RepSox, a small molecule inhibitor of the TGFβ receptor, induces brown adipogenesis and browning of white adipocytes.
Open accessAbstract
Unlike white adipose tissue (WAT), brown adipose tissue (BAT) is mainly responsible for energy expenditure via thermogenesis by uncoupling the respiratory chain. Promoting the differentiation of brown fat precursor cells and the browning of white fat have become a research hotspot for the treatment of obesity and associated metabolic diseases. Several secreted factors and a number of small molecules have been found to promote brown adipogenesis. Here we report that a single small-molecule compound, RepSox, is sufficient to induce adipogenesis from mouse embryonic fibroblasts (MEFs) in fibroblast culture medium. RepSox is an inhibitor of the transforming growth factor-beta receptor I (TGF-β-RI), other inhibitors of TGF-β pathway such as SB431542, LY2157299, A83-01, and Tranilast are also effective in inducing adipogenesis from MEFs. These adipocytes express brown adipocyte-specific transcription factors and thermogenesis genes, and contain a large number of mitochondria and have a high level of mitochondrial respiratory activity. More interestingly, RepSox has also been found to promote the differentiation of the brown fat precursor cells and induce browning of the white fat precursor cells. These findings suggest that inhibitors of TGF-β signaling pathway might be developed as new therapeutics for obesity and type 2 diabetes.
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Chemical cocktails containing CHIR99021 and E-616452 can induce direct reprogramming between differentiated cell states.
“Various research groups have observed that chemical cocktails containing CHIR99021 and E-616452 can induce direct reprogramming between differentiated cell states [70, 71].”
From Chemically induced reprogramming to reverse cellular aging (2023) · cites this paper as [71]
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- Authors
- Tu, W.-Z., Fu, Y.-B., & Xie, X.
- Affiliations
- Tongji University (CN)
- Corresponding author
- Xie, Xin
- ORCID
- Xie, Xin
- Venue
- Acta Pharmacologica Sinica
- Published
- 2019-06-24
- Volume
- 40
- Issue
- 12
- Pages
- 1523-1531
- ISSN
- 0253-9756 (ISSN-L)
- 1671-4083
- 1745-7254
- PMC
- PMC7471457
- OpenAlex
- W2955460395
- Cited by
- 33
- References
- 39
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 3 · 2020: 3
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Pharmacologica Sinica (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2017YFA0104002, 81730099, 81472862, 81425024)
- Chinese Academy of Sciences (XDA16010202)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- RepSox, brown adipogenesis, white adipocyte browning, brown adipose tissue, thermogenesis, mitochondrial respiration, mouse embryonic fibroblasts, obesity treatment, type 2 diabetes
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Animals, Adipose Tissue, Brown, Cell Differentiation, Fibroblasts, Mice, Inbred C57BL, Pyrazoles, Pyridines, Gene Expression, Adipogenesis, Adipose Tissue, White, Adipocytes, Brown, Adipocytes, White
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