Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines
Sarah A. Smith, … , Hiroshi Nakagawa, Gary D. Wu
Sarah A. Smith, … , Hiroshi Nakagawa, Gary D. Wu
Published November 3, 2020
Citation Information: J Clin Invest. 2021;131(1):e133371. https://doi.org/10.1172/JCI133371.
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Research Article Gastroenterology Inflammation

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines

Abstract

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium–induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.

Authors

Sarah A. Smith, Sayaka A. Ogawa, Lillian Chau, Kelly A. Whelan, Kathryn E. Hamilton, Jie Chen, Lu Tan, Eric Z. Chen, Sue Keilbaugh, Franz Fogt, Meenakshi Bewtra, Jonathan Braun, Ramnik J. Xavier, Clary B. Clish, Barry Slaff, Aalim M. Weljie, Frederic D. Bushman, James D. Lewis, Hongzhe Li, Stephen R. Master, Michael J. Bennett, Hiroshi Nakagawa, Gary D. Wu

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Figure 4

Quantification of the fatty acid oxidation intermediates, acyl-CoAs, in the colon of mice infected with C.

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Quantification of the fatty acid oxidation intermediates, acyl-CoAs, in ...
rodentium. (A) 1H NMR quantification of SCFAs from fecal water of naive and C. rodentium–infected mice. Quantification of (B) short- and (C) long-chain acyl-CoAs extracted from the colon of naive and C. rodentium–infected mice. (D) Oleic acid oxidation quantified by tritiated water release assay in colonic explants of naive and C. rodentium–infected mice. All experiments n = 5, mean ± SEM, *P < 0.05, **P < 0.01. Representative results of at least 2 independent experiments. P values represent a 2-tailed Student’s t test and paired-sample t test.