Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters
Resource
J. Nutr. Biochem., 30, 44-52
Journal
J. Nutr. Biochem.
Journal Issue
30
Pages
44-52
Date Issued
2016
Date
2016
Author(s)
Abstract
The pathogenesis of nonalcoholic steatohepatitis (NASH), like that of atherosclerosis, involves lipid accumulation, inflammation and fibrosis. Recent studies suggest that oxidized LDL (oxLDL) may be a risk factor for NASH, but oxLDL levels were not directly measured in these studies. The aim of this study was to examine whether there was an association between electronegative LDL [LDL(-)], a mildly oxLDL found in the blood, and the development of NASH using two animal models. Golden Syrian hamsters and C57BL/6 mice were fed a high-fat, high-cholesterol (HFC) diet for 6 or 12 weeks, then liver lipid and histopathology, plasma lipoprotein profile and LDL(-) levels were examined. The HFC-diet-fed hamsters and mice had similar levels of hepatic lipid but different histopathological changes, with microvesicular steatosis, hepatocellular hypertrophy, inflammation and bridging fibrosis in the hamsters, but only in mild steatohepatitis with low inflammatory cell infiltration in the mice. It also resulted in a significant increase in plasma levels of LDL cholesterol and LDL(-) in hamsters, but only a slight increase in mice. Moreover, enlarged Kupffer cells, LDL(-) and accumulation of unesterified cholesterol were detected in the portal area of HFC-diet-fed hamsters, but not HFC-diet-fed mice. An in vitro study showed that LDL(-) from HFC-diet-fed hamsters induced TNF-alpha secretion in rat Kupffer cell through a LOX-1-dependent pathway. Our results strongly suggest that LDL(-) is one of the underlying causes of hepatic inflammation and plays a critical role in the development of NASH. (C) 2015 Elsevier Inc. All rights reserved.
Subjects
Electronegative LDL (LDL(-))
Hamster
Hepatic inflammation
Nonalcoholic steatohepatitis (NASH)
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1)
SDGs
Other Subjects
alanine aminotransferase; apolipoprotein B; aspartate aminotransferase; cholesterol; interleukin 1beta; interleukin 6; low density lipoprotein; low density lipoprotein cholesterol; oxidized low density lipoprotein receptor 1; triacylglycerol; tumor necrosis factor alpha; cholesterol intake; low density lipoprotein; alanine aminotransferase blood level; animal cell; animal experiment; animal model; animal tissue; Article; aspartate aminotransferase blood level; cell infiltration; cholesterol blood level; cholesterol diet; cholesterol liver level; controlled study; hepatitis; histopathology; in vitro study; in vivo study; Kupffer cell; lipid liver level; liver fibrosis; liver perfusion; macrophage; male; mouse; nonalcoholic fatty liver; nonhuman; pathogenesis; rat; Syrian hamster; triacylglycerol blood level; administration and dosage; animal; C57BL mouse; cholesterol intake; hamster; lipid diet; Mesocricetus; Non-alcoholic Fatty Liver Disease; Animals; Cholesterol, Dietary; Cricetinae; Diet, High-Fat; Lipoproteins, LDL; Male; Mesocricetus; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease