The regulation of hepatic lipid metabolism by apolipoprotein AIV

说明(申请人提供)：载脂蛋白AIV(ApoAIV)是一种脂质结合蛋白，由小肠分泌，对饮食中的脂肪作出反应。体外证据表明，apoAIV的过度表达可能对动脉粥样硬化具有保护作用，这是因为胆固醇反向运输或血浆脂质氧化的变化。然而，目前尚不清楚apoAIV基因敲除是如何如此显著地降低血脂的。ApoAIV在脂类代谢中的这一重要作用尚不清楚。ApoAIV KO小鼠是解决这一有趣问题的一个方便和成熟的模型。基于我们在apoAIV KO小鼠中的初步数据，我们假设(1)apoAIV在调节外周组织和肝脏吸收乳糜粒的效率方面发挥了重要的生理作用；2)apoAIV在肝脏作用于影响甘油三酯和胆固醇的合成和/或分泌；以及3)循环中的apoAIV的丧失对长期喂养高脂饮食引起的高脂血症具有保护作用。

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.