Sugar-Induced obesity and insulin resistance are uncoupled from shortened survival in drosophila
| العنوان: | Sugar-Induced obesity and insulin resistance are uncoupled from shortened survival in drosophila |
|---|---|
| المؤلفون: | Georgios Marinos, Joao B. Mokochinski, Matthias Laudes, Claudia Lennicke, Alec J. Vincent, Christoph Kaleta, Lucie A.G. van Leeuwen, Eliano dos Santos, Esther van Dam, Joel James, Marcela Buricova, Holger Kramer, Andrea Foley, Andre Franke, Lena Best, Helena M. Cochemé, Wolfgang Lieb |
| المصدر: | Aging (Albany NY) Cell Metabolism |
| بيانات النشر: | Bioscientifica, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Purine, obesity, Physiology, Type 2 diabetes, 0601 Biochemistry and Cell Biology, chemistry.chemical_compound, 0302 clinical medicine, Purine metabolism, Dehydration, diabetes, biology, metabolic disease, Editorial, 1101 Medical Biochemistry and Metabolomics, high-sugar diet, Drosophila, Metabolic Networks and Pathways, medicine.medical_specialty, Longevity, Article, Endocrinology & Metabolism, 03 medical and health sciences, Insulin resistance, uric acid, Diabetes mellitus, Internal medicine, medicine, Animals, Humans, Drosophila (subgenus), Sugar, Molecular Biology, Catabolism, aging, purine catabolism, Water, water imbalance, Cell Biology, biology.organism_classification, medicine.disease, Obesity, 030104 developmental biology, Endocrinology, chemistry, Purines, sugar diet, Uric acid, Insulin Resistance, Sugars, 030217 neurology & neurosurgery |
| الوصف: | Summary 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. Graphical Abstract Highlights • Sugar-induced lifespan shortening can be uncoupled from obesity and insulin resistance • A high-sugar diet induces water imbalance in adult Drosophila • High-sugar feeding shortens fly lifespan through dysregulation of purine catabolism • Dietary sugar intake in humans is associated with circulating purine levels van Dam et al. disentangle the physiological effects of high-sugar feeding on survival using adult Drosophila. They uncouple diet-induced obesity and insulin resistance from shortened lifespan by rescuing sugar-induced water imbalance. Dietary sugar is linked to kidney dysfunction and dysregulation of purine catabolism in both flies and humans, emphasizing this pathway as a promising target for potential therapeutic interventions. |
| تدمد: | 1662-4009 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21cc62493cbb7e9722fd63e484c2b621Test https://doi.org/10.1530/ey.18.12.9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....21cc62493cbb7e9722fd63e484c2b621 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16624009 |
|---|