Brown Adipogenic Reprogramming Induced by a Small Molecule

• DOI: 10.1016/j.celrep.2016.12.062
• Publication Date: 2017-01-17T19:45:54Z
• Authors: 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
• Keywords: Tetrahydronaphthalenes; QH301-705.5; Adipose Tissue, White; RXR; adipogenesis; Myoblasts; Mice; 03 medical and health sciences; Oxygen Consumption; Adipose Tissue, Brown; Animals; Retinoid X Receptor gamma; Biology (General); Cells, Cultured; Retinoid X Receptor beta; 0303 health sciences; Adipogenesis; Retinoid X Receptor alpha; Body Weight; bexarotene; Thermogenesis; Cellular Reprogramming; DNA-Binding Proteins; Mice, Inbred C57BL; PPAR gamma; Bexarotene; RNA Interference; C2C12; brown adipocyte

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.