title: Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.
abstract: We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model.
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Han
authors.affiliation: b Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences , Shenzhen , China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Liu
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.
authors.forename: Changhu
authors.initials: C
authors.lastname: Xue
authors.affiliation: c Health and Nutrition Science, Nishi kyushu University , Kanzaki , Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Yanagita
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.|d Faculty of Medicine , Memorial University , Saint John's , Canada.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: a College of Food Science and Engineering, Ocean University of China , Qingdao , China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D015870:Gene Expression; D005943:Gluconeogenesis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000503:physiopathology*; D009963:Orotic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D007328:Insulin; D009963:Orotic Acid
keywords: fatty liver; glucose intolerance; insulin signaling; lipids