|Weng, Wei - ROCKEFELLER UNIV|
|Li, Ling - MT SINAI SCH OF MEDICINE|
|Van Bennekum, Ariette - ALLEGHENY UNIV|
|Potter, Strite - MT SINAI SCH OF MEDICINE|
|Blaner, William - COLUMBIA UNIV|
|Breslow, Jan - ROCKEFELLER UNIV|
|Fisher, Edward - MT SINAI SCH OF MEDICINE|
Submitted to: Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 25, 1998
Publication Date: N/A
Interpretive Summary: This work used genetic engineering techniques to show that a particular enzyme (called carboxyl ester lipase or CEL) secreted by the pancreas was partly involved in the digestion of a form of dietary cholesterol, but was not involved in the digestion of dietary vitamin A. This work furthers our understanding of the enzymes involved in the digestion and intestinal absorption of dietary cholesterol and vitamin A. This work will be useful to scientists and physicians interested in the factors that mediate the intestinal uptake of these two important fat soluble nutrients.
Technical Abstract: Pancreatic carboxyl ester lipase (CEL) catalyzes the hydrolysis of cholesteryl esters, retinyl esters, triglycerides, and lysophospholipids. It was thought to hydrolyze cholesteryl and retinyl esters prior to absorption in the intestine. Results from in vitro and in vivo studies, however, have suggested a number of other roles for CEL in lipid metabolism, such as the absorption of free cholesterol, the hydrolysis of dietary fat in the neonatal period to promote growth and development, and the modification of lipoproteins. CEL knockout (CELKO) mice were generated to study the functions of CEL. CEL-deficient mice were born in normal-sized litters, appeared healthy, and grew well, as were pups born to and nursed by CEL-deficient dams. CELKO mice did not show significant differences in free cholesterol absorption compared to wild type mice. Though neither CELKO nor wild type mice absorbed non-hydrolyzable cholesteryl ether, CELKO mice absorbed only about 50% of cholesterol provided as cholesteryl ester as did wild type mice. In contrast to the results for cholesteryl ester, CELKO mice absorbed the same amount of retinol provided as retinyl ester as did wild type mice, whereas, neither absorbed retinyl hexadecyl ether. These data suggested that retinyl ester hydrolysis was required for absorption and that CEL was not the responsible enzyme. Triglyceride absorption was also comparable between CELKO and wild type mice. The responses of plasma lipid and lipoprotein levels to diets with increasing lipid content were similar in CELKO and wild type mice. Overall, the data indicate CEL does function in the digestion of dietary cholesteryl ester, but that other enzymes also hydrolyze cholesteryl esters as well as retinyl esters and triglycerides.