Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila.
Drosophila
aging
diabetes
high-sugar diet
obesity
purine catabolism
uric acid
water imbalance
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
19
08
2019
revised:
29
01
2020
accepted:
24
02
2020
pubmed:
21
3
2020
medline:
4
9
2021
entrez:
21
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32197072
pii: S1550-4131(20)30075-9
doi: 10.1016/j.cmet.2020.02.016
pmc: PMC7156915
pii:
doi:
Substances chimiques
Sugars
0
Water
059QF0KO0R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
710-725.e7Subventions
Organisme : Medical Research Council
ID : MC_UP_1102/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-A654-5QB90
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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