Dietary regulation of cholesterol esterase mRNA level in rat pancreas

This study investigates the effect of a high fat/high cholesterol diet on cholesterol esterase biosynthesis in rat pancreas. Results showed that rats fed a high fat/high cholesterol diet, with or without bile salt supplementation, exhibited increased levels of pancreatic cholesterol esterase mRNA. An average of a 2-fold increase in cholesterol esterase mRNA was observed after 1 day of feeding the atherogenic diet. A maximal 3- to 4-fold induction was observed after 4 days on the special diet. The level of pancreatic cholesterol esterase mRNA declined subsequently, resulting in a new steady state level that remained significantly higher than cholesterol esterase mRNA level in control rat pancreas. The feeding of high fat diet without cholesterol, or high cholesterol diet without high fat content, did not result in significant increase in pancreatic cholesterol esterase mRNA when compared to that observed in control chow-fed animals. The increase in cholesterol esterase mRNA after high fat/high cholesterol feeding paralleled the increased in pancreatic lipase mRNA. The high fat/high cholesterol-induced increase in cholesterol esterase mRNA was due to increase rate of transcription, as demonstrated by nuclear run-on assays. Additionally, in vitro incubation experiments of pancreatic lobules with [35S]methionine showed higher rates of 35S-labeled cholesterol esterase synthesis with lobules from the high fat/high cholesterol-fed animals. Taken together, these results demonstrated that high fat/high cholesterol diets increased cholesterol esterase mRNA level and enzyme biosynthesis in rat pancreas. The coordinated regulation of cholesterol esterase with another lipid digestive enzyme, the pancreatic lipase, suggested an important role for these proteins in dietary lipid absorption through the gastrointestinal tract.