权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Mechanisms of Dietary Fat Digestion by Pancreatic Lipases

胰脂肪酶消化膳食脂肪的分子机制

基本信息

批准号：
9246518
负责人：
MARK E. LOWE
金额：
$ 33.17万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9246518
关键词：
Address Adsorption Adult Binding Sites Biochemistry Birth Body Weight Cardiovascular Diseases Caring Cells Child Chronic Disease Chronically Ill Colipases Complex Critical Care Critical Illness Data Development Dietary Fats Digestion Disease Duodenum Energy-Generating Resources Enzymes Family suidae Fatty Acids Fatty acid glycerol esters Gene Frequency Glucose Goals Grant Health Human Human Milk Infant Intake Knowledge Length Life Lipase Lipids Mediating Molecular Mus Neonatal Newborn Infant Nonsense Mutation Nutrient Nutritional Support Obesity Outcome Pancreas Pancreatic enzyme Physiology Premature Infant Property Publishing Rattus Recombinants Rodent Role Site-Directed Mutagenesis Structure Substrate Specificity Surface Time Tissues Weight Gain Work absorption base bench to bedside career critically ill newborn crosslink enzyme replacement therapy improved improved outcome lipid metabolism loss of function mutation novel novel therapeutics nutrition pancreatic lipase related protein 2 premature public health relevance uptake

项目摘要

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

性状（由申请方提供）：甘油三酯脂肪酶是消化膳食脂肪、组织吸收脂肪和细胞内脂肪动员所需的普遍存在的酶。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脂肪肝中脂肪的异常储存。脂肪酶在食物脂肪消化中的作用是最重要的。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。在这个应用中，我们的目标是确定辅脂酶和胰脂肪酶相关蛋白2的分子特性（PLRP 2），这使得它们对新生儿脂肪消化至关重要。我们的中心假设是，辅脂酶和PLRP 2与脂肪球相互作用，以有效地消化人类母乳中的特定脂质。为了解决我们的假设，我们提出：1）确定辅脂酶与PTL、PLRP 2和脂质的相互作用的分子细节; 2）表征母乳中的PLRP 2底物;和3）确定人类新生儿是否需要PLRP 2来进行有效的脂肪消化和体重增加。我们的工作结果将定义colipase-PLRP 2复合物和膳食脂质之间的相互作用，PLRP 2的底物特异性以及PLIPRP 2功能缺失突变对新生儿脂肪吸收的影响。这一结果将有助于进一步了解胰脂肪酶对膳食脂肪的消化作用。重要的是，目标的完成将促进新型营养疗法的临床开发，如更有效的配方或酶替代品，这将改变早产儿和危重新生儿的护理和改善结果，

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pancreatic lipase-related protein 2 digests fats in human milk and formula in concert with gastric lipase and carboxyl ester lipase.

DOI：
10.1038/pr.2013.90
发表时间：
2013-08
期刊：
PEDIATRIC RESEARCH
影响因子：
3.6
作者：
Johnson, Karin;Ross, Leah;Miller, Rita;Xiao, Xunjun;Lowe, Mark E.
通讯作者：
Lowe, Mark E.

Porcine pancreatic lipase related protein 2 has high triglyceride lipase activity in the absence of colipase.

猪胰脂肪酶相关蛋白2在辅脂肪酶不存在的情况下具有高甘油三酯脂肪酶活性。

DOI：
10.1016/j.bbalip.2013.06.002
发表时间：
2013
期刊：
Biochimica et biophysica acta
影响因子：
0
作者：
Xiao,Xunjun;Ross,LeahE;Sevilla,WednesdayA;Wang,Yan;Lowe,MarkE
通讯作者：
Lowe,MarkE

Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles.

DOI：
10.1016/j.bbalip.2013.02.009
发表时间：
2013-06
期刊：
Biochimica et biophysica acta
影响因子：
0
作者：
Ross LE;Xiao X;Lowe ME
通讯作者：
Lowe ME

Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis.

DOI：
10.1002/hep.23589
发表时间：
2010-06
期刊：
HEPATOLOGY
影响因子：
13.5
作者：
McGuire, Brendan M.;Zupanets, Igor A.;Lowe, Mark E.;Xiao, Xunjun;Syplyviy, Vasyliy A.;Monteleone, Jon;Gargosky, Sharron;Dickinson, Klara;Martinez, Antonia;Mokhtarani, Masoud;Scharschmidt, Bruce F.
通讯作者：
Scharschmidt, Bruce F.

The β5-Loop and Lid Domain Contribute to the Substrate Specificity of Pancreatic Lipase-related Protein 2 (PNLIPRP2).

β5 环和盖子结构域有助于胰腺脂肪酶相关蛋白 2 (PNLIPRP2) 的底物特异性。