Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Cholesterol as a key factor in the development of NAFLD in high fat fed mice (#234)

Songpei Li 1 , Xiaoyi Zeng 1 , Xiu Zhou 1 , Hao Wang 1 , Eunjung Jo 1 , Zhisheng Yao 1 , Juan Molero 1 , Aimin Xu 2 , Jiming Ye 1
  1. Lipid Biology and Metabolic Disease, School of Health Sciences, RMIT University, Melbourne, VIC, Australia
  2. Department of Medicine, University of Hong Kong, Hong Kong, China
Non-alcoholic fatty liver disease (NAFLD) is closely related to dyslipidaemia. The present study investigated the role of dietary cholesterol and high fat in the development of NAFLD in relation to metabolic syndrome. We fed mice with chow (CH), chow with 0.2% cholesterol (CHC), high fat (HF) and HF with cholesterol (HFC) for 17 weeks. Addition of cholesterol in CH and HF diet did not affect food intake, body weight gain and the weight of epididymal fat compared with their corresponding controls. Dietary cholesterol moderately attenuated HF induced glucose intolerance by 35% reduction in GTT iAUC and increased liver cholesterol by 95%. However, the increased hepatic TG content by HF was not influenced by cholesterol. The plasma levels of ALT was increased by ~80% in the HFC group (vs HF) but remained normal in other groups, indicating that addition of cholesterol in HF diet induced liver injury. Further examination of the liver revealed a 2-fold increase in TNFa mRNA expression in the HFC groups (vs HF). This was associated with marked suppressions of PGC1a mRNA expression (by 63%) and fatty acid oxidation (by 26%) in the HFC group (vs HF). In comparison, addition of cholesterol in chow diet did not show any of these effects despite a 30% of increase in liver cholesterol content, suggesting that the effect of cholesterol is specific in the HF mice. Removal of cholesterol from the HF diet for 5 weeks was able to reduce plasma ALT and liver cholesterol content and TNFa mRNA expression to the normal levels but suppressed the PGC1a mRNA expression and fatty acid oxidation in the liver were not improved. Our findings suggest that cholesterol plays a critical role in mitochondrial dysfunction and the development of NAFLD by inducing inflammatory response in HF mice.