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，响应膳食脂质。体外证据表明，apoAIV的过度表达可能通过改变胆固醇的逆向转运或血浆脂质的氧化来预防动脉粥样硬化。然而，目前尚不清楚敲除apoAIV是如何大幅降低血脂的。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一个方便和完善的模型。根据我们在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起着重要的生理作用；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的减少对长期高脂肪饮食引起的高脂血症有保护作用。

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.