Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep20127
Title: Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals
Authors: 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
Keywords: biological marker
cell receptor
transcriptome
animal
antibody specificity
circadian rhythm
drug inactivation
female
gastrointestinal tract
gene expression profiling
gene expression regulation
genetics
gluconeogenesis
intestine flora
liver
male
metabolism
microbiology
microflora
mouse
signal transduction
Animals
Biomarkers
Circadian Clocks
Female
Gastrointestinal Microbiome
Gastrointestinal Tract
Gene Expression Profiling
Gene Expression Regulation
Gluconeogenesis
Inactivation, Metabolic
Liver
Male
Mice
Microbiota
Organ Specificity
Receptors, Cytoplasmic and Nuclear
Signal Transduction
Transcriptome
Issue Date: 2016
Citation: 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. ScholarBank@NUS Repository. https://doi.org/10.1038/srep20127
Rights: Attribution 4.0 International
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 (PPAR?, LXR?) 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.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178942
ISSN: 20452322
DOI: 10.1038/srep20127
Rights: Attribution 4.0 International
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