Howles P N, Stemmerman G N, Fenoglio-Preiser C M, Hui D Y
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0529, USA.
Am J Physiol. 1999 Sep;277(3):G653-61. doi: 10.1152/ajpgi.1999.277.3.G653.
Carboxyl ester lipase (bile salt-stimulated lipase) is a pancreatic enzyme capable of hydrolyzing esters of cholesterol and fat-soluble vitamins. It also efficiently digests triglycerides (TG) into free fatty acids and glycerol and is abundant in the milk of humans and several other species. We used the mouse as a model to test the hypothesis that milk-derived carboxyl ester 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-121,751-5, the small intestines of treated and control neonates were analyzed histologically for signs of fat malabsorption and injury to their villus epithelium. In vehicle-fed controls, TG were digested and absorbed in the duodenum and jejunum, whereas, in inhibitor-fed littermates, large intracellular neutral lipid droplets accumulated in enterocytes of the ileum, resulting in damage to the villus epithelium. Similar results were observed in neonates nursed by CEL knockout females compared with heterozygous controls. The results suggest that lack of CEL activity causes incomplete digestion of milk fat and lipid accumulation by enterocytes in the ileum of neonatal mice.
羧基酯脂肪酶（胆汁盐刺激脂肪酶）是一种胰腺酶，能够水解胆固醇酯和脂溶性维生素酯。它还能有效地将甘油三酯（TG）消化为游离脂肪酸和甘油，并且在人类和其他几种物种的乳汁中含量丰富。我们以小鼠为模型来验证以下假设：源自乳汁的羧基酯脂肪酶（CEL）可消化乳汁中的TG，且若无其活性，乳汁脂质及其消化中间产物会破坏新生小鼠的肠上皮。结果显示，CEL蛋白和酶活性在小鼠乳汁中含量丰富。在给新生小鼠连续24小时施用CEL特异性抑制剂WAY-121,751-5后，对处理组和对照组新生小鼠的小肠进行组织学分析，以寻找脂肪吸收不良和绒毛上皮损伤的迹象。在喂食赋形剂的对照组中，TG在十二指肠和空肠被消化和吸收，而在喂食抑制剂的同窝小鼠中，大量细胞内中性脂质滴在回肠肠细胞中积累，导致绒毛上皮受损。与杂合子对照组相比，由CEL基因敲除雌性小鼠哺育的新生小鼠也观察到了类似结果。这些结果表明，CEL活性缺乏会导致新生小鼠回肠中乳脂肪消化不完全以及肠细胞脂质蓄积。
