The fructose survival hypothesis for obesity
Johnson R, Lanaspa M, Sanchez-Lozada G, Tolan D, Nakagawa T, Ishimoto T, Andres-Hernando A, Rodriguez-Iturbe B, Stenvinkel P (2023) Physiological Transactions of the Royal Society of London Sep 11;378(1885):20220230
Web URL: Read this article on PubMed
Abstract:
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)'.
FAB RESEARCH COMMENT:
For the related news article, see:See also these related research articles:
Food and Behaviour Research is a registered charity (No SC034604) and a company limited by guarantee (Co No SC 253448)
Newsletter Signup
Useful Links
Contact Us
FAB Research
23 Carlton Road
Oxford
OX2 7SA
Important Notice
Medical opinion and guidance should always be sought for any symptoms that might possibly reflect a known or suspected disease, disorder or medical condition. Information provided on this website (or by FAB Research via any other means) does not in any way constitute advice on the treatment of any medical condition formally diagnosed or otherwise.
Site by Redstone Websites. Easy to Use Web Content Management. 2025 © All Rights Reserved.