Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/80202
Title: Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals
Authors: Montagner, Alexandra
Korecka, Agata
Polizzi, Arnaud
Lippi, Yannick
Blum, Yuna
Canlet, Cécile
Tremblay-Franco, Marie
Gautier-Stein, Amandine
Burcelin, Rémy
Yen, Yi-Chun
Je, Hyunsoo Shawn
Maha, Al-Asmakh
Mithieux, Gilles
Arulampalam, Velmurugesan
Lagarrigue, Sandrine
Guillou, Hervé
Pettersson, Sven
Wahli, Walter
Keywords: Medicine
Issue Date: 2016
Source: 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., Maha, A. A., Mithieux, G., Arulampalam, V., Lagarrigue, S., Guillou, H., Pettersson, S., & Wahli, W. (2016). Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Scientific Reports, 6, 20127-.
Series/Report no.: Scientific Reports
Abstract: 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.
URI: https://hdl.handle.net/10356/80202
http://hdl.handle.net/10220/40393
ISSN: 2045-2322
DOI: 10.1038/srep20127
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Fulltext Permission: open
Fulltext Availability: With Fulltext
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