TitleThe Small Intestine Converts Dietary Fructose into Glucose and Organic Acids.
Publication TypeJournal Article
Year of Publication2018
AuthorsJang, C, Hui, S, Lu, W, Cowan, AJ, Morscher, RJ, Lee, G, Liu, W, Tesz, GJ, Birnbaum, MJ, Rabinowitz, JD
JournalCell Metab
Date Published2018 02 06
KeywordsAnimals, Carboxylic Acids, Dietary Carbohydrates, Feeding Behavior, Fructose, Glucose, Intestine, Small, Isotope Labeling, Liver, Metabolome, Mice, Inbred C57BL, Microbiota, Models, Biological

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.

Alternate JournalCell Metab.
PubMed ID29414685
PubMed Central IDPMC6032988
Grant ListDP1 DK113643 / DK / NIDDK NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States