title: Angiogenic factor with G patch and FHA domains 1 (Aggf1) promotes hepatic steatosis in mice.
abstract: Increased uptake of nutrients coupled with reduced activity leads to the development of a host of metabolic disorders in humans. In the present study we examined the role of angiogenic factor with G patch and FHA domains 1 (Aggf1) in the pathogenesis of steatosis, characterized by accumulation of lipids in the liver and consequently hepatic insulin resistance. We report here that Aggf1 expression was up-regulated in the liver in both genetically predisposed and diet-induced mouse model of steatosis. Aggf1 expression was also stimulated by free fatty acids in primary hepatocytes. Over-expression of Aggf1 in mice promoted steatosis. On the contrary, Aggf1 depletion ameliorated steatosis in mice. Mechanistically, Aggf1 activated the expression of gluconeogenesis gene and skewed the insulin signaling pathway to induce insulin resistance. Taken together, our data suggest that Aggf1 plays a role in steatosis in vivo and as such may be a new target in the development of therapeutics solutions against steatosis.
authors.affiliation: College of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China. Electronic address: zhoubisheng@126.com.
authors.forename: Bisheng
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China. Electronic address: yjxu@njmu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation
chemical_list: C000619510:Aggf1 protein, mouse; D042501:Angiogenic Proteins; D007328:Insulin; D005947:Glucose
keywords: Aggf1; Gluconeogenesis; Hepatocyte; Insulin resistance; Steatosis