The fructose survival hypothesis for obesity.
The fructose survival hypothesis for obesity.
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DOI：
10.1098/rstb.2022.0230
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发表时间：
2023-09-11
影响因子：
6.3
通讯作者：
Stenvinkel, Peter
中科院分区：
文献类型：
--
作者：
Johnson, Richard J.;Lanaspa, Miguel A.;Sanchez-Lozada, L. Gabriela;Tolan, Dean;Nakagawa, Takahiko;Ishimoto, Takuji;Andres-Hernando, Ana;Rodriguez-Iturbe, Bernardo;Stenvinkel, Peter
果糖生存假说提出，肥胖和新陈代谢障碍可能是由于过度刺激了一种基于进化的生物反应(生存开关)而发展起来的，这种生物反应的目的是在危机之前保护动物。这种反应的特点是饥饿、口渴、觅食、体重增加、脂肪堆积、胰岛素抵抗、全身炎症和血压升高。这个过程是通过摄取果糖或通过多元醇途径刺激内源果糖产生而启动的。与其他营养素不同的是，果糖减少了细胞中的活跃能量(三磷酸腺苷)，同时阻止了脂肪储存的再生。这是通过细胞内尿酸、线粒体氧化应激、抑制AMP激酶和刺激加压素来实现的。线粒体氧化磷酸化被抑制，糖酵解被刺激。虽然这种反应的目的是温和和短暂的，但人类的反应被夸大了，因为获得了节俭基因，加上西方饮食中富含果糖或产生果糖的食物。我们认为，过度的果糖代谢不仅可以解释肥胖，还可以解释糖尿病、高血压、非酒精性脂肪性肝病、肥胖相关癌症、血管和阿尔茨海默氏症，甚至衰老的流行。此外，这一假说还统一了目前有关肥胖的假说。减少激活和/或阻断这一途径并刺激线粒体再生可能有益于健康跨度。本文是“肥胖的原因：理论、猜想和证据(第一部分)”讨论会的一部分。
The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
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影响因子：
11.4
作者：
Cantu-Medellin N;Kelley EE
通讯作者：
Kelley EE
影响因子：
4.6
作者：
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通讯作者：
Camara NO
影响因子：
13.5
作者：
Abdelmalek, Manal F.;Lazo, Mariana;Horska, Alena;Bonekamp, Susanne;Lipkin, Edward W.;Balasubramanyam, Ashok;Bantle, John P.;Johnson, Richard J.;Diehl, Anna Mae;Clark, Jeanne M.
通讯作者：
Clark, Jeanne M.
DOI：
10.1073/pnas.0809255105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Cha, Seung Hun;Wolfgang, Michael;Lane, M. Daniel
通讯作者：
Lane, M. Daniel
DOI：
10.1001/jama.2015.13134
发表时间：
2015-11-03
期刊：
JAMA
影响因子：
--
作者：
Abegglen LM;Caulin AF;Chan A;Lee K;Robinson R;Campbell MS;Kiso WK;Schmitt DL;Waddell PJ;Bhaskara S;Jensen ST;Maley CC;Schiffman JD
通讯作者：
Schiffman JD