Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2008
Publication Date: 7/1/2008
Citation: Lockridge, J.B., Sailors, M.L., Durgan, D.J., Egbejimi, O., Jeong, W.J., Bray, M.S., Stanley, W.C., Young, M.E. 2008. Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids. Journal of Lipid Research. 49(7):1395-1408. Interpretive Summary: This paper describes the results of an experiment in which cells taken from adult rat hearts were exposed to different kinds of fats. The cells were examined to determine which genes were stimulated by the different kinds of fats. The results showed that certain kinds of fats stimulated genes that were protective of the cells, while other types of fat stimulated genes that damaged the cells. This study was designed to help understand how different kinds of fats in the diet may cause heart disease while other types of fats are good for the heart.
Technical Abstract: Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggest that 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.