Mechanism of the effect of glycosyltransferase GLT8D2 on fatty liver.

Yutao Zhan,Fei Zhao,Dongnian Li,Wei An,Hongshan Wei,Leping Zhong,Ping Xie,Li Li,Lingqiang Zhang,Qujing Gai

doi:10.1186/s12944-015-0040-3

Abstract

BackgroundRecent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver.MethodsRat model of NAFLD was established by induction with high-fat-diet. The GLT8D2 expression in rat liver was examined using immunohistochemistry. Oil Red O staining and triglyceride assay were used to measure the effect of abnormal GLT8D2 expression on lipid accumulation in HepG2 cells. The expression levels of lipid metabolism-related key molecules, namely sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-coA desaturase (SCD), carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP), in HepG2 cells with abnormal GLT8D2 expression were determined by western blot analyses.ResultsThe expression of GLT8D2 was higher in the liver of rats with NAFLD than in the control rats, and GLT8D2 was mainly located around lipid droplets in hepatocytes. GLT8D2 expression increased in steatosis HepG2 cells compared with that in normal HepG2 cells. GLT8D2 positively regulated lipid droplet accumulation and triglyceride content in HepG2 cells. Upregulation or knockdown of GLT8D2 had no effect on the expressions of SREBP-1c, SCD or CPT-1 proteins in HepG2 cells. However, GLT8D2 expression negatively regulated the expression of MTP protein in HepG2 cells.ConclusionGLT8D2 participated in NAFLD pathogenesis possibly by negatively regulating MTP expression. Specific inhibition of GLT8D2 via an antagonistic strategy could provide a potential candidate approach for treatment of NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease in the world [1,2]
We examined the GLT8D2 expression in fatty liver of rat, and the effect of aberrant expression of GLT8D2 on the accumulation of triglyceride and the several key molecules related to the accumulation of triglyceride in HepG2 cells
Inducement of nonalcoholic fatty liver disease (NAFLD) in rat model No obvious steatosis was found in hepatocytes in rats in the control group

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease in the world [1,2]. Glycosyltransferases constitute a large group of enzymes that transfer one or multiple molecules of sugar to a wide range of acceptor molecules such as lipids, proteins, Zhan et al Lipids in Health and Disease (2015) 14:43 hormones, secondary metabolites, and oligosaccharides [12]. These enzymes play key roles in many fundamental biological processes underpinning human health and disease, such as cell signalling, cellular adhesion, carcinogenesis, and cell wall biosynthesis in human pathogens [13]. Recent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver

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Conclusion