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糖诱导的肥胖和胰岛素抵抗与果蝇寿命缩短无关
2020-03-23 13:51

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。

高糖饮食会导致口渴、肥胖和代谢异常,从而导致包括2型糖尿病在内疾病以及寿命缩短。然而,肥胖和水失衡对健康和生存的影响是复杂的。
 
研究人员表明,高糖会导致果蝇成年期脱水,补充水分可以充分挽救它们的寿命。相反,代谢缺陷与水无关,这表明糖诱导的肥胖与体内胰岛素抵抗(且寿命减少)之间无关。
 
高糖饮食可促进尿酸(嘌呤分解代谢的最终产物)的积累,以及肾结石的形成,肾结石的形成会因脱水和生理酸化而加剧。重要的是,调节尿酸的产生以水依赖的方式影响寿命。
 
此外,在人类队列中的代谢组学分析表明,饮食中糖的摄入强烈地预测了嘌呤的循环水平。这一模型解释了独立于肥胖和胰岛素抵抗的高糖饮食的病理生理学,并强调了嘌呤代谢是延长寿命的靶标。
 
附:英文原文

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

Issue&Volume: 2020-03-19

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.

DOI: 10.1016/j.cmet.2020.02.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30075-9

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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