Liver X receptor a (LXRa) and sterol regulatory element binding protein-1c (SREBP-1c) were studied in rats with nonalcoholic steatohepatitis (NASH) induced by a high-fat diet. Forty 5-week-old rats were fed either a high-fat diet (n = 30) or a normal diet (n = 10) for 9, 13 or 17 weeks. The mRNA and protein levels for LXRa and SREBP-1c were measured at each time point, as was fatty acid synthase (FAS) activity and the serum levels of free fatty acid (FFA) and triglyceride (TG). The mRNA and protein levels for LXRa and SREBP-1c, FAS activity and serum levels of FFA and TG all significantly increased from week 9 in the high-fat diet rats versus controls. In conclusion, a high-fat diet upregulates LXRa which, in turn, upregulates SREBP1c, increasing the activity of FAS and FFA and accumulation of TG in hepatocytes. Thus, LXRa and SREBP-1c contribute to the development of NASH.
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