High dietary cholesterol and ovariectomy in rats repress gene expression of key markers of VLDL and bile acid metabolism in liver.

Background: The purpose of the study was to evaluate the effects of high dietary cholesterol in ovariectomized (Ovx) rats on several key markers of hepatic cholesterol and bile acid metabolism.

Method: Ovx and sham operated (Sham) rats were given either a standard diet (SD), a SD diet supplemented with 0.25% cholesterol (SD + Chol), or a high fat diet supplemented with 0.25% cholesterol (HF + Chol) for 5 weeks.

Results: Ovx was associated with higher (P < 0.05) liver total cholesterol (TC) under the SD and the SD + Chol diet, while liver triglyceride (TG) content was higher in Ovx than in Sham rats in all 3 diet conditions. Surprisingly, the SD + Chol diet was associated with lower (P < 0.001) plasma TC and TG levels in Ovx than in Sham rats, suggesting a decrease in VLDL secretion. Accordingly, several transcripts of key markers of VLDL synthesis including microsomal TG transfer protein (Mttp) and Apob-100 were decreased (P < 0.05) in Ovx compared to Sham rats under the three dietary conditions and even more so for Mttp and Apob-100 when rats were fed the SD + Chol diet. Transcripts of bile acid transporters including bile salt export pump (Bsep) and Na + -taurocholate cotransporting polypeptide (Ntcp) were decreased by the addition of cholesterol to the SD diet in both Ovx and Sham rats.

Conclusion: These results indicate that a high cholesterol feeding and ovariectomy combine to reduce the gene expression of key markers of VLDL synthesis suggesting a reduction in excretion of cholesterol from the liver.