title: ATF4 regulates lipid metabolism and thermogenesis.
abstract: 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 beta-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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000502:physiology*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D050356:Lipid Metabolism / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D022722:Thermogenesis / Q000235:genetics*
chemical_list: C081452:Atf4 protein, mouse; D051701:Activating Transcription Factor 4