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

详细信息    查看全文

• 作者：Yu-Sheng Lai^a ; Tzu-Ching Yang^a ; Po-Yuan Chang^b ; Shwu-Fen Chang^c ; Shu-Li Ho^d ; Hui-Ling Chen^d ; ^{hlchen9@ntu.edu.tw" class="auth_mail" title="E-mail the corresponding author} ; Shao-Chun Lu^a ; ^{lsc@ntu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：α-SMA ; α-smooth muscle actin ; ALT ; alanine aminotransferase ; AST ; aspartate aminotransferase ; HE ; hematoxylin&ndash ; eosin ; HFC ; high-fat ; high-cholesterol ; LDL(&minus ; ) ; electronegative LDL ; MPO ; myeloperoxidase ; nLDL ; native LDL ; NAFLD ; nonalcoholic fatty liver disease ; NASH ; nonalcoholic steatohepatitis ; oxLDL ; oxidized LDL ; PBS ; phosphate-buffered saline ; TC ; total cholesterol ; TG ; triglyceride
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：30
• 期：Complete
• 页码：44-52
• 全文大小：1680 K

文摘

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.