导读：  常永生课题组于2017年07月在”Cell Reports” 杂志发表研究论文“Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat”。拟从表观遗传和基因转录调控着手研究米色脂肪的发育和激活，为治疗肥胖提供潜在靶点。

链接：http://www.sciencedirect.com/science/article/pii/S2211124717309002?via=ihub。

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        中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的常永生研究团队通过研究发现SIRT6参与了米色脂肪细胞发育，其对米色脂肪发育及对机体代谢具有重要的意义，此研究拟从表观遗传和基因转录调控着手研究米色脂肪的发育和激活，为治疗肥胖提供潜在靶点。

      【摘要】： Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological "whitening" of brown fat, reduced oxygen (O2) consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis. Moreover, SIRT6 deficiency inhibits the browning of white adipose tissue (WAT) following cold exposure or β3-agonist treatment. Depletion of SIRT6 expression in brown adipocytes reduces expression of thermogenic genes, causing a reduction in cellular respiration. Conversely, SIRT6 overexpression in primary fat cells stimulates the thermogenic program. Mechanistically, SIRT6 interacts with and promotes phospho-ATF2 binding to the PGC-1α gene promoter to activate its expression. The present study reveals a critical role for SIRT6 in regulating thermogenesis of fat.

       本文通讯作者为常永生研究员，共同第一作者姚璐博士和崔肖娜博士。该研究工作得到了国家自然科学基金的支持。

医学分子生物学国家重点实验室