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AuthorMontagner, Alexandra
AuthorKorecka, Agata
AuthorPolizzi, Arnaud
AuthorLippi, Yannick
AuthorBlum, Yuna
AuthorCanlet, Cécile
AuthorTremblay-Franco, Marie
AuthorGautier-Stein, Amandine
AuthorBurcelin, Rémy
AuthorYen, Yi-Chun
AuthorJe, Hyunsoo Shawn
AuthorAl-Asmakh, Maha
AuthorMithieux, Gilles
AuthorArulampalam, Velmurugesan
AuthorLagarrigue, Sandrine
AuthorGuillou, Hervé
AuthorPettersson, Sven
AuthorWahli, Walter
Available date2016-11-01T08:00:33Z
Publication Date2016-02-16
Publication NameScientific Reports
Identifierhttp://dx.doi.org/10.1038/srep20127
CitationMontagner, A. et al. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Sci. Rep. 6, 20127
URIhttp://hdl.handle.net/10576/4943
AbstractThe 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.
SponsorRégion Midi-Pyrénées to HG (Mathusalem) and to WW (Chaire d’Excellence Pierre de Fermat). This work was also supported by grants from the Swiss National Science Foundation (individual grants to WW), the Bonizzi-Theler-Stiftung (WW), the 7th EU program TORNADO (WW, SP), and by the Etat de Vaud and the Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grants. SP is also supported by grants from the Merieux Foundation, Swedish Medical Research Council, the SCELCE Microbiome Centre at NTU, Singapore, and CIFAR Institute, Canada.
Languageen
PublisherNature Publishing Group
SubjectMicrobiology
Genetics
Cell biology
TitleHepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals
TypeArticle
Volume Number6
ESSN2045-2322
dc.accessType Open Access


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