Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila

van Dam Esther; van Leeuwen Lucie A. G.; dos Santos Eliano; James Joel; Best Lena; Lennicke Claudia; Vincent Alec J.; Marinos Georgios; Foley Andrea; Buricova Marcela; Mokochinski Joao B.; Kramer Holger B.; Lieb Wolfgang; Laudes Matthias; Franke Andre; Kaleta Christoph; Cocheme Helena M.

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Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila

机译：糖诱导的肥胖症和胰岛素抵抗从果蝇缩短的存活率脱离

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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.

机译：高糖饮食导致口渴，肥胖和代谢的失调，导致疾病，包括2型糖尿病和寿命缩短。然而，肥胖和水不平衡对健康和生存的影响是复杂的并且难以解开。在这里，我们表明高糖在成人果蝇中脱水，水补充充分救出了他们的寿命。相反，代谢缺陷是与水无关的，显示糖诱导的肥胖和胰岛素抵抗之间的脱离，在体内减少存活率。高糖饮食促进尿酸的积累，嘌呤分解代谢的最终产物，肾结石的形成，通过脱水和生理酸化加重的过程。重要的是，以水依赖性方式调节对寿命的尿酸产生影响。此外，人队列中的代谢组科分析显示，膳食糖摄入强烈预测循环嘌呤水平。我们的模型解释了高糖饮食的病理生理学，独立于肥胖和胰岛素抵抗，并突出嘌呤代谢作为常用靶标。

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《Cell metabolism》 |2020年第4期|共23页
作者
van Dam Esther; van Leeuwen Lucie A. G.; dos Santos Eliano; James Joel; Best Lena; Lennicke Claudia; Vincent Alec J.; Marinos Georgios; Foley Andrea; Buricova Marcela; Mokochinski Joao B.; Kramer Holger B.; Lieb Wolfgang; Laudes Matthias; Franke Andre; Kaleta Christoph; Cocheme Helena M.;
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MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

Univ Kiel Inst Expt Med D-24105 Kiel Germany;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

Univ Kiel Inst Expt Med D-24105 Kiel Germany;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

Univ Kiel Inst Epidemiol D-24105 Kiel Germany;

Univ Hosp Schleswig Holstein Dept Internal Med 1 D-24105 Kiel Germany;

Univ Kiel Inst Clin Mol Biol D-24105 Kiel Germany;

Univ Kiel Inst Expt Med D-24105 Kiel Germany;

MRC London Inst Med Sci Du Cane Rd London W12 0NN England;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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1. Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila [J] . van Dam Esther, van Leeuwen Lucie A. G., dos Santos Eliano, Cell metabolism . 2020,第4期

机译：糖诱导的肥胖症和胰岛素抵抗从果蝇缩短的存活率脱离
2. Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats [J] . KatakamP.V.G., SnipesJ.A., SteedM.M., Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism . 2012,第5期

机译：肥胖大鼠胰岛素诱导的活性氧生成和一氧化氮合酶的解偶联是脑血管胰岛素抵抗的基础
3. Habitual shortened sleep and insulin resistance: An independent relationship in obese individuals [J] . LiuA., KushidaC.A., ReavenG.M. Metabolism: Clinical and Experimental . 2013,第11期

机译：习惯性睡眠不足和胰岛素抵抗：肥胖个体的独立关系
4. FT–IR Saliva Profiling in Patients with Obesity and Obesity–Related Insulin Resistance [C] . S.A. Pullano, M. Greco, M.G. Bianco, IEEE International Symposium on Medical Measurements and Applications . 2019

机译：肥胖患者及与肥胖相关的胰岛素抵抗患者的FT-IR唾液分析
5. Impact of Uncoupling Protein 3 Deficiency on High-Fat Diet-Induced Obesity and Insulin Resistance [D] . Lomax, Tyler M. 2020

机译：解偶联蛋白3缺乏对高脂饮食诱导肥胖和胰岛素抵抗的影响
6. Expression of human uncoupling protein-3 in Drosophila insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan [O] . Dickon M. Humphrey, Janne M. Toivonen, Maria Giannakou, -1

机译：果蝇胰岛素产生细胞中人解偶联蛋白3的表达增加胰岛素样肽（DILP）的水平并缩短寿命
7. Expression of human uncoupling protein-3 in Drosophila insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan [O] . Humphrey, Dickon M., Toivonen, Janne M., Giannakou, Maria, 2009

机译：果蝇胰岛素产生细胞中人解偶联蛋白3的表达增加胰岛素样肽（DILP）的水平并缩短寿命

Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila

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