RepSox 是一种 TGFβ 受体的小分子抑制剂，可诱导棕色脂肪生成和白色脂肪细胞褐变。,Acta Pharmacologica Sinica

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RepSox 是一种 TGFβ 受体的小分子抑制剂，可诱导棕色脂肪生成和白色脂肪细胞褐变。
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2019-06-24 , DOI: 10.1038/s41401-019-0264-2
Wan-Zhi Tu _{1,

2,

3} , Yan-Bin Fu _{1,

4} , Xin Xie _{1,

2,

3,

4}

Affiliation

与白色脂肪组织 (WAT) 不同，棕色脂肪组织 (BAT) 主要负责通过解耦呼吸链通过产热产生能量消耗。促进棕色脂肪前体细胞的分化和白色脂肪的褐变已成为治疗肥胖症及相关代谢疾病的研究热点。已发现多种分泌因子和多种小分子可促进棕色脂肪生成。在这里，我们报告了单个小分子化合物 RepSox 足以诱导成纤维细胞培养基中小鼠胚胎成纤维细胞 (MEF) 的脂肪生成。RepSox 是转化生长因子-β 受体 I (TGF-β-RI) 的抑制剂，其他 TGF-β 通路抑制剂如 SB431542、LY2157299、A83-01 和曲尼司特也可有效诱导 MEF 的脂肪生成。这些脂肪细胞表达棕色脂肪细胞特异性转录因子和产热基因，并含有大量线粒体并具有高水平的线粒体呼吸活性。更有趣的是，还发现 RepSox 可以促进棕色脂肪前体细胞的分化并诱导白色脂肪前体细胞的褐变。这些发现表明，TGF-β 信号通路抑制剂可能被开发为肥胖和 2 型糖尿病的新疗法。

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

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.

更新日期：2019-06-24

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