title: Brown Adipogenic Reprogramming Induced by a Small Molecule.
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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Baoming
authors.initials: B
authors.lastname: Nie
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hui
authors.affiliation: Department of Endocrinology, School of Medicine, Nanjing University, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Liufeng
authors.initials: L
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Kuai
authors.initials: K
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ran
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jiashun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Shibing
authors.initials: S
authors.lastname: Tang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D000077610:Bexarotene; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D034622:RNA Interference; D047490:Retinoid X Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D049230:Retinoid X Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047491:Retinoid X Receptor gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D022722:Thermogenesis / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D047495:PPAR gamma; C521133:Prdm16 protein, mouse; D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D047491:Retinoid X Receptor gamma; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000077610:Bexarotene
keywords: C2C12; RXR; adipogenesis; bexarotene; brown adipocyte