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.