Editors' ChoiceMetabolic Disease

Tracing the fate of fructose

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Science Translational Medicine  07 Mar 2018:
Vol. 10, Issue 431, eaas8965
DOI: 10.1126/scitranslmed.aas8965


The small intestine may shield the liver from the damaging effects of fructose.

Fructose is the sweetest of all naturally occurring sugars, and it has been increasingly added to foods and beverages to improve their palatability. It has been widely assumed that the majority of dietary fructose is metabolized by the liver, given its major role in metabolic processing and its high expression of the enzymes required for fructose metabolism. In a recent study, Jang et al. challenge these assumptions about fructose metabolism by showing that the small intestine—and not the liver—metabolizes the majority of dietary fructose into glucose and organic acids.

Using isotope tracing methods to track the fate of glucose and fructose carbons in mice, these studies show that the small intestine metabolizes almost 90% of dietary fructose when it is consumed at moderate doses. It is only when fructose is consumed at higher doses that the intestinal clearance of dietary fructose becomes overwhelmed, and consequently, the excess fructose is digested by the liver and the microbiota residing in the colon. These findings led the researchers to propose a new model of fructose metabolism in which the small intestine protects the liver from the harmful effects of fructose.

The researchers also showed that the intestinal capacity for fructose metabolism was improved if the mice consumed fructose for several days before the isotope studies. Moreover, the intestinal metabolism of fructose was enhanced when mice consumed fructose in the fed state rather than a fasted state. These findings suggest that consuming high amounts of fructose on an empty stomach results in decreased fructose metabolism by the intestine and greater fructose spillover to the liver.

Future work is needed to translate these findings from mice into human studies. Given that excessive fructose consumption is linked to metabolic disorders, including obesity, type 2 diabetes, and fatty liver disease, it is of critical importance to understand how dietary fructose is processed and how the body may protect itself from the damaging effects of fructose.

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