Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila.

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ID: 100836
2020
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Abstract
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.
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van-dam2020sugarinducedcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors van Dam, Esther;van Leeuwen, Lucie A G;Dos Santos, Eliano;James, Joel;Best, Lena;Lennicke, Claudia;Vincent, Alec J;Marinos, Georgios;Foley, Andrea;Buricova, Marcela;Mokochinski, Joao B;Kramer, Holger B;Lieb, Wolfgang;Laudes, Matthias;Franke, Andre;Kaleta, Christoph;Cochemé, Helena M;
Journal cell metabolism
Year 2020
DOI
S1550-4131(20)30075-9
URL
Keywords
Diabetes obesity aging uric acid drosophila high-sugar diet purine catabolism water imbalance

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