Metabolomic analysis of adipose tissue in Drosophila models of human obesity

点击翻译按钮获取中文摘要

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.