Timed feeding of mice modulates light-entrained circadian rhythms of reticulated platelet abundance and plasma thrombopoietin and affects gene expression in megakaryocytes.
Circadian (c. 24 h) rhythms of physiology are entrained to either the environmental light-dark cycle or the timing of food intake. In the current work the hypothesis that rhythms of platelet turnover in mammals are circadian and entrained by food intake was explored in mice. Mice were entrained to 12 h light-dark cycles and given either ad libitum (AL) or restricted access (RF) to food during the light phase. Blood and megakaryocytes were then collected from mice every 4 h for 24 h. It was found that total and reticulated platelet numbers, plasma thrombopoietin (TPO) concentration and the mean size of mature megakaryocytes were circadian but not entrained by food intake. In contrast, a circadian rhythm in the expression of Arnt1 in megakaryocytes was entrained by food. Although not circadian, the expression in megakaryocytes of Nfe2, Gata1, Itga2b and Tubb1 expression was downregulated by RF, whereas Ccnd1 was not significantly affected by the feeding protocol. It is concluded that circadian rhythms of total platelet number, reticulated platelet number and plasma TPO concentration are entrained by the light-dark cycle rather than the timing of food intake. These findings imply that circadian clock gene expression regulates platelet turnover in mammals.
Hartley
Paul S
PS
Centre for Cardiovascular Science, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. p.s.hartley@ed.ac.uk
Sheward
John
J
Scholefield
Emma
E
French
Karen
K
Horn
Jacqueline M
JM
Holmes
Megan C
MC
Harmar
Anthony J
AJ
D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D005326:Fetal Proteins / Q000378:metabolism; D015870:Gene Expression; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins; D010775:Photic Stimulation; D010976:Platelet Count; D034061:Thrombopoiesis / Q000502:physiology; D013926:Thrombopoietin / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D002352:Carrier Proteins; C530105:Ccnd1 protein, mouse; D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; C418485:TACC3 protein, mouse; D014157:Transcription Factors; D014404:Tubulin; D019938:Cyclin D1; D013926:Thrombopoietin