The beneficial role of vaspin in metabolic syndrome by amelioration of ER stress

为了研究vaspin的作用，我们建立了vaspin转基因（Tg）小鼠和vaspin敲除（KO）小鼠。高脂高糖饮食对Tg小鼠的肥胖、胰岛素抵抗和脂肪肝均有改善作用，而对KO小鼠则有加重作用。我们发现GRP78是一个血管蛋白相互作用的分子，GRP78与质膜上的锚定蛋白形成复合物。在肝细胞中，vaspin与GRP78/MTJ-1复合物相互作用，增强Akt和AMPK的磷酸化，改善糖脂代谢。接下来，我们研究了血管素在动脉粥样硬化中的作用。Vaspin抑制球囊损伤血管和袖带损伤血管的动脉内膜增厚。Vaspin与血管内皮细胞上的GRP78/VDAC复合物结合，并与已知的VDAC配体kringle 5竞争。Vaspin抑制kringle 5诱导的凋亡通路，增强Akt磷酸化。随后，vaspin抑制血管内皮细胞凋亡。

To study the role of vaspin, we generated vaspin transgenic (Tg) mice and vaspin knockout (KO) mice. Under high fat-high sucrose diet, the obesity, insulin resistance and fatty liver were ameliorated in Tg mice, while they were exacerbated in KO mice. We identified GRP78 as a vaspin-interacting molecule, and GRP78 forms complex with anchor proteins on the plasma membrane. On hepatocytes, vaspin interacts with GRP78/MTJ-1 complex and enhance the phosphorylation of Akt and AMPK, and improves glucose and lipid metabolism. Next, we studied the role of vaspin on atherosclerosis. Vaspin inhibited arterial intimal thickening of balloon injured and cuff-injured vessels of rodent model. Vaspin binds to GRP78/VDAC complex on vascular endothelial cells and competes with the known VDAC ligand, kringle 5. Vaspin inhibits kringle 5-induced apoptosis pathway and enhances the phosphorylation of Akt. Subsequently, vaspin inhibits apoptosis of vascular endothelial cells.