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Cardiomyocyte-Specific BMAL1 Plays Critical Roles in Metabolism, Signaling, and Maintenance of Contractile Function of the Heart
Open accessAbstract
Circadian clocks are cell autonomous, transcriptionally based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are 2 transcription factors, CLOCK and BMAL1. The purpose of the present study was to reveal novel physiologic functions of BMAL1 in the heart, as well as to determine the pathologic consequences of chronic disruption of this circadian clock component. To address this goal, we generated cardiomyocyte-specific Bmal1 knockout (CBK) mice. Following validation of the CBK model, combined microarray and in silico analyses were performed, identifying 19 putative direct BMAL1 target genes, which included a number of metabolic (e.g., β-hydroxybutyrate dehydrogenase 1 [Bdh1]) and signaling (e.g., the p85α regulatory subunit of phosphatidylinositol 3-kinase [Pik3r1]) genes. Results from subsequent validation studies were consistent with regulation of Bdh1 and Pik3r1 by BMAL1, with predicted impairments in ketone body metabolism and signaling observed in CBK hearts. Furthermore, CBK hearts exhibited depressed glucose utilization, as well as a differential response to a physiologic metabolic stress (i.e., fasting). Consistent with BMAL1 influencing critical functions in the heart, echocardiographic, gravimetric, histologic, and molecular analyses revealed age-onset development of dilated cardiomyopathy in CBK mice, which was associated with a severe reduction in life span. Collectively, our studies reveal that BMAL1 influences metabolism, signaling, and contractile function of the heart.
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“For instance, Bmal1 knockout in mice causes dilated cardiomyopathy (62) and selective Bmal1 knockout in cardiomyocytes eliminates much of the rhythmic transcriptome (63), reduces stroke volume and ejection fraction, and causes heart failure and early mortality in mice (63,64).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [63]
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Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515
Real time quantitative PCR.Preprint
Heid, C., Stevens, J., Livak, K. J., & Williams, P. (1996) · Genome Research · doi:10.1101/gr.6.10.986 · Cited by 6,180
Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice
Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421
A novel method for real time quantitative RT-PCR.Preprint
Gibson, U. E., Heid, C., & Williams, P. M. (1996) · Genome Research · doi:10.1101/gr.6.10.995 · Cited by 2,090
Role of the CLOCK Protein in the Mammalian Circadian Mechanism
Gekakis, N., Staknis, D., Nguyen, H. B., Davis, F. C., Wilsbacher, L. D., King, D. P., Takahashi, J. S., & Weitz, C. J. (1998) · Science · doi:10.1126/science.280.5369.1564 · Cited by 2,035
Srere, P. A. (1969) · Methods in Enzymology · doi:10.1016/0076-6879(69)13005-0 · Cited by 2,005
Circadian integration of metabolism and energetics
Bass, J., & Takahashi, J. S. (2010) · Science · doi:10.1126/science.1195027 · Cited by 1,910
Mutagenesis and Mapping of a Mouse Gene, Clock , Essential for Circadian Behavior
Vitaterna, M. H., King, D. P., Chang, A.-M., Kornhauser, J. M., Lowrey, P. L., McDonald, J. D., Dove, W. F., Pinto, L. H., Turek, F. W., & Takahashi, J. S. (1994) · Science · doi:10.1126/science.8171325 · Cited by 1,632
Mop3 is an essential component of the master circadian pacemaker in mammals.
