Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice

Carboxyl ester lipase (CEL; EC 3.1.1.13) hydrolyzes cholesteryl esters and retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate cho lesterol and retinol from their esters prior to absorption in the intestine . CEL is also a major lipase in the breast milk of many mammals, including humans and mice, and is thought to participate in the processing of triglyc erides to provide energy for growth and development while the pancreas of t he neonate matures. Other suggested roles for CEL include the direct facili tation of the intestinal absorption of free cholesterol and the modificatio n of plasma lipoproteins. Mice with different CEL genotypes [wild type (WT) , knockout (CELKO), heterozygote] were generated to study the functions of CEL in a physiological system. Mice grew and developed normally, independen t of the CEL genotype of the pup or nursing mother. Consistent with this wa s the normal absorption of triglyceride in CELKO mice. The absorption of fr ee cholesterol was also not significantly different between CELKO (87 +/- 2 6%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, howe ver, CELKO mice absorbed only about 50% of the cholesterol provided as chol esteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting tha t another enzyme besides CEL can hydrolyze dietary CE in mice. Surprisingly , CELKO and WT mice absorbed similar amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was required for absorption, implying that CEL was not the responsible enzyme. The changes in plasma lipid and li poprotein levels to diets with increasing lipid content were similar in mic e of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholest eryl esters, retinyl esters, and triglycerides.