title: Period-independent novel circadian oscillators revealed by timed exercise and palatable meals.
abstract: The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle, and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple mutant mice, resulting in arrhythmic behavior in constant conditions. We uncovered rhythmic behavior in this mutant by simply exposing the mice to timed access to a palatable meal or running wheel. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues. Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. Entrainment of these novel oscillators by palatable snacks and timed exercise could become novel therapeutics for human conditions caused by disruptions of the circadian clocks.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9111 USA.|Institute of Biosciences, University of São Paulo, Rua do Matao - Travessa 14, 321, São Paulo, SP, 05508-900, Brazil.
authors.forename: Danilo E F L
authors.initials: DE
authors.lastname: Flôres
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9111 USA.
authors.forename: Crystal N
authors.initials: CN
authors.lastname: Bettilyon
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9111 USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D057906:Circadian Clocks / Q000187:drug effects / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D004435:Eating / Q000502:physiology; D005260:Female; D005502:Food; D005786:Gene Expression Regulation; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074241:Peanut Oil; D056950:Period Circadian Proteins / Q000172:deficiency / Q000235:genetics*; D017440:Photoperiod; D010805:Physical Conditioning, Animal; D010938:Plant Oils / Q000008:administration & dosage*; D012420:Running; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D000074241:Peanut Oil; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D010938:Plant Oils; D056926:CLOCK Proteins