Background: Non-alcoholic steatohepatitis (NASH) is a major health problem based upon abdominal obesity and metabolic syndrome. An improved mouse model of NASH, such as a choline-deficient high fat diet (CDAHFD)-induced dietary model, has been developed. We, previously, have shown that serum total cholesterol (T-cho) and triglyceride (TG) levels, as well as body weight (BW), were decreased in CDAHFD-induced NASH mice, compared to mice fed standard diet (SD). We, therefore, have explored the molecular mechanisms involved in the reduced serum lipids.
Methods: C57BL/6J male mice (specific pathogen-free, 8 weeks old) were fed CDAHFD or SD (10 mice each) for 14 weeks, and then serum lipid profiles, liver histology, hepatic TG levels, and expression levels of genes involved in lipid metabolism in the liver were compared between the two groups. Moreover, correlations between these parameters were explored.
Results: Remarkable lipid accumulation, inflammatory cell infiltration and fibrosis were observed in livers of CDAHFD-fed mice but not in SD-fed mice. Hepatic TG and serum ALT levels were significantly and remarkably higher in CDAHFD-fed mice than in SD-fed mice. In contrast, hepatic MTP mRNA expression, BW, serum T-cho and TG levels were significantly lower in CDAHFD-fed mice than in SD-fed mice. Hepatic MTP mRNA expression levels tended to be correlated with serum T-cho and TG levels and BW, and inversely correlated with hepatic TG and serum ALT levels.
Conclusion: A mouse NASH model induced by CDAHFD showed reduced hepatic MTP expression and serum T-cho and TG levels, and thus may represent a MTP inhibitor-induced NASH in humans.

06 - REDUCED HEPATIC MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN (MTP) EXPRESSION IN A MOUSE MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) INDUCED BY CHOLINE-DEFICIENT HIGH FAT DIET (CDAHFD)