2. Academic Validation
  3. RepSox, a small molecule inhibitor of the TGFβ receptor, induces brown adipogenesis and browning of white adipocytes

RepSox, a small molecule inhibitor of the TGFβ receptor, induces brown adipogenesis and browning of white adipocytes

  • Acta Pharmacol Sin. 2019 Dec;40(12):1523-1531. doi: 10.1038/s41401-019-0264-2.
Wan-Zhi Tu 1 2 3,  Yan-Bin Fu 1 4,  Xin Xie 5 6 7 8
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.
  • 2 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 3 School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
  • 4 Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, 200092, Shanghai, China.
  • 5 CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China. [email protected].
  • 6 University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
  • 7 School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China. [email protected].
  • 8 Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, 200092, Shanghai, China. [email protected].
PMID: 31235818 DOI: 10.1038/s41401-019-0264-2
Abstract

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.

Keywords

RepSox; TGF-β inhibitor; TGF-β receptor; adipocyte; brown adipogenesis; differentiation.

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