Brown Adipogenic Reprogramming Induced by a Small Molecule

Publication date: 17 January 2017
Source:Cell Reports, Volume 18, Issue 3
Author(s): 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
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.

Graphical abstract

Teaser

Employing high-throughput phenotypic screening, Nie et al. identify a retinoid X receptor agonist, bexarotene, as a hit compound that reprograms myoblasts into brown adipocytes. This reprograming requires a transcription coregulator, PRDM16, and the browning capacity of bexarotene was verified in mice. Overall, these insights point to the role of RXRs as master regulators of brown and beige fat development and activation and open a potential strategy for therapeutic manipulation of brown/beige fat function.


http://ift.tt/2k3qByz