Intestinal Absorption of Dietary Cholesteryl Ester Is Decreased but Retinyl Ester Absorption Is Normal in Carboxyl Ester Lipase Knockout Mice

Abstract

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 cholesterol 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 triglycerides to provide energy for growth and development while the pancreas of the neonate matures. Other suggested roles for CEL include the direct facilitation of the intestinal absorption of free cholesterol and the modification 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, independent of the CEL genotype of the pup or nursing mother. Consistent with this was the normal absorption of triglyceride in CELKO mice. The absorption of free cholesterol was also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only about 50% of the cholesterol provided as cholesteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting that 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 lipoprotein levels to diets with increasing lipid content were similar in mice of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides.

Complexity of vitamin E metabolism

“…Digestive enzymes including pancreatic lipase, carboxyl esterase and phospholipase A, secreted into the intestinal lumen, continue the digestion of dietary lipids [52] . As vitamin E in the human diet is mostly not esterified, the importance of the lipolytic degradation in the digestion system is likely limited [46] , but the need for gastric hydrolysis of the stabilized after high-dose vitamin E intake for at least one year.…”

Carboxyl Ester Lipase Deficiency Exacerbates Dietary Lipid Absorption Abnormalities and Resistance to Diet-induced Obesity in Pancreatic Triglyceride Lipase Knockout Mice

“…Plasma samples were obtained from the animals via tail bleeding at 0, 1, 3, 6, and 9 h after delivery of the test meal. The appearance of 3 H and 14 C in plasma was measured via scintillation counting and used to determine the rate of absorption of retinyl palmitate and TAG or cholesteryl esters, respectively.…”

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.…”