Fructose 1-phosphate, an evolutionary signaling molecule of abundancy. (October 2022)

• Record Type: Journal Article
• Authors: Brouwers, Martijn C.G.J.
• Is Part Of: Trends in endocrinology and metabolism. Volume 33:Number 10(2022)
• Page Start: 680
• Page End: 689
• Publication Date: 2022-10
• Subjects: fructose -- evolution -- nonalcoholic fatty liver disease -- cardiovascular disease -- colorectal cancer -- polycystic ovary syndrome; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2022.07.007
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Evidence is accumulating that specifically fructose exerts adverse cardiometabolic effects in humans. Recent experimental studies have shown that fructose not only serves as a substrate for, among others, intrahepatic lipid formation, but also has a signaling function. It is postulated that fructose 1-phosphate (F1-P) has evolved as a signaling molecule of abundancy that stimulates nutrient absorption, lipid storage, and reproduction. Such a role would provide an explanation for why fructose contributes to the pathogenesis of evolutionary mismatch diseases, including nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), and colorectal cancer, in the current era of nutritional abundance. It is anticipated that reducing F1-P, by either pharmacological inhibition of ketohexokinase (KHK) or societal measures, will mitigate the risk of these diseases. Highlights: Fructose not only serves as a caloric substrate; it also has a signaling function. Fructose 1-phosphate (F1-P) stimulates enterocyte survival and villus elongation. F1-P stimulates hepatic glucose disposal and consequent de novo lipogenesis, which impairs the synthesis of sex hormone-binding globulin. It is postulated that F1-P has evolved as a signaling molecule of abundancy, stimulating nutrient absorption, lipid storage, and reproduction. The signaling hypothesis contributes to our understanding why fructose increases the risk of colorectal cancer, nonalcoholic fatty liver disease, cardiovascular disease, and polycystic ovary syndrome.