title: ATF4 deficiency protects mice from high-carbohydrate-diet-induced liver steatosis.
abstract: Chronic feeding of HCD (high-carbohydrate diet) is one of the major contributors to the prevailing of metabolic diseases. ATF4 (activating transcription factor 4) has been shown to play an important role in the regulation of glucose metabolism and obesity development; however, it is unclear how ATF4(-/-) mice respond to HCD. In the present study, we show that 8 weeks of HCD results in significant higher accumulation of TAGs (triacylglycerols) in livers and impairment in glucose tolerance in ATF4(+/+) mice, but not in ATF4(-/-) mice, compared with those on a normal diet. Meanwhile, energy expenditure is further enhanced by HCD in ATF4(-/-) mice. Moreover, we show that ATF4 deficiency suppresses HCD-induced SCD1 (stearoyl-CoA desaturase 1) expression, furthermore, oral supplementation of the main product of SCD1 oleate (18:1) increases TAG accumulation in livers of ATF4(-/-) mice. Taken together, these results suggest that ATF4 deficiency is protective for HCD-induced hepatic steatosis and impairment of glucose tolerance and insulin sensitivity. Furthermore, the resistance to hepatic steatosis is at least in part due to suppression of SCD1 expression under HCD.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Houkai
authors.initials: H
authors.lastname: Li
authors.forename: Qingshu
authors.initials: Q
authors.lastname: Meng
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D051701:Activating Transcription Factor 4 / Q000172:deficiency* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D004032:Diet; D004040:Dietary Carbohydrates; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019301:Oleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: C081452:Atf4 protein, mouse; D004040:Dietary Carbohydrates; D007328:Insulin; D014280:Triglycerides; D051701:Activating Transcription Factor 4; D019301:Oleic Acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase