title: Analysis of vanin-1 upregulation and lipid accumulation in hepatocytes in response to a high-fat diet and free fatty acids.
abstract: High-fat diet is one of the causes of nonalcoholic fatty liver disease. We have previously demonstrated that high-fat diet induces upregulation of adipose differentiation-related protein mRNA expression accompanied by lipid droplet formation in mouse liver. Vanin-1 is a ubiquitous epithelial ectoenzyme that has pantetheinase activity and produces cysteamine, a potent endogenous antioxidant. In the present study, we analyzed the expression of hepatic vanin-1 mRNA following the administration of a high-fat diet in mice as well as free fatty acids in hepatocyte cultures and speculated its possible mechanism. Vanin-1 mRNA levels in the livers of mice were upregulated within a day of the high-fat diet, even before the expression of adipose differentiation-related protein mRNA and lipid accumulation. An in vitro analysis using HuH-7 cells revealed a significant upregulation of vanin-1 mRNA by as low as 0.01 mM oleic acid; however, lipid accumulation in hepatocytes was not affected at this concentration. Furthermore, vanin-1 mRNA was differentially upregulated by various free fatty acids irrespective of the grade of lipid accumulation. These findings indicate that the upregulation of vanin-1 precedes lipid accumulation and is differentially mediated by various types of free fatty acids in the model, presenting vanin-1 as a novel player in the pathogenesis of nonalcoholic fatty liver disease.
authors.affiliation: Department of Microbiology and Immunochemistry, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Motomura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shima
authors.initials: S
authors.lastname: Kumei
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizukami
authors.forename: Seong-Jae
authors.initials: SJ
authors.lastname: Jang
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo