Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals (vol 6, 20127, 2016)

作     者：Montagner, Alexandra Korecka, Agata Polizzi, Arnaud Lippi, Yannick Blum, Yuna Canlet, Cecile Tremblay-Franco, Marie Gautier-Stein, Amandine Burcelin, Remy Yen, Yi-Chun Je, Hyunsoo Shawn Al-Asmakh, Maha Mithieux, Gilles Arulampalam, Velmurugesan Lagarrigue, Sandrine Guillou, Herve Pettersson, Sven Wahli, Walter 

作者机构：INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institutet Stockholm Sweden INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France Department of Medicine Division of Cardiology UCLA Los Angeles USA INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France Institut National de la Santé et de la Recherche Médicale U855 Lyon France Institut des Maladies Métaboliques et Cardiovasculaires Hôpital Rangueil Toulouse Cedex France Molecular Neurophysiology Laboratory Signature Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore Singapore Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Singapore Molecular Neurophysiology Laboratory Signature Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore Singapore Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Singapore Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institutet Stockholm Sweden Department of Health Sciences College of Arts and Sciences Qatar University Daha Qatar Institut National de la Santé et de la Recherche Médicale U855 Lyon France Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institutet Stockholm Sweden INRA UMR1348 Pegase Saint-Gilles France Agrocampus Ouest UMR1348 Pegase France Rennes Université Européenne de Bretagne France INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institutet Stockholm Sweden Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore SCELSE microbiome centre Nanyang Technological University Singapore Singapore INRA ToxAlim UMR1331 Chemin de Tournefeuille Toulouse Cedex France Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore Center for Integrative Genomics University of Lausanne Le Genopode Lausanne Switzerland 

出 版 物：《SCIENTIFIC REPORTS》 (科学报告)

年 卷 期：2016年第6卷第1期

页      面：20127-20127页

核心收录：

学科分类：12[管理学] 1201[管理学-管理科学与工程(可授管理学、工学学位)] 08[工学] 

基　　金：7th EU Bonizzi-Theler-Stiftung CIFAR Institute, Canada Etat de Vaud Merieux Foundation Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF Nantong University, NTU Medicinska Forskningsrådet, MFR Lee Kong Chian School of Medicine, Nanyang Technological University, LKCMedicine 

摘      要：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.