Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus.
In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.
Damiola
F
F
Département de Biologie Moléculaire, Sciences II, Université de Genève, CH-1211 Geneva, Switzerland.
Le Minh
N
N
Preitner
N
N
Kornmann
B
B
Fleury-Olela
F
F
Schibler
U
U
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001683:Biological Clocks / Q000502:physiology*; D001831:Body Temperature; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D005247:Feeding Behavior; D005420:Flavoproteins / Q000235:genetics; D005502:Food; D005508:Food Deprivation; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D011506:Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; C498262:Nr1d1 protein, mouse; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C119828:cry protein, Drosophila; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6