Drosophila melanogaster body fat regulation by store-operated calcium entry

脂代谢动态平衡是动物生物体的一项基本而普遍的属性。这种动态平衡的失调会导致严重的身体脂肪储存障碍，如果蝇、苍蝇和人类等各种生物的肥胖。可以说，遗传易感人群中不健康的生活方式变化推动了最近的人类肥胖大流行。然而，对于使生物体容易肥胖的遗传结构的理解是不全面的。我们最近利用果蝇模式生物首次揭示了调控商店操作的钙进入(SOCE)的基因的错误调控导致果蝇严重肥胖的机制迄今尚不清楚。本项目提出了SOCE核心成分基质相互作用分子的功能特征，以确定SOCE依赖的体脂调节的生理、细胞生物学和分子基础。这个项目不仅将为脂肪储存组织中的钙信号如何有助于苍蝇体内脂肪控制提供重要的见解。由于SOCE在进化上在苍蝇和人类之间是保守的，拟议项目的资金有望为人类肥胖症提供新的诊断和治疗视角。

Lipid metabolism homeostasis is a fundamental and universal property of animal organisms. Misregulation of this homeostasis causes severe body fat storage disorders such as obesity in organisms as diverse as Drosophila flies and humans. Arguably, unhealthful lifestyle changes in genetically predisposed populations propel the recent human obesity pandemics. Yet the understanding of the genetic architecture, which predisposes organisms to obesity, is incomprehensive. We recently employed the Drosophila model organisms to reveal for the first time that misregulation of genes, which govern store-operated calcium entry (SOCE) causes severe obesity in flies by hitherto unknown mechanisms. This project proposes the functional characterization of the SOCE core component Stromal interaction molecule to identify the physiological, cell biological and molecular basis for SOCE-dependent body fat regulation. This project will not only provide important insights into how calcium signalling in lipid storage tissue contributes to body fat control in the fly. As SOCE is evolutionarily conserved between flies and man, funding of the proposed project promises novel diagnostic and therapeutic perspectives for human obesity.