty acid desaturation, fat deposition, adipogenesis, double muscling, Meishan pig, subcutaneous adipose tissue, microRNA target regulation, transcription factor binding, pig breeding
- MeSH terms
- Gene Editing, Animals, Fatty Acids, Promoter Regions, Genetic, Stearoyl-CoA Desaturase, Swine, Sus scrofa, MicroRNAs, Subcutaneous Fat, Myostatin, Gene Knockout Techniques, Transcriptome, MEF2 Transcription Factors
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