Open Close
van Dam, E., van Leeuwen, L.A.G., Dos Santos, E., James, J., Best, L., Lennicke, C., Vincent, A.J., Marinos, G., Foley, A., Buricova, M., Mokochinski, J.B., Kramer, H.B., Lieb, W., Laudes, M., Franke, A., Kaleta, C., Cochemé, H.M. (2020). Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila.  Cell Metab. 31(4): 710--725.e7.
FlyBase ID
Publication Type
Research paper

High-sugar diets cause thirst, obesity, and metabolic dysregulation, leading to diseases including type 2 diabetes and shortened lifespan. However, the impact of obesity and water imbalance on health and survival is complex and difficult to disentangle. Here, we show that high sugar induces dehydration in adult Drosophila, and water supplementation fully rescues their lifespan. Conversely, the metabolic defects are water-independent, showing uncoupling between sugar-induced obesity and insulin resistance with reduced survival in vivo. High-sugar diets promote accumulation of uric acid, an end-product of purine catabolism, and the formation of renal stones, a process aggravated by dehydration and physiological acidification. Importantly, regulating uric acid production impacts on lifespan in a water-dependent manner. Furthermore, metabolomics analysis in a human cohort reveals that dietary sugar intake strongly predicts circulating purine levels. Our model explains the pathophysiology of high-sugar diets independently of obesity and insulin resistance and highlights purine metabolism as a pro-longevity target.

PubMed ID
PubMed Central ID
PMC7156915 (PMC) (EuropePMC)
Related Publication(s)

Sugar-induced dysregulation of purine metabolism impacts lifespan.
Lennicke et al., 2020, Aging 12(24): 24479--24480 [FBrf0247738]

Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Cell Metab.
    Cell Metabolism
    Publication Year
    Data From Reference
    Alleles (2)
    Genes (2)
    Human Disease Models (4)