Analysis of vanin-1 upregulation and lipid accumulation in hepatocytes in response to a high-fat diet and free fatty acids

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 ectoenz...

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Published in:Journal of Clinical Biochemistry and Nutrition 2012, Vol.51(3), pp.163-169
Main Authors: Motomura, Wataru, Yoshizaki, Takayuki, Takahashi, Nobuhiko, Kumei, Shima, Mizukami, Yusuke, Jang, Seong-Jae, Kohgo, Yutaka
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Language:English
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fatty acids
lipid droplet
nonalcoholic fatty liver disease
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vanin-1
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container_title Journal of Clinical Biochemistry and Nutrition
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creator Motomura, Wataru
Yoshizaki, Takayuki
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Kohgo, Yutaka
description 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.
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subjects fatty acids
lipid droplet
nonalcoholic fatty liver disease
Original
vanin-1
title Analysis of vanin-1 upregulation and lipid accumulation in hepatocytes in response to a high-fat diet and free fatty acids
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