Molecular aspects of fructose metabolism and metabolic disease

• Published in: Cell metabolism Vol. 33; no. 12; pp. 2329 - 2354
• Main Authors: Herman, Mark A., Birnbaum, Morris J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.12.2021
• Subjects: ALDOB; cardiometabolic disease; ChREBP; Diet; fructose; Fructose - metabolism; Glucose - metabolism; GLUT5; Humans; insulin resistance; KHK; lipogenesis; Liver - metabolism; Metabolic Diseases - metabolism; NAFLD; Obesity - metabolism; steatosis; TKFC; uric acid; ChREBP; NAFLD; TKFC; cardiometabolic disease; fructose; lipogenesis; ALDOB; GLUT5; steatosis; insulin resistance; uric acid; KHK
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2021.09.010

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. Excessive consumption of sugars containing fructose is a contributor to cardiometabolic disease. In this review, Herman and Birnbaum discuss the biochemistry, genetics, and physiology of fructose metabolism, consider mechanisms by which excessive fructose consumption contributes to disease, and review recent evidence regarding the potential for new therapeutic agents.