The main site for fructose metabolism has always been assumed to be the liver owing to its importance in systemic metabolism; however, a new study conducted by Joshua Rabinowitz and colleagues challenges our current understanding of mammalian fructose metabolism. The researchers found that in mice, the small intestine, and not the liver, is responsible for converting almost all the dietary fructose to glucose and other circulating metabolites.
Rabinowitz and his team fed mice a 1:1 mixture of fructose:glucose to mimic sucrose or high-fructose corn syrup. They labelled the fructose or the glucose with carbon-13 to enable quantitative tracking of metabolism by mass spectrometry. Using this method, the researchers administered different fructose:glucose doses at different time points to determine which organ metabolizes these sugars.
“...the small intestine shields or protects the liver...”
“We were surprised to find that the small intestine metabolizes almost all dietary fructose, especially for modest doses of fructose like those found in fruit,” explains Rabinowitz. Data from the present study show that ∼90% of dietary fructose is converted into glucose and other metabolites, such as lactate and glycerate, by the small intestine before it reaches the liver. The researchers found that they could overload the metabolizing capacity of the small intestine by feeding mice a high dose of fructose. When the small intestine was saturated with fructose, increased amounts of unmetabolized fructose entered the liver and some even entered the colon, where it fed the microbiota. The researchers propose that the small intestine shields or protects the liver from fructose toxicity.
Intriguingly, when mice were fed a normal chow diet prior to receiving fructose they showed improved intestinal absorption and metabolism of fructose. Eating fructose in the fed state rather than the fasted state might be better at preventing unmetabolized fructose 'spilling over' to the liver and colon.
“Our work suggests that people should rigorously avoid eating excessive sweets and drinking sugary drinks such as soda, but also probably fruit juices, on an empty stomach” concludes Rabinowitz.
Jang, C. et al. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 27, 351–361 (2018)
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Leong, I. The small intestine — a new player in fructose metabolism. Nat Rev Endocrinol 14, 190 (2018). https://doi.org/10.1038/nrendo.2018.20