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Sugar-induced obesity and insulin resistance are uncoupled from shortened survival in Drosophila

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Title: Sugar-induced obesity and insulin resistance are uncoupled from shortened survival in Drosophila
Authors: Van Dam, E
Van Leeuwen, LAG
Dos Santos, E
James, J
Best, L
Lennicke, C
Vincent, AJ
Marinos, G
Foley, A
Buricova, M
Mokochinski, JB
Kramer, HB
Lieb, W
Laudes, M
Franke, A
Kaleta, C
Cocheme, HM
Item Type: Journal Article
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.
Issue Date: 7-Apr-2020
Date of Acceptance: 24-Feb-2020
URI: http://hdl.handle.net/10044/1/78059
DOI: 10.1016/j.cmet.2020.02.016
ISSN: 1550-4131
Publisher: Elsevier (Cell Press)
Start Page: 710
End Page: 725
Journal / Book Title: Cell Metabolism
Volume: 31
Issue: 4
Copyright Statement: © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Drosophila
high-sugar diet
purine catabolism
uric acid
water imbalance
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Endocrinology & Metabolism
Publication Status: Published
Open Access location: https://doi.org/10.1016/j.cmet.2020.02.016
Online Publication Date: 2020-03-19
Appears in Collections:Institute of Clinical Sciences