Brown Adipogenic Reprogramming Induced by a Small Molecule
Baoming Nie,
Tao Nie,
Xiaoyan Hui,
Ping Gu,
Liufeng Mao,
Kuai Li,
Ran Yuan,
Jiashun Zheng,
Haixia Wang,
Ke Li,
Shibing Tang,
Yu Zhang,
Tao Xu,
Aimin Xu,
Donghai Wu,
Sheng Ding
Affiliations
Baoming Nie
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Tao Nie
Central Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou 510630, China
Xiaoyan Hui
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
Ping Gu
Department of Endocrinology, School of Medicine, Nanjing University, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China
Liufeng Mao
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
Kuai Li
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
Ran Yuan
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
Jiashun Zheng
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Haixia Wang
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Ke Li
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Shibing Tang
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Yu Zhang
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Tao Xu
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Aimin Xu
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
Donghai Wu
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China
Sheng Ding
Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
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.
