@article{812b47c837164431936431a50fd223ef,
title = "The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids",
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. While it is commonly believed that the liver is the main site of fructose metabolism, Jang et al. show that it is actually the small intestine that clears most dietary fructose, and this is enhanced by feeding. High fructose doses spill over to the liver and to the colonic microbiota.",
keywords = "flux, fructose, gut, isotope tracing, metabolic disease, metabolomics, microbiome, small intestine, sucrose, sugar",
author = "Cholsoon Jang and Sheng Hui and Wenyun Lu and Cowan, {Alexis J.} and Morscher, {Raphael J.} and Gina Lee and Wei Liu and Tesz, {Gregory J.} and Birnbaum, {Morris J.} and Rabinowitz, {Joshua D.}",
note = "Funding Information: This research was supported by NIH Pioneer Award 1DP1DK113643 and Diabetes Research Center Grant P30 DK019525. C.J. is a postdoctoral fellow of the American Diabetes Association (#1-17-PDF-076). S.H. is a Merck Fellow of the Life Sciences Research Foundation. G.L. is a postdoctoral fellow of the LAM Foundation (LAM00100F01-14) and Tuberous Sclerosis Alliance (TSA-01-14). Khk knockout mice were kindly provided from the University of Leeds. We thank members of the Rabinowitz lab, Lewis Cantley, Miguel Lanaspa, Richard Johnson, Michael Neinast, Shogo Wada, and Zoltan Arany for scientific discussions. Funding Information: This research was supported by NIH Pioneer Award 1DP1DK113643 and Diabetes Research Center Grant P30 DK019525 . C.J. is a postdoctoral fellow of the American Diabetes Association (#1-17-PDF-076). S.H. is a Merck Fellow of the Life Sciences Research Foundation. G.L. is a postdoctoral fellow of the LAM Foundation (LAM00100F01-14) and Tuberous Sclerosis Alliance (TSA-01-14). Khk knockout mice were kindly provided from the University of Leeds. We thank members of the Rabinowitz lab, Lewis Cantley, Miguel Lanaspa, Richard Johnson, Michael Neinast, Shogo Wada, and Zoltan Arany for scientific discussions. Funding Information: W. Liu, G.J.T., and M.J.B. are employees of Pfizer. J.D.R. receives research funding from Pfizer and collaborates with Colorado Research Partners. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2018",
month = feb,
day = "6",
doi = "10.1016/j.cmet.2017.12.016",
language = "English (US)",
volume = "27",
pages = "351--361.e3",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}