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Cell Metab. 2018 Feb 6;27(2):351-361.e3. doi: 10.1016/j.cmet.2017.12.016.

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids.

Author information

1
Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
2
Department of Pharmacology and Meyer Cancer Center, Weill Cornell Medical School, New York, NY 10065, USA.
3
Pfizer Inc. Internal Medicine, Cambridge, MA 02139, USA.
4
Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address: joshr@princeton.edu.

Abstract

Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (≥1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.

KEYWORDS:

flux; fructose; gut; isotope tracing; metabolic disease; metabolomics; microbiome; small intestine; sucrose; sugar

PMID:
29414685
PMCID:
PMC6032988
DOI:
10.1016/j.cmet.2017.12.016
[Indexed for MEDLINE]
Free PMC Article

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