Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines.
Fatty acid oxidation
Gastroenterology
Inflammation
Inflammatory bowel disease
Mitochondria
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
04 01 2021
04 01 2021
Historique:
received:
13
09
2019
accepted:
09
10
2020
pubmed:
4
11
2020
medline:
9
9
2021
entrez:
3
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33141762
pii: 133371
doi: 10.1172/JCI133371
pmc: PMC7773399
doi:
pii:
Substances chimiques
acylcarnitine
0
Carnitine
S7UI8SM58A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : K01 DK103953
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NIDDK NIH HHS
ID : R03 DK114463
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK100485
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK050306
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114436
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM103591
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026297
Pays : United States
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