title: The circadian clock influences heart performance.
abstract: Circadian clocks are believed to provide the selective advantage of anticipation, thus allowing organisms to respond efficiently to stimuli at the appropriate moment. Disrupted circadian rhythms have been found to affect a variety of basic physiological processes. However, the importance of the circadian clock in regulating heart performance remains undetermined. We hypothesized that the circadian clock plays a crucial role in heart performance through the anticipation of daily workload. Echocardiography was employed to monitor heart function and structure in mice in a noninvasive, real-time manner. In wild-type mice, both the ejection fraction (EF) and the shortening fraction (FS), two important markers of cardiac function, show diurnal variation. In addition, the amplitude of the EF and the FS enlarges in response to forced exercise in a time-dependent manner. The diurnal variations in EF and FS are altered in mice with disruptions in circadian clock genes and are significantly attenuated under an imposed light regimen. Furthermore, it shows that the overexpression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc1α) under control of the muscle creatine kinase (MCK) promoter inhibited clock gene expression in the heart and muscle and decreased the expression of peroxisome proliferator-activated receptor alpha (Pparα), metabolic genes glucose transporter (Glut4), and acetyl-coA synthetase (Acs1). Pgc1α overexpression abolished the diurnal variation of EF. We thus propose that PGC1α might play an important role in circadian-mediated, impaired cardiac function by regulating the circadian rhythm of metabolic genes.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.forename: Guangsen
authors.initials: G
authors.lastname: Shi
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xing
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Gu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Qu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D056926:CLOCK Proteins; D057906:Circadian Clocks / Q000502:physiology*; D003066:Coenzyme A Ligases / Q000096:biosynthesis; D052283:Creatine Kinase, MM Form / Q000235:genetics; D004452:Echocardiography; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D006321:Heart / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D047493:PPAR alpha / Q000096:biosynthesis / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors
chemical_list: D051275:Glucose Transporter Type 4; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C495693:Slc2a4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D056926:CLOCK Proteins; D052283:Creatine Kinase, MM Form; D003066:Coenzyme A Ligases; C101958:acetate-CoA ligase (ADP-forming)