Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters

Yu Sheng Lai, Tzu Ching Yang, Po Yuan Chang, Shwu Fen Chang, Shu Li Ho, Hui Ling Chen, Shao Chun Lu

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24 引文 斯高帕斯(Scopus)


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-α 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.

頁(從 - 到)44-52
期刊Journal of Nutritional Biochemistry
出版狀態已發佈 - 4月 1 2016

ASJC Scopus subject areas

  • 分子生物學
  • 營養與營養學
  • 生物化學
  • 臨床生物化學
  • 內分泌學、糖尿病和代謝


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