Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines.
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| 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.
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| 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 |
| Journal | The Journal of clinical investigation (J Clin Invest) Vol. 131 Issue 1 (01 04 2021) ISSN: 1558-8238 [Electronic] United States |
| PMID | 33141762 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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