The regulation of hepatic lipid metabolism by apolipoprotein AIV

载脂蛋白AIV对肝脏脂质代谢的调节

基本信息

批准号：
8427341
负责人：
Alison Bloom Kohan
金额：
$ 4.63万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8427341
关键词：
ADD-1 protein Address Animal Model Animals Apolipoprotein E Apolipoproteins Atherosclerosis Attenuated Binding Proteins Biological Blood Cardiovascular Diseases Cholesterol Chronic Chylomicrons Data Diet Dietary Fats Diffuse Enzymes Fat-Restricted Diet Fatty acid glycerol esters Gene Expression Genes Hepatic High Density Lipoproteins Hyperlipidemia In Vitro Infusion procedures Intestines Knock-out Label Laboratories Lipid Binding Lipid Biochemistry Lipids Lipoproteins Liver Lymph Measures Mediating Metabolism Modeling Molecular Mus Output Peripheral Physiological Physiology Plasma Play Production Proteins Recombinants Regulation Research Role SRE-2 binding protein Scientist Serum Small Intestines Techniques Testing Tissues Very low density lipoprotein Work apolipoprotein A-IV base blood lipid experience feeding interest lipid metabolism mRNA Expression novel oxidation particle programs research study response reverse cholesterol transport tool uptake

项目摘要

DESCRIPTION (provided by applicant): Apolipoprotein AIV (apoAIV) is a lipid-binding protein that is secreted by the small intestine in response to dietary lipid. In vitro evidence suggests that over-expression of apoAIV may protect against atherosclerosis because of changes in reverse cholesterol transport or the oxidation of plasma lipids. However, it is unclear how the knock-out of apoAIV so drastically reduces blood lipids. This important role of apoAIV in lipid metabolism is as yet undefined. The apoAIV KO mouse is a convenient and well- established model for addressing this intriguing question. Based on our preliminary data in apoAIV KO mice, we hypothesize (1) that apoAIV plays an important physiological role in mediating the efficiency with which chylomicrons are taken up by the peripheral tissues and liver; 2) that apoAIV acts in the liver to impact the synthesis and/or secretion of TG and cholesterol; and 3) that loss of circulating apoAIV is protective against hyperlipidemia caused by chronic feeding of a high-fat diet.

描述（由申请人提供）：载脂蛋白AIV（apoAIV）是一种脂质结合蛋白，由小肠响应膳食脂质而分泌。体外证据表明，apoAIV 的过度表达可能会因胆固醇反向转运或血浆脂质氧化的变化而预防动脉粥样硬化。然而，目前尚不清楚apoAIV的敲除如何如此大幅度地降低血脂。 apoAIV 在脂质代谢中的重要作用尚未明确。 apoAIV KO 小鼠是解决这个有趣问题的方便且完善的模型。基于我们在 apoAIV KO 小鼠中的初步数据，我们假设 (1) apoAIV 在调节乳糜微粒被外周组织和肝脏吸收的效率方面发挥着重要的生理作用； 2) apoAIV在肝脏中作用，影响TG和胆固醇的合成和/或分泌； 3) 循环apoAIV的损失可以预防由长期高脂肪饮食喂养引起的高脂血症。