英国MRC伦敦医学科学研究所Helena M. Cochemé课题组发现，糖诱导的肥胖和胰岛素抵抗与果蝇寿命缩短无关。2020年3月19日，《细胞—代谢》在线发表了这一成果。
Title: Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila
Author: Esther van Dam, Lucie A.G. van Leeuwen, Eliano dos Santos, Joel James, Lena Best, Claudia Lennicke, Alec J. Vincent, Georgios Marinos, Andrea Foley, Marcela Buricova, Joao B. Mokochinski, Holger B. Kramer, Wolfgang Lieb, Matthias Laudes, Andre Franke, Christoph Kaleta, Helena M. Cochemé
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.