Sugar-Induced obesity and insulin resistance are uncoupled from shortened survival in drosophila

In brief: High-sugar diets cause thirst, obesity and metabolic dysregulation, leading to insulin resistance, the MetS, T2DM and shortened lifespan. This study shows that high sugar diets induce dehydration in adult Drosophila. Water supplementation fully rescued the shortened lifespan, but not the metabolic defects, indicating that these are water-independent. High-sugar diets promote the accumulation of uric acid, an end-product of purine catabolism, and the formation of renal stones. These findings were confirmed in a human cohort with metabolomics and dietary data. Thus, the purine pathway is strongly involved in survival.