Metabolomic analysis of adipose tissue in Drosophila models of human obesity

人类肥胖果蝇模型脂肪组织的代谢组学分析

• 批准号: 2893018
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2893018
• 关键词: Metabolomic; analysis; adipose; tissue; Drosophila

This project will be looking at using human obesity-linked genes to develop Drosophila models of human obesity. These models will be used to conduct a metabolomic analysis of the pathogenesis of human obesity. The main focus of the project is to look at the differences between the development of metabolically healthy and metabolically unhealthy obesity. The difference between these two endotypes of obesity is whether or not the obesity phenotype demonstrates comorbidities with diseases such as type 2 diabetes, cardiovascular disease, cancer, etc. or not. Drosophila models will be used for this project as they have an extensive genetic toolkit which allows different functions to be tested. For example, the GAL4/UAS system can be used to control gene expression in specific tissues and the Gal80ts system can be used to temporally control gene expression.For this project, obesity-linked genes will be selected based on their connection to metabolically healthy or metabolically unhealthy obesity phenotypes, involvement in adipose tissue dysfunction or involvement in liver abnormalities related to obesity. Closely related fly orthologs of these genes will be used to study the effect of these genes on obesity phenotypes in Drosophila models of human obesity. The effect of these genes can then be assessed in the Drosophila fat body (an adipose tissue and liver-like organ in flies). Metabolomic analyses will then be conducted in order to identify and quantify the metabolites related to these candidate genes to assess which metabolic pathways are being influenced in different forms of obesity. Despite the evolutionary distance between humans and Drosophila, there are still many well-conserved pathways (including metabolic and signalling pathways) between the organisms, therefore the study of candidate obesity-linked genes in Drosophila models will provide insight into the development of adverse complications related to human obesity.

该项目将着眼于利用人类肥胖相关基因来开发人类肥胖的果蝇模型。这些模型将用于对人类肥胖的发病机制进行代谢组学分析。该项目的主要重点是研究代谢健康和代谢不健康肥胖的发展之间的差异。这两种肥胖内型之间的区别在于肥胖表型是否患有2型糖尿病、心血管疾病、癌症等疾病。该项目将使用果蝇模型，因为它们拥有广泛的遗传工具包，可以测试不同的功能。例如，GAL4/UAS系统可用于控制特定组织中的基因表达，而Gal80ts系统可用于暂时控制基因表达。对于该项目，将根据肥胖相关基因与代谢健康或健康的联系来选择肥胖相关基因。代谢不健康的肥胖表型、脂肪组织功能障碍或与肥胖相关的肝脏异常。这些基因密切相关的果蝇直向同源物将用于研究这些基因对人类肥胖果蝇模型中肥胖表型的影响。然后可以在果蝇脂肪体（果蝇的脂肪组织和肝样器官）中评估这些基因的影响。然后将进行代谢组学分析，以确定和量化与这些候选基因相关的代谢物，以评估哪些代谢途径在不同形式的肥胖中受到影响。尽管人类和果蝇之间存在进化距离，但生物体之间仍然存在许多保守的途径（包括代谢和信号途径），因此在果蝇模型中对候选肥胖相关基因的研究将有助于深入了解与肥胖相关的不良并发症的发展。导致人类肥胖。