title: The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids.
abstract: Cells/organs must respond both rapidly and appropriately to increased fatty acid availability; failure to do so is associated with the development of skeletal muscle and hepatic insulin resistance, pancreatic beta-cell dysfunction, and myocardial contractile dysfunction. Here we tested the hypothesis that the intrinsic circadian clock within the cardiomyocytes of the heart allows rapid and appropriate adaptation of this organ to fatty acids by investigating the following: 1) whether circadian rhythms in fatty acid responsiveness persist in isolated adult rat cardiomyocytes, and 2) whether manipulation of the circadian clock within the heart, either through light/dark (L/D) cycle or genetic disruptions, impairs responsiveness of the heart to fasting in vivo. We report that both the intramyocellular circadian clock and diurnal variations in fatty acid responsiveness observed in the intact rat heart in vivo persist in adult rat cardiomyocytes. Reversal of the 12-h/12-h L/D cycle was associated with a re-entrainment of the circadian clock within the rat heart, which required 5-8 days for completion. Fasting rats resulted in the induction of fatty acid-responsive genes, an effect that was dramatically attenuated 2 days after L/D cycle reversal. Similarly, a targeted disruption of the circadian clock within the heart, through overexpression of a dominant negative CLOCK mutant, severely attenuated induction of myocardial fatty acid-responsive genes during fasting. These studies expose a causal relationship between the circadian clock within the cardiomyocyte with responsiveness of the heart to fatty acids and myocardial triglyceride metabolism.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Durgan
authors.forename: Nowice A
authors.initials: NA
authors.lastname: Trexler
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Egbejimi
authors.forename: Tracy A
authors.initials: TA
authors.lastname: McElfresh
authors.forename: Hee Yun
authors.initials: HY
authors.lastname: Suk
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Petterson
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Paul E
authors.initials: PE
authors.lastname: Hardin
authors.forename: Molly S
authors.initials: MS
authors.lastname: Bray
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.forename: Chi-Wing
authors.initials: CW
authors.lastname: Chow
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000502:physiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides