CHARACTERIZING THADA AS THE GENETIC MODIFIER OF OBESITY

Obesity is a complex condition influenced by both genetic and environmental factors and is strongly associated with diseases like type 2 diabetes and cardiovascular disorders. While lifestyle changes are important, many individuals continue to struggle with obesity due to inherited genetic differences. Genome-wide association studies (GWAS) have identified THADA (Thyroid Adenoma Associated) as a candidate gene linked to fat storage and energy balance, but its functional role in metabolism remains poorly understood. This study used Drosophila melanogaster, a model organism with conserved metabolic pathways, to investigate how THADA influences metabolism under genetically stressed conditions. We examined two experimental models: AKHRi, which mimics disrupted glucagon-like signaling, and SIRT1i, which models impaired mitochondrial function. Larval density assay showed that overexpressing THADA reduced fat storage in both AKHRi and SIRT1i models. THADA overexpression also led to a significant reduction in triglyceride levels in the SIRT1i model, confirming its role in suppressing fat accumulation. Glucose levels were moderately but consistently elevated, suggesting enhanced glucose availability or utilization, despite not reaching conventional statistical significance. Protein concentrations showed no significant difference between groups, indicating that THADA specifically targets fat and carbohydrate metabolism without affecting overall growth or biomass. The consistent trends observed in both AKHRi and SIRT1i backgrounds support the reproducibility and metabolic specificity of THADA’s effects. These findings functionally validate THADA as a genetic modifier of energy homeostasis and highlight its potential relevance in addressing obesity and diabetes-like traits.