title: Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks.
abstract: Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study.
authors.affiliation: Department of Physiology, Center for Muscle Biology, University of Kentucky Medical School, Lexington, KY 40536, USA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Wolff
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Duncan
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Esser
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D008029:Lighting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009924:Organ Culture Techniques; D056950:Period Circadian Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D001786:Blood Glucose; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins
keywords: bmal1; chronic jet lag; molecular clock; period2::luciferase; phase shift; shift work; tau