Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons with high and low lipemic responses to dietary lipids

Acyl–coenzyme A:cholesterol acyltransferase (ACAT) 1 and ACAT2 play an important role in cellular cholesterol esterification and thus modulate intestinal cholesterol absorption and hepatic lipoprotein secretion. The relative expression levels of ACAT1 and ACAT2 in human tissues differ from those in other animals, including nonhuman primates. The present study compared the relative expression levels of ACAT1 and ACAT2 in baboons with high and low lipemic responses to dietary lipids. We isolated RNA and prepared cDNA from frozen liver and small intestine from high- and low-responding pedigreed baboons necropsied after consuming a high-cholesterol and high-fat diet for 18 months. The expression of ACAT1 and ACAT2 was measured by TaqMan real-time quantitative PCR normalized to 18s ribosomal RNA. The expression of ACAT1 was higher than that of ACAT2 in the liver, whereas the expression of ACAT2 was higher than that of ACAT1 in the duodenum and jejunum. There was no difference in the expression of ACAT1 or ACAT2 in the liver and intestine between high- and low-responding baboons except that the expression of ACAT1 was higher in the duodenum of high responders than in that of low responders. Western blot analysis also showed a higher level of ACAT1 protein in the duodenum of high responders than in that of low responders. There was a significant correlation between duodenal ACAT expression levels and total plasma cholesterol concentration in baboons. These results suggest that differences in ACAT1 expression may affect plasma cholesterol concentration and partly affect diet-induced hyperlipidemia.