Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion?

Ursula Andreo,Steven J.R. Meex,Janet D. Sparks,Edward A. Fisher

doi:10.1194/jlr.d008888

Ursula Andreo, Steven J.R. Meex + Show 2 more

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https://doi.org/10.1194/jlr.d008888

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Abstract

Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipoproteins (VLDL) from liver. The hepatoma HepG2 cell line has been the cell line of choice for the study of synthesis and secretion of human apoB-100. Despite the general use of HepG2 cells to study apoB100 metabolism, they secrete relatively dense, lipid-poor particles compared with VLDL secreted in vivo. Recently, Huh-7 cells were adopted as an alternative model to HepG2 cells, with the implicit assumption that Huh-7 cells were superior in some respects of lipoprotein metabolism, including VLDL secretion. In this study we addressed the hypothesis that the spectrum of apoB100 lipoprotein particles secreted by Huh-7 cells more closely resembles the native state in human liver. We find that Huh-7 cells resemble HepG2 cells in the effects of exogenous lipids, microsomal triglyceride transfer protein (MTP)-inhibition, and proteasome inhibitors of apoB100 secretion, recovery, and degradation. In contrast to HepG2 cells, however, MEK-ERK inhibition does not correct the defect in VLDL secretion. Huh-7 cells do not appear to offer any advantages over HepG2 cells as a general model of human apoB100-lipoprotein metabolism.

Highlights

Apolipoprotein-B100 is the essential protein for the assembly and secretion of very low density lipoproteins (VLDL) from liver
We first investigated the hypothesis that the buoyant density of apoB100-containing lipoprotein particles secreted by Huh-7 cells more closely resembles that of VLDL particles secreted by human liver in vivo, in contrast to the LDL-like particles secreted by HepG2 cells
HepG2 cells secreted 70% of their apoB100 as lipoproteins with density of р1.06 g/ml (LDL-sized), compared with 95% secreted by Huh-7 cells

Summary

Introduction

Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipoproteins (VLDL) from liver. Despite the general use of HepG2 cells to study apoB100 metabolism, they secrete relatively dense, lipid-poor particles compared with VLDL secreted in vivo. Many studies of human apoB100 metabolism have used the hepatoma HepG2 cell line Despite their general use, HepG2 cells secrete relatively dense, lipid-poor apoB100-containing particles, unlike the buoyant VLDL particles secreted in vivo by mammalian liver. An alternative human cell model with a more native level of VLDL secretion would strongly benefit the lipoprotein field and might advance novel insights into apoB100 metabolism. Huh-7 cells were proposed as a superior human hepatic cell model for the study of apoB100 metabolism and VLDL secretion [see references 2, 3)] and are becoming more widely used for these purposes [see references [4, 5]].

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