心肌细胞脂质沉积是心力衰竭常见的病理表现。我们前期证实：载脂蛋白AV（apoAV）可减少心肌细胞对游离脂肪酸（FFA）的摄取，改善脂质沉积，并下调乳脂球表皮生长因子8的表达（Mfge8）。最近研究发现，Mfge8可通过增加FFA摄取导致心肌细胞脂质沉积。Mfge8这一作用可能通过调控过氧化物酶体增值物激活受体γ（PPARγ）-PI3k/Akt途径，增加FFA摄取相关蛋白表达实现。由此推测：ApoAV可能通过抑制Mfge8的表达，影响PPARγ-PI3k/Akt途径及其下游信号通路，减少心肌细胞对FFA的摄取，改善脂质沉积。本项目拟从分子、细胞和动物水平观察apoAV对心肌细胞FFA摄取及Mfge8-PPARγ-PI3k/Akt信号通路的影响、鉴定apoAV发挥作用的关键结构，来明确apoAV调控心肌细胞FFA摄取的机制。本项目将扩展对apoAV的认识，并为肥胖人群心力衰竭的防治提供新思路。

Cardiac lipid accumulation is a major pathological manifestation of heart failure. We observed that apolipoprotein AV(apoAV) significantly reduce the cellular uptake of free fatty acid (FFA) and lipid accumulation in cardiomyocytes. Moreover, apoAV could significantly decrease the expression of milk fat globule epidermal growth factor 8(Mfge8), which has been demonstrated that could induce lipid accumulation in cardiomyocytes by promoting the cellular uptake of FFA. The effects of Mfge8 to induce lipid accumulation may relate to inhibition of the expression of FFA transported protein through peroxisome proliferators-activated receptor γ-PI3k/Akt signaling pathway. Therefore, we hypothesized apoAV may reduce lipid accumulation in cardiomyocytes by regulating the PPARγ-PI3k/Akt signaling through suppression of Mfge8 expression. In this study, we will focus to examine the effect of apoAV on the Mfge8-PPARγ-PI3k/Akt signaling pathway and identify the functional region of apoAV, in order to verify the mechanism by which apoAV regulates the cellular uptake of FFA in cardiomyocytes with lipid accumulation. This study is expected to provide a new strategy for controlling obesity-induced cardiac steatosis and congestive heart failure.