Drosophila melanogaster body fat regulation by store-operated calcium entry

果蝇体内脂肪通过钙库控制的进入调节

• 批准号: 240570765
• 负责人: Professor Dr. Ronald P. Kühnlein
• 金额: --
• 依托单位: Institut für Molekulare Biowissenschaften
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/240570765?language=en
• 关键词: Drosophila; melanogaster; body; fat; regulation

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.

脂质代谢稳态是动物有机体的基本和普遍特性。这种体内平衡的失调会导致严重的身体脂肪储存障碍，例如果蝇和人类等多种生物体的肥胖。可以说，遗传易感人群中不健康的生活方式改变推动了最近的人类肥胖流行。然而，对导致生物体肥胖的遗传结构的理解尚不全面。我们最近利用果蝇模型生物首次揭示了控制钙库操纵的钙进入（SOCE）的基因的错误调节通过迄今为止未知的机制导致果蝇严重肥胖。该项目提出了 SOCE 核心成分基质相互作用分子的功能表征，以确定 SOCE 依赖性体脂肪调节的生理、细胞生物学和分子基础。该项目不仅将提供关于脂质储存组织中的钙信号如何有助于果蝇体内脂肪控制的重要见解。由于 SOCE 在果蝇和人类之间进化上是保守的，因此该项目的资助有望为人类肥胖症提供新的诊断和治疗视角。