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

doi:10.1038/s41401-019-0264-2

	RepSox, a small molecule inhibitor of the TGF beta receptor, induces brown adipogenesis and browning of white adipocytes
	Tu, Wan-zhi1,2,3 ; Fu, Yan-bin 1,4; Xie, Xin1,2,3,4
	2019-12
发表期刊	ACTA PHARMACOLOGICA SINICA (IF:6.9[JCR-2023],7.6[5-Year])
ISSN	1671-4083
EISSN	1745-7254
卷号	40 期号:12 页码:1523-1531
发表状态	已发表
DOI	10.1038/s41401-019-0264-2
摘要	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-beta-RI), other inhibitors of TGF-beta 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-beta signaling pathway might be developed as new therapeutics for obesity and type 2 diabetes.
关键词	RepSox brown adipogenesis TGF-beta receptor TGF-beta inhibitor adipocyte differentiation
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[81730099] ; National Natural Science Foundation of China[81472862]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号	WOS:000500546400003
出版者	NATURE PUBLISHING GROUP
WOS关键词	ADIPOSE-TISSUE ; FAT DEVELOPMENT ; CONVERSION ; DIFFERENTIATION ; THERMOGENESIS ; OBESITY
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104493
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_谢欣组
通讯作者	Xie, Xin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Lab Receptor Based Biomed, Shanghai 200092, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Tu, Wan-zhi,Fu, Yan-bin,Xie, Xin. RepSox, a small molecule inhibitor of the TGF beta receptor, induces brown adipogenesis and browning of white adipocytes[J]. ACTA PHARMACOLOGICA SINICA,2019,40(12):1523-1531.
APA	Tu, Wan-zhi,Fu, Yan-bin,&Xie, Xin.(2019).RepSox, a small molecule inhibitor of the TGF beta receptor, induces brown adipogenesis and browning of white adipocytes.ACTA PHARMACOLOGICA SINICA,40(12),1523-1531.
MLA	Tu, Wan-zhi,et al."RepSox, a small molecule inhibitor of the TGF beta receptor, induces brown adipogenesis and browning of white adipocytes".ACTA PHARMACOLOGICA SINICA 40.12(2019):1523-1531.