Modification of gene expression in rat cardiomyocytes by linoleic and docosahexaenoic acids 1

Can J Physiol Pharmacol. 2019 Apr;97(4):320-327. doi: 10.1139/cjpp-2018-0398. Epub 2018 Nov 2.

Abstract

Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of select fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes for c-fos and c-jun, followed by upregulation of inflammatory genes for nuclear factor kappa B (NF-κB) and nuclear factor of activated T-cells (NFAT). At later stages, genes involved in hypertrophic responses, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are upregulated. Adult rat cardiomyocytes were treated with palmitic acid, a saturated fatty acid; oleic acid, a monounsaturated fatty acid; linoleic acid, a polyunsaturated fatty acid belonging to the n-6 class; and docosahexaenoic acid, a polyunsaturated fatty acid belonging to the n-3 class. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-κB, NFAT3, ANP, and BNP relative to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid may be a potent inducer of genes involved in cardiac hypertrophy, whereas docosahexaenoic acid may be protective against the cardiomyocyte hypertrophic response.

Keywords: acide docosahexaénoïque; acide linoléique; acides gras polyinsaturés; cardiac hypertrophy; docosahexaenoic acid; facteurs de transcription; gènes de l’inflammation; hypertrophie cardiaque; inflammatory genes; linoleic acid; polyunsaturated fatty acids; transcription factors.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Inflammation / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • Linoleic Acid / pharmacology*
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism*
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Docosahexaenoic Acids
  • Linoleic Acid
  • JNK Mitogen-Activated Protein Kinases