title: Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.
abstract: The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high-fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism.
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, U904 INSERM, University of California Irvine, Irvine, CA, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, U904 INSERM, University of California Irvine, Irvine, CA, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Tognini
authors.affiliation: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, U904 INSERM, University of California Irvine, Irvine, CA, USA Center for Metabolic and Degenerative Diseases, Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Eckel-Mahan
authors.affiliation: Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, U904 INSERM, University of California Irvine, Irvine, CA, USA psc@uci.edu.
authors.forename: Paolo
authors.identifier: 0000-0001-7091-3954
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001786:Blood Glucose; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics; D002940:Circadian Rhythm; D016000:Cluster Analysis; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D047495:PPAR gamma
keywords: PPARγ; circadian clock; liver; microbiota