THE REGULATION OF HEPATIC LIPASE AND CHOLESTERYL ESTER TRANSFER PROTEIN-ACTIVITY IN THE CHOLESTEROL-FED RABBIT

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) activities are both increased in the rabbit by cholesterol feeding. The in vivo regulation of HL and CETP were explored by examining changes in specific steady-state mRNA levels upon cholesterol feeding. On feeding rabbits cholesterol, HL activity increased 3-fold after 2 days and remained at 2.6-times the control value at 28 days. Specific rabbit HL mRNA levels were assessed by dot blot analysis of liver poly (A) + RNA hybridized with the human HL cDNA. No significant changes in liver HL mRNA accompanied the increase in activity seen at days 2 and 7. At day 28 a modest rise of 46% was observed. A significant rise in CETP activity, evident 7 days after the commencement of cholesterol feeding, was maintained until day 28 when it was 2.4-times the control value. Using the human CETP cDNA as probe, rabbit liver CETP mRNA was also found to increase by day 7, rising to 3.7-times control by day 28. The strong temporal relationship between the rise in CETP activity and mRNA (r = 0.55, P = 0.02) suggests that the regulation of CETP may be primarily effected by the levels of specific mRNA. In contrast, the discordance between levels of lipase activity and mRNA suggests that post-transcriptional events may be more important in the regulation of HL in the cholesterol fed rabbit.