Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice

Carboxyl ester lipase (bile salt-stimulated lipase) is a pancreatic enzyme capable of hydrolyzing esters of cholesterol and fat-soluble vitamins. It a lso efficiently digests triglycerides (TG) into free fatty acids and glycer ol and is abundant in the milk of humans and several other species. Sire us ed the mouse as a model to test the hypothesis that milk-derived carboxyl e ater lipase (CEL) digests milk TG and that without its activity milk lipids and their digestion intermediates can disrupt the intestinal epithelium of neonates. CEL protein and enzymatic activity were shown to be abundant in mouse milk. After 24-h administration of the CEL-specific inhibitor, WAY-12 1,751-5, the small intestines of treated and control neonates were analyzed histologically for signs of fat malabsorption and injury to their villus e pithelium. In vehicle-fed controls, TG were digested and absorbed in the du odenum and jejunum, whereas, in inhibitor-fed littermates, large intracellu lar neutral lipid droplets accumulated in enterocytes of the ileum, resulti ng in damage to the villus epithelium. Similar results were observed in neo nates nursed by CEL knockout females compared with heterozygous controls. T he results suggest that lack of CEL activity causes incomplete digestion of milk fat and lipid accumulation by enterocytes in the ileum of neonatal mi ce.