Dietary fructose improves intestinal cell survival and nutrient absorption

Samuel R. Taylor, Shakti Ramsamooj, Roger J. Liang, Alyna Katti, Rita Pozovskiy, Neil Vasan, Seo-Kyoung Hwang, Navid Nahiyaan, Nancy J. Francoeur, Emma M. Schatoff, Jared L. Johnson, Manish A. Shah, Andrew J. Dannenberg, Robert P. Sebra, Lukas E. Dow, Lewis C. Cantley, Kyu Y. Rhee and Marcus D. Goncalves ()
Additional contact information
Samuel R. Taylor: Weill Cornell Medicine
Shakti Ramsamooj: Weill Cornell Medicine
Roger J. Liang: Weill Cornell Medicine
Alyna Katti: Weill Cornell Medicine
Rita Pozovskiy: Weill Cornell Medicine
Neil Vasan: Weill Cornell Medicine
Seo-Kyoung Hwang: Weill Cornell Medicine
Navid Nahiyaan: Weill Cornell Medicine
Nancy J. Francoeur: Icahn School of Medicine at Mount Sinai
Emma M. Schatoff: Weill Cornell Medicine
Jared L. Johnson: Weill Cornell Medicine
Manish A. Shah: Weill Cornell Medicine
Andrew J. Dannenberg: Weill Cornell Medicine
Robert P. Sebra: Icahn School of Medicine at Mount Sinai
Lukas E. Dow: Weill Cornell Medicine
Lewis C. Cantley: Weill Cornell Medicine
Kyu Y. Rhee: Weill Cornell Medicine
Marcus D. Goncalves: Weill Cornell Medicine

Nature, 2021, vol. 597, issue 7875, 263-267

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03827-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:597:y:2021:i:7875:d:10.1038_s41586-021-03827-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03827-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().