糖可導致早期死亡，但不是由於肥胖 Sugar leads to early death, but not due to obesity

News Release 19-Mar-2020

MRC London Institute of Medical Sciences

Sugar-rich diets have a negative impact on health independent of obesity reports a new study led by the MRC London Institute of Medical Sciences, UK.

Researchers discovered that the shortened survival of fruit flies fed a sugar-rich diet is not the result of their diabetic-like metabolic issues.

The findings, published in the journal Cell Metabolism, instead suggest that early death from excess sugar is related to the build-up of a natural waste product, uric acid.

We all know that consuming too much sugar is unhealthy. It increases our risk of developing metabolic disorders, such as obesity and diabetes, and can shorten our life expectancy by several years. While this reduction in lifespan is widely believed to be caused by metabolic defects, this new study in fruit flies reveals that this may not be the case.

“Just like humans, flies fed a high-sugar diet show many hallmarks of metabolic disease – for instance, they become fat and insulin resistant”, says Dr Helena Cochemé, the principal investigator of the study. “Obesity and diabetes are known to increase mortality in humans, and so people always assumed that this was how excess sugar is damaging for survival in flies”.

However, like salt, sugar also causes dehydration. In fact, thirst is an early symptom of high blood sugar and diabetes. Dr Cochemé continues: “Water is vital for our health, yet its importance is often overlooked in metabolic studies. Therefore, we were surprised that flies fed a high-sugar diet did not show a reduced lifespan, simply by providing them with an extra source of water to drink. Unexpectedly, we found that these flies still exhibited the typical metabolic defects associated with high dietary sugar”.

Based on this water effect, the team decided to focus on the fly renal system. They showed that excess dietary sugar caused the flies to accumulate a molecule called uric acid. Uric acid is an end-product from the breakdown of purines, which are important building blocks in our DNA. But uric acid is also prone to crystallise, giving rise to kidney stones in the fly. Researchers could prevent these stones, either by diluting their formation with drinking water or by blocking the production of uric acid with a drug. In turn, this protected against the shortened survival associated with a sugar-rich diet.

So, does this mean we can eat all the sugary treats we want, as long as we drink plenty of tea? “Unfortunately not,” says Dr Cochemé, “the sugar-fed flies may live longer when we give them access to water, but they are still unhealthy. And in humans, for instance, obesity increases the risk of heart disease. But our study suggests that disruption of the purine pathway is the limiting factor for survival in high-sugar-fed flies. This means that early death by sugar is not necessarily a direct consequence of obesity itself”.

To understand the impact of dietary sugars on human health, collaborators from Kiel University in Germany explored the influence of diet in healthy volunteers. “Strikingly, just like flies, we found that dietary sugar intake in humans was associated with worse kidney function and higher purine levels in the blood”, says Prof. Christoph Kaleta, co-author of the study.

Accumulation of uric acid is a known direct cause of kidney stones in humans, as well as gout, a form of inflammatory arthritis. Uric acid levels also tend to increase with age, and can predict the onset of metabolic diseases such as diabetes. “It will be very interesting to explore how our results from the fly translate to humans, and whether the purine pathway also contributes to regulating human survival”, concludes Dr Cochemé. “There is substantial evidence that what we eat influences our life expectancy and our risk for age-related diseases. By focusing on the purine pathway, our group hopes to find new therapeutic targets and strategies that promote healthy ageing”.

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Notes to Editors

For more information or interview requests, please contact: Sophie Arthur, LMS Science Communications Officer. Tel: +44 (0)7725 159772, Email: [email protected]

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, and Helena M. Cochemé, “Sugar-Induced Obesity and Insulin Resistance Are Uncoupled from Shortened Survival in Drosophila”, will be published online in Cell Metabolism on Thursday 19th March 15:00 UK time / 11:00 US ET, and is under strict embargo until then.

The DOI for this paper will be: https://doi.org/10.1016/j.cmet.2020.02.016

The article will be published in the April 7th print issue of Cell Metabolism.

Funding

The research was funded by the Medical Research Council (MRC), with additional support by a studentship from the Commonwealth Scholarship Commission and a mobility grant from the Erasmus programme. The study also involved collaborators from Kiel University in Germany, funded by the Deutsche Forschungsgemeinschaft (DFG).

