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.