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Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat.

Authors: Yao, Lu  Cui, Xiaona  Chen, Qi  Yang, Xiaoying  Fang, Fude  Zhang, Jun  Liu, Guoqing  Jin, Wanzhu  Chang, Yongsheng 
Citation: Yao L, etal., Cell Rep. 2017 Jul 18;20(3):641-654. doi: 10.1016/j.celrep.2017.06.069.
Pubmed: (View Article at PubMed) PMID:28723567
DOI: Full-text: DOI:10.1016/j.celrep.2017.06.069

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 ß-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 ß3-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.


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RGD Object Information
RGD ID: 13673789
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.