Bunger, M. K., Wilsbacher, L. D., Moran, S. M., Clendenin, C., Radcliffe, L. A., Hogenesch, J. B., Simon, M. C., Takahashi, J. S., & Bradfield, C. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00205-1 · Cited by 1,621
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- 10.1016/0003-2697(87)90021-2 · DOI
- Delp MD, 1991, Am J Physiol, 261, H1487
- Leighton B, 1988, Am J Physiol, 255, E41
- Richards AM, 1986, Clin Exp Hypertens A, 8, 153
Cited by
Sorted by citations
Items 201–220 of 220
Environmental and genetic influence of circadian rhythm over cardiac metabolism and disease
Orlowska, M. K. (2023) · Queensland University of Technology · doi:10.5204/thesis.eprints.246041
Women in Cardiovascular Genetics and Systems Medicine
(2024) · Frontiers research topics · doi:10.3389/978-2-8325-4796-0
Circadian clock genes perform dual roles as systemic oscillators and context-dependent regulators
Takahashi, N., & Endo, M. (2025) · Development · doi:10.1242/dev.204841
Jiang, Y., Gu, Y., Xu, H., Tian, X., Zhang, X., Xu, X., Yan, W., & Zhang, X. (2020) · Figshare · doi:10.6084/m9.figshare.12519047
Ma, J., Ma, N., Zhang, L., Xu, L., Liu, X., & Meng, G. (2024) · Figshare · doi:10.6084/m9.figshare.26103813
Yu, L., Ren, L., & Dong, L. (2022) · Figshare · doi:10.6084/m9.figshare.20552359
Ma, J., Ma, N., Zhang, L., Xu, L., Liu, X., & Meng, G. (2024) · Figshare · doi:10.6084/m9.figshare.26738640
Ma, J., Ma, N., Zhang, L., Xu, L., Liu, X., & Meng, G. (2024) · Figshare · doi:10.6084/m9.figshare.26738643
Ma, J., Ma, N., Zhang, L., Xu, L., Liu, X., & Meng, G. (2024) · Figshare · doi:10.6084/m9.figshare.26103953
Rôle du facteur de transcription Bcl11b dans l’homéostasie et le remodelage cardiaque
Daher, M. (2019) · theses.fr (ABES) · doi:10.70675/bdcede14z3bf1z4c2ez937czbcf99935b333
Mélone, M.-A. (2024) · theses.fr (ABES) · doi:10.70675/443e8c4fz712bz4232za67czb9fe970a0eeb
Insomnia-Associated Circadian and Thrombotic Alterations Coincide with Morning Cardiac Vulnerability
Kumar, N., Siddiqui, M. A., & Krishnamurthy, S. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00752
Time matters: BMAL1 and cardiovascular-kidney-metabolic health
Reynolds, L. D., Guan, Z., & Pollock, J. S. (2026) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00041.2026
Type 1 diabetes differentially disrupts right and left ventricular daily rhythms
Bettadapura, S. S., Torres, S. J., Schmitt, M. P., Roberts, B. L., & Bruns, D. R. (2026) · Function · doi:10.1152/function.041.2026
Cai, Y., Qin, Y., Zhu, M., Cheng, X., Liu, Y., & Liu, Y. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156781
Deb, D., Ray, S., Sharma, P., Sharma, P., & Sikder, K. (2026) · Chronobiology International · doi:10.1080/07420528.2026.2745644
Augmented cardiac growth hormone signaling in circadian-disrupted cardiomyopathy
Ibrahim, D., & Sonkar, R. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1982446
Data from: ZeitZeiger: supervised learning for high-dimensional data from an oscillatory system
Hughey, J., Hastie, T. J., & Butte, A. J. (2016) · Data Archiving and Networked Services (DANS) · doi:10.5061/dryad.hn8gp.1
Circadian Clock Desynchrony and Cardiovascular Disease Vulnerability in Women
Crandall, M., Rabinovich-Nikitin, I., & Kirshenbaum, L. A. (2026) · Current Opinion in Physiology · doi:10.1016/j.cophys.2026.101005
Metadata
- Authors
- Young, M. E., Brewer, R. A., Peliciari-Garcia, R. A., Collins, H. E., He, L., Birky, T. L., Peden, B. W., Thompson, E. G., Ammons, B.-J., Bray, M. S., Chatham, J. C., Wende, A. R., Yang, Q., Chow, C.-W., Martino, T. A., & Gamble, K. L.
- Affiliations
- University of Alabama at Birmingham (US)
- Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Albert Einstein College of Medicine (US)
- University of Guelph (CA)
- Corresponding author
- Young, Martin E.
- ORCID
- Venue
- Journal of Biological Rhythms
- Publisher
- SAGE Publications
- Published
- 2014-08
- Volume
- 29
- Issue
- 4
- Pages
- 257-276
- ISSN
- 0748-7304 (ISSN-L)
- 1552-4531
- PMC
- PMC4260630
- OpenAlex
- W2080300476
- Cited by
- 220
- References
- 68
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 27 · 2023: 18 · 2022: 26 · 2021: 21 · 2020: 21 · 2019: 17 · 2018: 13 · 2017: 18 · 2016: 15 · 2015: 13 · 2014: 1
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biological Rhythms (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Alabama at Birmingham
- National Institutes of Health (5ul1rr025777-04, 5p60dk079626-05)
- National Heart, Lung, and Blood Institute (HL-074259, HL‑106199, R21HL106199, R21HL107709, HL-107709, R01HL074259, R01HL123574)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-079626, DK11015, P30DK056336, P30DK079626)
- National Institute of Neurological Disorders and Stroke (R01NS082413)
- National Center for Research Resources (UL1-RR-025777)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- Bmal1, circadian clock, cardiomyocytes, cardiomyocyte-specific knockout mice, BDH1, PIK3R1, ketone body metabolism, glucose utilization, fasting response, dilated cardiomyopathy, myocardial metabolism, direct transcriptional targets, lifespan
- MeSH terms
- Animals, Circadian Rhythm, Glucose, Heart, Ketone Bodies, Male, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Myocytes, Cardiac, Mice, ARNTL Transcription Factors, Circadian Clocks
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