Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.

Détails

ID Serval
serval:BIB_AA161C3CA3B6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.
Périodique
Scientific reports
Auteur(s)
Montagner A., Korecka A., Polizzi A., Lippi Y., Blum Y., Canlet C., Tremblay-Franco M., Gautier-Stein A., Burcelin R., Yen Y.C., Je H.S., Al-Asmakh M., Mithieux G., Arulampalam V., Lagarrigue S., Guillou H., Pettersson S., Wahli W.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
16/02/2016
Peer-reviewed
Oui
Volume
6
Pages
20127
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication types: Journal Article ; Research Support, Non-U.S. Gov't

Résumé
The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function.

Mots-clé
Animals, Biomarkers, Circadian Clocks/genetics, Female, Gastrointestinal Microbiome, Gastrointestinal Tract/metabolism, Gastrointestinal Tract/microbiology, Gene Expression Profiling, Gene Expression Regulation, Gluconeogenesis/genetics, Inactivation, Metabolic/genetics, Liver/metabolism, Male, Mice, Microbiota, Organ Specificity, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, Signal Transduction, Transcriptome
Pubmed
Open Access
Oui
Création de la notice
20/02/2016 16:45
Dernière modification de la notice
20/08/2019 15:14
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