Genome wide analysis in Drosophila reveals diet by gene interactions and uncovers diet responsive genes

Genetic and environmental factors contribute to metabolic health. However, they do not act in isolation. Here, we sought to understand how diet and gene interactions influence the ability to store and utilise nutrients, a major determinant of metabolic disease. We subjected the Drosophila Genetic Reference Panel (DGRP), comprising 200 genetically divergent inbred fly strains, to diets varying in sugar, fat and protein content, and assessed starvation resistance, a proxy for an obesogenic phenotype. We discovered heterogeneity in the response to diet and a diet-dependent heritability in starvation resistance. This indicates that genetics plays a major role in governing the diet-health axis. We mapped 1,350 diet-responsive SNPs in 585 genes, validated 39 candidate genes and identified CG4607, a GLUT6/GLUT8 homolog, which was required for glucose tolerance, storage and utilization. Knock down of CG4607 led to severe carbohydrate intolerance and starvation sensitivity on a high protein diet. Overall, this study provides evidence that individuals possess optimal dietary environments based on genetic heterogeneity thus offering strong support for nutrigenomic strategies to map such interactions in humans.