About the MRC London Institute of Medical Sciences (LMS)

The MRC London Institute of Medical Sciences (LMS) is a research institute which aims to advance the understanding of biology and its application to medicine. Our research is focused on some of the UK’s major health challenges that arise from changes in diet (obesity, diabetes and heart disease) and increased lifespan (dementia and cancer). Through tackling fundamental questions about the links between our genes, environmental stresses such as diet, and the way our bodies age researchers aim to translate this knowledge to improve the understanding, diagnosis and treatment of diverse medical conditions. Research at the institute falls into three sections: epigenetics, genes and metabolism and quantitative biology. The LMS is core funded by the Medical Research Council (MRC), which is part of UK Research and Innovation (UKRI).

http://www.lms.mrc.ac.uk | Twitter @MRC_LMS

糖可導致早期死亡，但不是由於肥胖

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糖可導致早期死亡，但不是由於肥胖

MRC倫敦醫學科學研究所
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圖像：關閉玻璃罐，裡面裝有方糖，側面有6個方糖。查看更多

圖片提供：Suzy Hazelwood通過Pexels.com

英國MRC倫敦醫學科學研究所領導的一項新研究表明，富含醣類的飲食對健康的負面影響與肥胖無關。

研究人員發現，餵食富含糖的飲食的果蠅存活時間的縮短並不是其糖尿病樣代謝問題的結果。

這項發現發表在《細胞代謝》雜誌上，相反，它表明過量糖分引起的早期死亡與天然廢物尿酸的積累有關。

我們都知道攝入過多的糖是不健康的。它增加了我們發生代謝性疾病（例如肥胖症和糖尿病）的風險，並且可能使我們的預期壽命縮短數年。儘管人們普遍認為壽命的縮短是由代謝缺陷引起的，但這項對果蠅的新研究表明並非如此。

該研究的主要研究人員海倫娜·科赫梅（HelenaCochemé）博士說：“就像人類一樣，高糖飲食的果蠅表現出許多新陳代謝疾病的特徵-例如，它們變得對脂肪和胰島素具有抵抗力。” “眾所周知，肥胖和糖尿病會增加人類的死亡率，因此人們一直認為，這就是過量糖對果蠅生存造成的損害”。

但是，糖也像鹽一樣，也會引起脫水。實際上，口渴是高血糖和糖尿病的早期症狀。 Cochemé博士繼續說道：“水對我們的健康至關重要，但是在代謝研究中水的重要性常常被忽略。因此，令我們驚訝的是，飼餵高糖飲食的果蠅沒有顯示出壽命縮短的情況，只是為它們提供了額外的來源出乎意料的是，我們發現這些果蠅仍然表現出與高飲食糖有關的典型的代謝缺陷”。

基於這種水效應，研究小組決定重點研究蠅腎系統。他們表明，過量的飲食糖會導致果蠅積聚稱為尿酸的分子。尿酸是嘌呤分解的最終產物，嘌呤是我們DNA的重要組成部分。但是尿酸也容易結晶，在飛行中會產生腎結石。研究人員可以通過用飲用水稀釋結石的形成或通過用藥物阻止尿酸的生成來預防結石。反過來，這可以防止因富含糖的飲食而導致的生存期縮短。

那麼，這是否意味著只要我們喝大量的茶，我們就可以吃所有想要的含糖食品？科赫梅博士說：“不幸的是，當我們讓食糖的蒼蠅獲得飲水時，它們的壽命可能更長，但它們仍然不健康。例如，在人類中，肥胖會增加患心髒病的風險。但是，我們的研究提示嘌呤途徑的破壞是高糖餵養果蠅存活的限制因素。這意味著糖過早死亡不一定是肥胖症本身的直接後果。”

為了了解飲食糖對人體健康的影響，德國基爾大學的合作者探討了飲食對健康志願者的影響。該研究的合著者克里斯托夫·卡萊塔教授（Christoph Kaleta）說：“驚人地，就像蒼蠅一樣，我們發現人類飲食中的糖攝入與腎臟功能惡化和血液中嘌呤水平升高有關。”

尿酸的積累是人類腎結石以及痛風（炎性關節炎的一種形式）的已知直接原因。尿酸水平也會隨著年齡的增長而增加，並且可以預測諸如糖尿病等代謝性疾病的發作。 “研究我們的飛行結果如何轉化為人類，以及嘌呤途徑是否也有助於調節人類的生存，將是非常有趣的，”Cochemé博士總結道。 “有大量證據表明，我們吃的東西會影響我們的預期壽命和與年齡有關的疾病的風險。通過研究嘌呤途徑，我們的團隊希望找到促進健康老齡化的新治療目標和策略。”