Molecular Mechanisms of Dietary Fat Digestion by Pancreatic Lipases

描述（由申请人提供）：甘油三酯脂肪酶是一种普遍存在的酶，用于消化膳食脂肪，将脂肪吸收到组织中以及动员细胞内的脂肪。因此，脂肪酶的作用影响能量和营养摄入、心血管疾病以及肥胖或肝纤维化中脂肪的异常储存。脂肪酶在膳食脂肪消化中最为重要。我们的长期目标是阐明胰脂肪酶消化膳食脂肪的生理和分子机制。在这个应用程序中，我们的目标是确定胶原酶和胰脂肪酶相关蛋白2的分子特性

DESCRIPTION (provided by applicant): Triglyceride lipases are ubiquitous enzymes required for the digestion of dietary fats, the uptake of fats into tissues and the mobilization of fats insde cells. Consequently, the action of lipases impacts energy and nutrient intake, cardiovascular disease, and abnormal storage of fat in obesity or in hepatosteatosis. Nowhere are lipases more important than in dietary fat digestion. Our long-term goal is to elucidate the physiology and molecular mechanisms of dietary fat digestion by pancreatic lipases. In this application, our objective is to define the molecular properties of colipase and pancreatic lipase related protein 2 (PLRP2) that make them critical for neonatal fat digestion. Our central hypothesis is that colipase and PLRP2 interact with fat globules to efficiently digest specific lipids in human mother's milk. To address our hypothesis we propose to: 1) Determine the molecular details of the interactions of colipase with PTL, PLRP2 and lipids; 2) Characterize PLRP2 substrates in mother's milk and 3) Determine if human newborns require PLRP2 for efficient fat digestion and weight gain. The outcome of our work will define the interactions between the colipase-PLRP2 complex and dietary lipids, the substrate specificity of PLRP2 and the impact of a loss-of-function mutation in PLIPRP2 on fat absorption in newborns. The results will advance knowledge of dietary fat digestion by pancreatic lipases. Importantly, completion of the Aims will facilitate the bench-to-bedside development of novel nutritional therapies such as more effective formulas or enzyme replacement that will transform care and improve outcome of premature infants and critically ill newborns and