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Submitted on January 30, 2006
Accepted on March 15, 2006
defines a novel positive feedback loop in the rodent liver circadian clock
*Structure and Evolution of Nuclear Receptors, CNRS UMR 5161, IFR 128 BioSciences Lyon-Gerland, Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon cedex 07, France; ° INSERM U-371, Laboratoire Cerveau et Vision, IFR 19-UCBL, 18 avenue du Doyen Lépine, 69675 Bron, France; Université de Nice Sophia Antipolis CNRS FRE 2721 Bâtiment de Sciences Naturelles 28, Avenue Valrose 06108 Nice cedex 2 France; Center for Integrative Genomics, University of Lausanne, Genopode, CH-1015 Lausanne, Switzerland
* To whom correspondence should be addressed. E-mail: vincent.laudet{at}enslyon.fr.
Recent evidence has emerged that PPAR
, which is largely involved in lipid metabolism, can play an important role in connecting circadian biology and metabolism. In the present study, we investigated the mechanisms by which PPAR influences the pacemakers acting in the central clock located in the suprachiasmatic nucleus and in the peripheral oscillator of the liver. We demonstrate that PPAR plays a specific role in the peripheral circadian control as it is required to maintain the circadian rhythm of the master clock gene bmal1 in vivo. This regulation occurs via a direct binding of PPAR on a PPRE located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPAR gene expression. We further demonstrate that fenofibrate induces circadian rhythm of clock gene expression in cell culture and up-regulates hepatic bmal1 in vivo. Altogether, these results provide evidence for an additional regulatory feedback loop involving BMAL1 and PPAR in peripheral clocks.
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BMAL1 •
Peripheral clock •
Fibrates
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