Dietary fructose improves intestinal cell survival and nutrient absorption Journal Article
| Authors: | Taylor, S. R.; Ramsamooj, S.; Liang, R. J.; Katti, A.; Pozovskiy, R.; Vasan, N.; Hwang, S. K.; Nahiyaan, N.; Francoeur, N. J.; Schatoff, E. M.; Johnson, J. L.; Shah, M. A.; Dannenberg, A. J.; Sebra, R. P.; Dow, L. E.; Cantley, L. C.; Rhee, K. Y.; Goncalves, M. D. |
| Article Title: | Dietary fructose improves intestinal cell survival and nutrient absorption |
| Abstract: | Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally1,2. Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell3,4. Although this pathway has been implicated in obesity and tumour promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Here we show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival5–7. Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumour growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumour growth by high-fructose corn syrup. © 2021, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | adult; controlled study; human tissue; mortality; nonhuman; animal cell; mouse; metabolism; animal tissue; cell survival; enzyme inhibition; morbidity; animal experiment; animal model; cohort analysis; obesity; enzyme activation; pathology; tumor growth; tumor; nutrient; intestine cell; cell elongation; metabolite; growth; lipid diet; absorption; surface area; western diet; length; intestine villus; pyruvate kinase; hypoxic cell; cell component; human; male; female; article; intestine absorption; fructose metabolism; fructose intake; ketohexokinase; corn syrup; fructose 1 phosphate; lipid absorption |
| Journal Title: | Nature |
| Volume: | 597 |
| Issue: | 7875 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-09-09 |
| Start Page: | 263 |
| End Page: | 267 |
| Language: | English |
| DOI: | 10.1038/s41586-021-03827-2 |
| PUBMED: | 34408323 |
| PROVIDER: | scopus |
| PMCID: | PMC8686685 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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