Dietary Free and Esterified Cholesterol Absorption in Cholesterol Esterase (Bile Salt-stimulated Lipase) Gene-targeted Mice

Abstract

The involvement of pancreatic cholesterol esterase (bile salt-stimulated lipase) in cholesterol absorption through the intestine has been controversial. We have addressed this issue by using homologous recombination in embryonic stem cells to produce mice lacking a functional cholesterol esterase gene. Cholesterol esterase knockout mice and their wild type counterparts were fed a bolus dose of [3H]cholesterol and a trace amount of [beta-14C]sitosterol by gavage. The ratio of the two radiolabels excreted in the feces over a 24-h period was found to be similar in the control and cholesterol esterase-null mice. Similar results were observed when the radiolabeled sterols were supplied in an emulsion with phospholipid and triolein or in lipid vesicles with phosphatidylcholine. Cholesterol absorption results were similar between the control and cholesterol esterase-null mice regardless of whether the animals were fed a low fat diet or a high fat/high cholesterol diet. The rate of [3H]cholesterol appearance in the serum of the gene-targeted mice paralleled that observed in control animals. In contrast to these results, when experiments were performed with [3H]cholesteryl oleate instead of [3H]cholesterol, a higher amount of the 3H radiolabel was found excreted in feces and dramatically less of the radiolabel was detected in the serum of the cholesterol esterase-null mice in comparison with that detected in control animals. Serum cholesterol levels were not significantly different between control and cholesterol esterase-null mice fed either control or an atherogenic diet. These results indicate that cholesterol esterase is responsible for mediating intestinal absorption of cholesteryl esters but does not play a primary role in free cholesterol absorption.

CD36 Is Important for Chylomicron Formation and Secretion and May Mediate Cholesterol Uptake in the Proximal Intestine

“…These numbers agree well with those obtained by other investigators. 22 Food intake of WT and KO mice did not show any significant difference during this study (data not shown).…”

Modified Low Density Lipoprotein Enhances the Secretion of Bile Salt-stimulated Cholesterol Esterase by Human Monocyte-Macrophages

“…Bile salt-stimulated cholesterol esterase activity, which could be inhibited by antibodies specific for the pancreatic enzyme, was also reported to be present in human serum and in the aorta (16,17). These results suggested that bile saltstimulated cholesterol esterase may have a systemic origin and participates in systemic lipid metabolism, in addition to its role for nutrient digestion and transport in the gastrointestinal tract (43).…”

Association between a polymorphism in the carboxyl ester lipase gene and serum cholesterol profile

“…Studies of CEL knockout mice show that lack of CEL appears to have no effect on the intestinal absorption of unesterified fat. 3,4 However, the cholesteryl ester hydrolytic activity is unique to CEL in the digestive tract, and CEL has been suggested to function as a supplementary enzyme to ensure effective hydrolysis of triglycerides and phospholipids. 5 The C-terminal part of CEL consists of a unique structure with proline-rich O-glycosylated repeats of 11 amino-acid residues each.…”