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Cell Metab. 2021 Dec 07;33(12):2329-2354. doi: 10.1016/j.cmet.2021.09.010. Epub 2021 Oct 06.

Molecular aspects of fructose metabolism and metabolic disease.

Cell metabolism

Mark A Herman, Morris J Birnbaum

Affiliations

  1. Division of Endocrinology, Metabolism, and Nutrition, Duke University, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA. Electronic address: [email protected].
  2. Internal Medicine Research Unit, Pfizer, Cambridge, MA, USA. Electronic address: [email protected].

PMID: 34619074 PMCID: PMC8665132 DOI: 10.1016/j.cmet.2021.09.010

Abstract

Excessive sugar consumption is increasingly considered as a contributor to the emerging epidemics of obesity and the associated cardiometabolic disease. Sugar is added to the diet in the form of sucrose or high-fructose corn syrup, both of which comprise nearly equal amounts of glucose and fructose. The unique aspects of fructose metabolism and properties of fructose-derived metabolites allow for fructose to serve as a physiological signal of normal dietary sugar consumption. However, when fructose is consumed in excess, these unique properties may contribute to the pathogenesis of cardiometabolic disease. Here, we review the biochemistry, genetics, and physiology of fructose metabolism and consider mechanisms by which excessive fructose consumption may contribute to metabolic disease. Lastly, we consider new therapeutic options for the treatment of metabolic disease based upon this knowledge.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: ALDOB; ChREBP; GLUT5; KHK; NAFLD; TKFC; cardiometabolic disease; fructose; insulin resistance; lipogenesis; steatosis; uric acid

Conflict of interest statement

Declaration of interests M.A.H. received research support from Eli Lilly and Co. M.J.B. is an employee and shareholder of Pfizer, which holds patent US20170183328A1.

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