DIETARY INDUCTION OF PANCREATIC CHOLESTEROL ESTERASE - A REGULATORY CYCLE FOR THE INTESTINAL-ABSORPTION OF CHOLESTEROL

Atherosclerosis has a strong dietary basis without a proven molecular mechanism for cholesterol absorption. To investigate the potential rol e of pancreas in this process and its interaction with the two dietary forms of cholesterol (free and esterified), we undertook to study the role of pancreatic cholesterol esterase in cholesterol absorption. Th e results showed that (i) cholesterol esters contribute a disproportio nately high fraction of absorbed dietary cholesterol, (ii) rates of in testinal cholesterol absorption are related to pancreatic cholesterol esterase activity, (iii) mRNA specific for pancreatic cholesterol este rase is induced 15-fold by dietary sterol esters and 10-fold by free s terol, (iv) the induction of cholesterol esterase mRNA is reversible, and (v) free cholesterol transport into cultured human intestinal cell s is enhanced 300% by pancreatic cholesterol esterase. These data impl icate pancreatic cholesterol esterase as pivotal in a metabolic loop u nder positive feedback control for the absorption of dietary cholester ol, whether free or esterified.