机体具有平衡脂肪吸收、代谢、储存和分泌的功能，脂稳态的维持关系到人类的多种疾病，包括心血管病、糖尿病等。细胞维持脂稳态依赖于复杂的分子网络协同作用，但是其分子机制的研究还处于起步阶段。本课题的中心分子是一种被称为Aida的蛋白，是我们在探索Axin相互作用蛋白中首先克隆的一个新基因。在前期研究中，我们建立了Aida缺失的小鼠，并发现其表现出明显的肥胖，同时呈现肝脏脂肪累积和高血糖等代谢紊乱表型。我们的初步实验数据表明，Aida这一在哺乳动物中尚未有任何功能性报道的蛋白可能参与内质网胁迫反应。结合之前我们长期研究的与Aida有相互作用的蛋白Axin参与包括葡萄糖转运、细胞自噬和细胞能量代谢调控等维持机体脂稳态的关键细胞进程的线索，我们拟进一步研究Aida是如何参与内质网胁迫反应、细胞自噬和葡萄糖转运等进程，阐明Aida及其相互作用蛋白调控体脂稳态的分子机制，并为肥胖及其相关的代谢性疾病的预防

Organisms possess extraordinary ability to maintain homeostasis of fat absorption, consumption, storage and secretion. Deregulated fat metabolism can cause a wide range of diseases, including cardiovascular diseases, obesity, and diabetes. Although we have uncovered many genes that are implicated development of obesity and have learned they participate in numerous molecular networks, it is still unclear as to how obesity occurs as a result of dysfunction of the individual genes. In the course of identifying factors that interact with Axin, we identified a novel interactor and termed it as Aida for Axin interaction partner, dorsalization associated for its morpholino-based knockdown caused dorsalization during zebrafish embryo development. Our preliminary work has shown knockout of Aida caused severe obesity in mice, along with hepatic steatosis and hyperglycemia. We also found that Aida forms complex with components of the endoplasmic reticulum unfolded protein response (ER stress response) pathway. It has been increasingly appreciated that the UPR pathway is linked to various metabolic disorders. Based on our new findings and our established former Axin work, we aim to investigate the interplay between Aida, Axin, and the UPR pathway, and the mechanisms underlying the obesity/steatosis phenotypes associated with Aida knockout, which will contribute to the overall understanding of molecular mechanism for development of obesity, insulin sensitivity and metabolism as a whole.