Autor: |
Lu Yao, Xiaona Cui, Qi Chen, Xiaoying Yang, Fude Fang, Jun Zhang, Guoqing Liu, Wanzhu Jin, Yongsheng Chang |
Jazyk: |
angličtina |
Rok vydání: |
2017 |
Předmět: |
|
Zdroj: |
Cell Reports, Vol 20, Iss 3, Pp 641-654 (2017) |
Druh dokumentu: |
article |
ISSN: |
2211-1247 |
DOI: |
10.1016/j.celrep.2017.06.069 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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