Language:

Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

Cell reports (Cambridge), 2018-04, Vol.23 (4), p.1099-1111 [Peer Reviewed Journal]

2018 The Authors ;Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. ;ISSN: 2211-1247 ;EISSN: 2211-1247 ;DOI: 10.1016/j.celrep.2018.03.109 ;PMID: 29694888

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages
Author: Krishnan, Smitha ; Ding, Yufang ; Saedi, Nima ; Choi, Maria ; Sridharan, Gautham V. ; Sherr, David H. ; Yarmush, Martin L. ; Alaniz, Robert C. ; Jayaraman, Arul ; Lee, Kyongbum
Subjects: Animals ; aryl hydrocarbon receptor ; Cytokines - immunology ; Cytokines - metabolism ; Dietary Fats - pharmacology ; Fatty Acid Synthase, Type I - immunology ; Fatty Acid Synthase, Type I - metabolism ; Gastrointestinal Microbiome - immunology ; gut microbiota ; Hep G2 Cells ; Hepatocytes - immunology ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Humans ; indole-3-acetate ; Indoleacetic Acids - immunology ; Indoleacetic Acids - metabolism ; Inflammation ; Macrophages - immunology ; Macrophages - metabolism ; Male ; metabolomics ; Mice ; nonalcoholic fatty liver disease ; RAW 264.7 Cells ; Receptors, Aryl Hydrocarbon - immunology ; Receptors, Aryl Hydrocarbon - metabolism ; Sterol Regulatory Element Binding Protein 1 - immunology ; Sterol Regulatory Element Binding Protein 1 - metabolism ; Tryptamines - immunology ; Tryptamines - metabolism ; Tryptophan - immunology ; Tryptophan - metabolism
Is Part Of: Cell reports (Cambridge), 2018-04, Vol.23 (4), p.1099-1111
Description: The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors. [Display omitted] •A high-fat diet depletes the microbiota metabolites indole-3-acetate and tryptamine•Indole-3-acetate and tryptamine attenuate indicators of inflammation in macrophages•Indole-3-acetate attenuates cytokine-mediated lipogenesis in hepatocytes Dysbiosis of the intestinal microbiota is an emerging factor contributing to the progression of fatty liver disease. Krishnan et al. utilize metabolomics and biochemical assays in conjunction with animal and cell culture models to identify microbiota-dependent metabolites that engage a host receptor to affect liver inflammatory responses under lipid loading.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 2211-1247
EISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.03.109
PMID: 29694888
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
Open Access: Cell Press Free Archives
DOAJ Directory of Open Access Journals

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

2018 The Authors ;Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. ;ISSN: 2211-1247 ;EISSN: 2211-1247 ;DOI: 10.1016/j.celrep.2018.03.109 ;PMID: 29694888

Searching Remote Databases, Please Wait