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Papers In Press, published online ahead of print July 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700517-JLR200

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Journal of Lipid Research, Vol. 49, 1395-1408, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids^*,

Joseph B. Lockridge^*, Mary L. Sailors, David J. Durgan, Oluwaseun Egbejimi, William J. Jeong, Molly S. Bray, William C. Stanley and Martin E. Young^1,

^* University of Texas Health Science Center at Houston, Brown Foundation Institute of Molecular Medicine, Houston TX
United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Department of Pediatrics, Houston TX
Department of Medicine, University of Maryland, Baltimore MD

^* This work was supported by USDA/ARS Grants 6250-51000-044 and 6250-51000-046 to M.E.Y. and M.S.B. and by National Institutes of Health National Heart, Lung, and Blood Institute Grant HL-074259.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the forms of eight figures and three tables.

Published, JLR Papers in Press, April 2, 2008.

¹ To whom correspondence should be addressed. e-mail: meyoung{at}bcm.edu

Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggestthat distinct FA species are cardiotoxic (e.g., palmitate), while others are cardioprotective (e.g., oleate), although the molecular mechanisms mediating these observations are unclear. The purpose of the present study was to investigate the differential effects of distinct FA species (varying carbon length and degree of saturation) on adult rat cardiomyocyte (ARC) gene expression.ARCs were initialy challenged with 0.4 mM octanoate (8:0), palmitate (16:0), stearate (18:0), oleate (18:1), or linoleate (18:2) for 24 h. Microarray analysis revealed differential regulation of gene expression by the distinct FAs; the order regarding the number of genes whose expression was influenced by a specific FA was octanoate (1,188) > stearate (740) > palmitate (590) > oleate (83) > linoleate (65). In general, cardioprotective FAs (e.g., oleate) increased expression of genes promoting FA oxidation to a greater extent than cardiotoxic FAs (e.g., palmitate), whereas the latter induced markers of endoplasmic reticulum and oxidative stress. Subsequent RT-PCR analysis revealed distinct time- and concentration-dependent effects of these FA species, in a gene-specific manner. For example, stearate- and palmitate-mediated ucp3 induction tended to be transient (i.e., initial high induction, followed by subsequent repression), whereas oleate-mediated induction was sustained. These findings may provide insight into why diets high in unsaturated FAs (e.g., oleate) are cardioprotective, whereas diets rich in saturated FAs (e.g., palmitate) are not.

Supplementary key words β-oxidation • endoplasmic reticulum stress • gene expression

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