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Cell Rep. 2017 Jan 17;18(3):624-635. doi: 10.1016/j.celrep.2016.12.062.

Brown Adipogenic Reprogramming Induced by a Small Molecule.

Author information

1
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Central Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou 510630, China; CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
3
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
4
Department of Endocrinology, School of Medicine, Nanjing University, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China.
5
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
6
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
7
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: wu_donghai@gibh.ac.cn.
8
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sheng.ding@gladstone.ucsf.edu.

Abstract

Brown adipose tissue (BAT) has attracted considerable research interest because of its therapeutic potential to treat obesity and associated metabolic diseases. Augmentation of brown fat mass and/or its function may represent an attractive strategy to enhance energy expenditure. Using high-throughput phenotypic screening to induce brown adipocyte reprogramming in committed myoblasts, we identified a retinoid X receptor (RXR) agonist, bexarotene (Bex), that efficiently converted myoblasts into brown adipocyte-like cells. Bex-treated mice exhibited enlarged BAT mass, enhanced BAT function, and a modest browning effect in subcutaneous white adipose tissue (WAT). Expression analysis showed that Bex initiated several "browning" pathways at an early stage during brown adipocyte reprogramming. Our findings suggest RXRs as new master regulators that control brown and beige fat development and activation, unlike the common adipogenic regulator PPARγ. Moreover, we demonstrated that selective RXR activation may potentially offer a therapeutic approach to manipulate brown/beige fat function in vivo.

KEYWORDS:

C2C12; RXR; adipogenesis; bexarotene; brown adipocyte

PMID:
28099842
DOI:
10.1016/j.celrep.2016.12.062
[Indexed for MEDLINE]
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