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Article Dans Une Revue Scientific Reports Année : 2016

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

Alexandra Montagner
  • Fonction : Auteur
Yannick Lippi
Yuna Blum
Cécile Canlet
Marie Tremblay-Franco
Amandine Gautier-Stein
Gilles Mithieux

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 germfree (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 alpha, LXR beta) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiomesensitive 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.https://www.nature.com/articles/srep23951
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hal-01482816 , version 1 (24-04-2019)

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Alexandra Montagner, Agata Korecka, Arnaud Polizzi, Yannick Lippi, Yuna Blum, et al.. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Scientific Reports, 2016, 6 (1), pp.1-14. ⟨10.1038/srep20127⟩. ⟨hal-01482816⟩
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