title: Rev-erbα in the brain is essential for circadian food entrainment.
abstract: Foraging is costly in terms of time and energy. An endogenous food-entrainable system allows anticipation of predictable changes of food resources in nature. Yet the molecular mechanism that controls food anticipation in mammals remains elusive. Here we report that deletion of the clock component Rev-erbα impairs food entrainment in mice. Rev-erbα global knockout (GKO) mice subjected to restricted feeding showed reduced elevations of locomotor activity and body temperature prior to mealtime, regardless of the lighting conditions. The failure to properly anticipate food arrival was accompanied by a lack of phase-adjustment to mealtime of the clock protein PERIOD2 in the cerebellum, and by diminished expression of phosphorylated ERK 1/2 (p-ERK) during mealtime in the mediobasal hypothalamus and cerebellum. Furthermore, brain-specific knockout (BKO) mice for Rev-erbα display a defective suprachiasmatic clock, as evidenced by blunted daily activity under a light-dark cycle, altered free-running rhythm in constant darkness and impaired clock gene expression. Notably, brain deletion of Rev-erbα totally prevented food-anticipatory behaviour and thermogenesis. In response to restricted feeding, brain deletion of Rev-erbα impaired changes in clock gene expression in the hippocampus and cerebellum, but not in the liver. Our findings indicate that Rev-erbα is required for neural network-based prediction of food availability.
authors.affiliation: Regulation of circadian clocks team, Institute of Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique, University of Strasbourg, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Delezie
authors.affiliation: Regulation of circadian clocks team, Institute of Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique, University of Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dumont
authors.affiliation: Regulation of circadian clocks team, Institute of Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique, University of Strasbourg, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sandu
authors.affiliation: Chronobiotron, UMS3415, CNRS, University of Strasbourg, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Reibel
authors.affiliation: Regulation of circadian clocks team, Institute of Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique, University of Strasbourg, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pevet
authors.affiliation: Regulation of circadian clocks team, Institute of Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique, University of Strasbourg, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological; D001831:Body Temperature; D001921:Brain / Q000378:metabolism*; D002940:Circadian Rhythm; D005247:Feeding Behavior; D008124:Locomotion; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D017440:Photoperiod
chemical_list: C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3