Dietary fructose improves intestinal cell survival and nutrient absorption

Taylor, SR, Ramsamooj, S., Liang, RJ etal. Dietary fructose improves intestinal cell survival and nutrient absorption. Nature (2021). https://doi.org/10.1038/s41586-021-03827-2

Commentary

Fructose consumption is considered to be a major cause of morbidity and mortality worldwide.

It has been linked to obesity and increased incidence of cancer, and dietary fructose metabolism results in fructose accumulating at high levels in cells, where fructose, a glucose transporter type 5, is phosphorylated by ketohexokinase in the form 1-phosphate, fructose.

This pathway has been implicated in the promotion of obesity and tumors, but the exact mechanism that causes these disease states in the gut remains unclear.

In this study, we show that dietary fructose improves intestinal cell survival and increases intestinal villi length in several mouse models. Improved villi length results in increased surface area and increased nutrient absorption and obesity in mice fed a high-fat diet.

In hypoxic gut cells, pyruvate kinase M2 isoform becomes cell survival-promoting monophosphate-inhibited fructose. Genetic elimination of ketohexokinase or stimulation of pyruvate kinase prevents villi elongation and abrogates nutrient absorption and tumor growth induced by feeding mice high fructose corn syrup.

All of this makes fructose's ability to promote cell survival via allosteric metabolites an additional insight into the excess adiposity produced by the Western diet, and the supporting research findings on the promotion of tumor growth by high fructose corn syrup.