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, Martin E. Young

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1395-1408
Number of pages14
JournalJournal of lipid research
Issue number7
StatePublished - 2008
Externally publishedYes


  • Endoplasmic reticulum stress
  • Gene expression
  • β-oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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