The small intestine shields the liver from fructose-induced steatosis.

Nature Metabolism
Cholsoon JangJoshua D Rabinowitz

Abstract

Per capita fructose consumption has increased 100-fold over the last century1. Epidemiological studies suggest that excessive fructose consumption, and especially consumption of sweet drinks, is associated with hyperlipidaemia, non-alcoholic fatty liver disease, obesity and diabetes2-7. Fructose metabolism begins with its phosphorylation by the enzyme ketohexokinase (KHK), which exists in two alternatively spliced forms8. The more active isozyme, KHK-C, is expressed most strongly in the liver, but also substantially in the small intestine9,10 where it drives dietary fructose absorption and conversion into other metabolites before fructose reaches the liver11-13. It is unclear whether intestinal fructose metabolism prevents or contributes to fructose-induced lipogenesis and liver pathology. Here we show that intestinal fructose catabolism mitigates fructose-induced hepatic lipogenesis. In mice, intestine-specific KHK-C deletion increases dietary fructose transit to the liver and gut microbiota and sensitizes mice to fructose's hyperlipidaemic effects and hepatic steatosis. In contrast, intestine-specific KHK-C overexpression promotes intestinal fructose clearance and decreases fructose-induced lipogenesis. Thus, intestinal fruct...Continue Reading

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Citations

Oct 1, 2020·MSystems·Avner LeshemEran Elinav
Jul 23, 2020·Nature Metabolism·Marc Hellerstein
Dec 2, 2020·Nature Reviews. Endocrinology·Mark A Herman
Dec 22, 2020·Molecular Metabolism·Kendra K Bence, Morris J Birnbaum
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Dec 30, 2020·Biomolecules·Clémence RivesWalter Wahli
Feb 24, 2021·Nature Communications·Nicholas JonesCatherine A Thornton
Mar 6, 2021·Molecular Metabolism·Jemy A GutierrezGregory J Tesz
May 22, 2021·Experimental & Molecular Medicine·Grace ParkCholsoon Jang
Jun 3, 2021·International Journal of Molecular Sciences·Sana HibinoKoji Taniguchi
Jun 17, 2021·Nature Reviews. Endocrinology·Daniel Ferguson, Brian N Finck
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Jul 3, 2021·International Journal of Molecular Sciences·Pablo MurielErika Ramos-Tovar
Oct 8, 2021·Cell Metabolism·Mark A Herman, Morris J Birnbaum
Oct 8, 2021·Cell Metabolism·Mark A Febbraio, Michael Karin

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Methods Mentioned

BETA
transgenic
PCR
blood
Assay
ELISA
Protein Assay

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