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Activation of PPARγ2 by PPARγ1 through a functional PPRE in transdifferentiation of myoblasts to adipocytes induced by EPA
Open accessAbstract
PPARγ and Wnt signaling are central positive and negative regulators of adipogenesis, respectively. Here we identified that, eicosapentaenoic acid (EPA) could effectively induce the transdifferentiation of myoblasts into adipocytes through modulation of both PPARγ expression and Wnt signaling. During the early stage of transdifferentiation, EPA activates PPARδ and PPARγ1, which in turn targets β-catenin to degradation and down-regulates Wnt/β-catenin signaling, such that the myogenic fate of myoblasts could be switched to adipogenesis. In addition, EPA up-regulates the expression of PPARγ1 by activating RXRα, then PPARγ1 binds to the functional peroxisome proliferator responsive element (PPRE) in the promoter of adipocyte-specific PPARγ2 to continuously activate the expression of PPARγ2 throughout the transdifferentiation process. Our data indicated that EPA acts as a dual-function stimulator of adipogenesis that both inhibits Wnt signaling and induces PPARγ2 expression to facilitate the transdifferentiation program, and the transcriptional activation of PPARγ2 by PPARγ1 is not only the key factor for the transdifferentiation of myoblasts to adipocytes, but also the crucial evidence for successful transdifferentiation. The present findings provided insight for the first time as to how EPA induces the transdifferentiation of myoblasts to adipocytes, but also provide new clues for strategies to prevent and treat some metabolic diseases.
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Very high concentrations (200-600 μM) of EPA added to mice C2C12 myoblasts during proliferation for up to 10 days induce transdifferentiation to adipocytes.
“For example, very high concentrations (200–600 μM) of EPA added to mice C2C12 myoblasts during proliferation for up to 10 days induce transdifferentiation to adipocytes [139].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [139]
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Metadata
- Authors
- Luo, H., Zhou, Y., Hu, X., Peng, X., Wei, H., Peng, J., & Jiang, S.
- Affiliations
- Huazhong Agricultural University (CN)
- Corresponding author
- Peng, Jian
- Jiang, Siwen
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2015-06-17
- Volume
- 14
- Issue
- 12
- Pages
- 1830-1841
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC4614827
- OpenAlex
- W1751904874
- Cited by
- 36
- References
- 44
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University
- National Natural Science Foundation of China (31272457)
- Natural Science Foundation of Hubei Province (2013PY047, 2013CFA010)
- Fundamental Research Funds for the Central Universities (2013PY047, 2013CFA010, 2007-620)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- eicosapentaenoic acid, PPARγ1, PPARγ2, PPARδ, RXRα, Wnt/β-catenin signaling, adipogenesis, metabolic disorders
- MeSH terms
- Animals, Base Sequence, Cell Line, Cell Nucleus, Humans, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Eicosapentaenoic Acid, Signal Transduction, Transcriptional Activation, Adipocytes, Response Elements, Myoblasts, PPAR delta, PPAR gamma, Wnt Proteins, beta Catenin, Mice, Cell Transdifferentiation, Real-Time Polymerase Chain Reaction
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