Gene-Diet Interactions: Dietary Rescue of Metabolic Effects in spen -Depleted Drosophila melanogaster

• Published in: Genetics (Austin) Vol. 214; no. 4; pp. 961 - 975
• Main Authors: Gillette, Claire M, Hazegh, Kelsey E, Nemkov, Travis, Stefanoni, Davide, D'Alessandro, Angelo, Taliaferro, J Matthew, Reis, Tânia
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.04.2020
• Subjects: Adipose tissue; Animals; Carbohydrates; Catabolism; Corn syrup; Data analysis; Defects; Depletion; Developmental stages; Diet; Dietary Carbohydrates - metabolism; Drosophila melanogaster; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Energy balance; Epidemics; Fat Body - metabolism; Fatty acids; Gene-Environment Interaction; Genetics; Genotype & phenotype; Genotypes; Glycolysis; High fat diet; Homeodomain Proteins - genetics; Insects; Investigations; Larva - growth & development; Larva - metabolism; Lipid Metabolism; Lipids; Metabolic syndrome; Metabolome; Mutation; Nutrients; Obesity; Physiology; Proteins; RNA-Binding Proteins - genetics; Software; Yeast; Yeasts; gene–diet interaction; Spen; metabolism; Drosophila melanogaster; fat body
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1534/genetics.119.303015

Obesity and its comorbidities are a growing health epidemic. Interactions between genetic background, the environment, and behavior ( , diet) greatly influence organismal energy balance. Previously, we described obesogenic mutations in the gene (Spen) in , and roles for Spen in fat storage and metabolic state. Lipid catabolism is impaired in -deficient fat storage cells, accompanied by a compensatory increase in glycolytic flux and protein catabolism. Here, we investigate gene-diet interactions to determine if diets supplemented with specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We show that a high-yeast diet partially rescues adiposity and developmental defects. High sugar partially improves developmental timing as well as longevity of mated females. Gene-diet interactions were heavily influenced by developmental-stage-specific organismal needs: extra yeast provides benefits early in development (larval stages) but becomes detrimental in adulthood. High sugar confers benefits to Spen-depleted animals at both larval and adult stages, with the caveat of increased adiposity. A high-fat diet is detrimental according to all tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic responses to supplemented diets, diet was the dominant factor in directing the whole-organism steady-state metabolome. Obesity is a complex disease of genetic, environmental, and behavioral inputs. Our results show that diet customization can ameliorate metabolic dysfunction underpinned by a genetic factor.