Volume 20, No 2, Feb 2010

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 20 Issue 2, February 2010: 174-184

ORIGINAL ARTICLES

ATF4 regulates lipid metabolism and thermogenesis

Chunxia Wang, Zhiying Huang, Ying Du, Ying Cheng, Shanghai Chen and Feifan Guo

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China Correspondence: Feifan Guo,(ffguo@sibs.ac.cn)

Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4-deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 (UCP2) and β-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue (WAT), suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue (BAT), suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.

Cell Research (2010) 20:174-184. doi: 10.1038/cr.2010.4; published online 12 January 2010

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