Nuclear receptors, metabolism, and the circadian clock.
As ligand-dependent transcription factors, the nuclear receptor superfamily governs a remarkable array of rhythmic physiologic processes such as metabolism and reproduction. To provide a "molecular blueprint" for nuclear receptor function in circadian biology, we established a diurnal expression profile of all mouse nuclear receptors in critical metabolic tissues. Our finding of broad expression and tissue-specific oscillation of nuclear receptors along with their key target genes suggests that diurnal nuclear receptor expression may contribute to established rhythms in metabolic physiology and that nuclear receptors may be involved in coupling peripheral circadian clocks to divergent metabolic outputs. Conversely, nuclear receptors may serve peripheral clock input pathways, integrating signals from the light-sensing central clock in the suprachiasmatic nucleus and other environmental cues, such as nutrients and xenobiotics. Interplay between the core circadian clock and nuclear receptors may define a large-scale signaling network that links biological timing to metabolic physiology.
Yang
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Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Lamia
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Evans
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D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D000090702:Constitutive Androstane Receptor; D005938:Glucocorticoids / Q000502:physiology; D008024:Ligands; D008954:Models, Biological; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D013963:Thyroid Hormones / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014212:Tretinoin / Q000502:physiology
D000090702:Constitutive Androstane Receptor; D005938:Glucocorticoids; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013963:Thyroid Hormones; D014157:Transcription Factors; D014212:Tretinoin