Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice

Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice

Author Peliciari-Garcia, Rodrigo Antonio Autor UNIFESP Google Scholar
Goel, Mehak Google Scholar
Aristorenas, Jonathan A. Google Scholar
Shah, Krishna Google Scholar
He, Lan Google Scholar
Yang, Qinglin Google Scholar
Shalev, Anath Google Scholar
Bailey, Shannon M. Google Scholar
Prabhu, Sumanth D. Google Scholar
Chatham, John C. Google Scholar
Gamble, Karen L. Google Scholar
Young, Martin E. Google Scholar
Abstract A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9 weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. (C) 2015 Elsevier B.V. All rights reserved.
Keywords Chronobiology
Contractile function
Gene expression
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor National Heart, Lung, and Blood Institute (NHLBI)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number NHLBI: HL106199
NHLBI: HL074259
NHLBI: HL123574
NHLBI: HL122975
FAPESP: 2012/02443-4
Date 2016
Published in Biochimica Et Biophysica Acta-Molecular And Cell Biology Of Lipids. Amsterdam, v. 1861, n. 10, p. 1579-1595, 2016.
ISSN 1388-1981 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 1579-1595
Access rights Closed access
Type Article
Web of Science ID WOS:000382346000017

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