The regulation of hepatic lipid metabolism by apolipoprotein AIV

描述（由申请人提供）：载脂蛋白AIV（apoAIV）是一种脂质结合蛋白，由小肠分泌，以响应膳食脂质。体外研究表明，apoAIV的过度表达可能会保护动脉粥样硬化，因为胆固醇逆向转运或血浆脂质氧化的变化。然而，目前还不清楚敲除apoAIV如何如此显著地降低血脂。载脂蛋白AIV在脂质代谢中的重要作用尚未明确。apoAIV基因敲除小鼠是解决这一有趣问题的一个方便和完善的模型。基于我们在apoAIV基因敲除小鼠中的初步数据，我们假设（1）apoAIV在介导乳糜微粒被外周组织和肝脏摄取的效率中起重要的生理作用：（2）apoAIV在肝脏中作用于影响TG和胆固醇的合成和/或分泌;和3）循环apoAIV的损失对由高脂饮食的慢性喂养引起的高脂血症具有保护作用。 公共卫生相关性：载脂蛋白AIV（apoAIV）是一种脂质结合蛋白，由小肠分泌，以响应饮食脂质。敲除apoAIV可显著降低血脂水平。apoAIV在脂质代谢中的重要作用尚未明确，这是博士后提案的重点。

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. PUBLIC HEALTH RELEVANCE: Apolipoprotein AIV (apoAIV) is a lipid-binding protein that is secreted by the small intestine in response to dietary lipid. The knock-out of apoAIV drastically reduces blood lipid levels. This important role of apoAIV in lipid metabolism is as yet undefined and is the focus of the postdoctoral proposal.