Mechanisms increasing n-3 highly unsaturated fatty acids in the heart

Can J Physiol Pharmacol. 2016 Mar;94(3):309-23. doi: 10.1139/cjpp-2015-0300. Epub 2015 Sep 17.

Abstract

Due to ambiguous findings on cardiovascular benefits of systemic omega-3 fatty acid therapy, endogenous mechanisms contributing to local organ-specific concentrations of highly unsaturated fatty acids (HUFA) were examined. Using gas chromatography, 43 fatty acids were analyzed in atrial and ventricular myocardium and in pericardial fluid of male Wistar rats. To examine the endogenous fatty acid metabolism, precursors were administered into the pericardial sac. Pro- and anti-inflammatory actions were induced by talc or fenofibrate, respectively. Physical exercise and a sedentary obese state were used for increased beta-oxidation. DHA (22:6n-3) was increased in ventricular when compared with atrial myocardium (9.0 ± 2.1% vs. 4.7 ± 1.0%, p < 0.001). Intrapericardial EPA (20:5n-3) application lead to an increase of the succeeding tetracosapentaenoic acid (24:5n-3) in atrial myocardium, which is a key precursor of DHA. In contrast, proinflammatory stimulation of the n-6 HUFA pathway did not influence the n-3 metabolism. Exercise- and obesity-induced increased beta-oxidation, the finalizing step of DHA synthesis, was associated with increased ventricular DHA concentrations (6.7 ± 1.0% vs. 8.4 ± 1.2%, p < 0.01). It is concluded that the endogenous metabolism contributes markedly to myocardial HUFA concentrations. The findings are supposed to influence the efficacy of oral HUFA treatment and provide a rationale for divergent findings of previous trials on omega-3 therapy.

Keywords: DHA; EPA; acide arachidonique; acides gras hautement insaturés (AGHI); acides gras polyinsaturés (AGPI); arachidonic acid; arrhythmias; arythmie; atrial fibrillation; atrium; beta-oxidation; bêta-oxydation; contraction pariétale; course sur roue; ester d’éthyle; ethyl ester; exercice; exercise; fibrillation auriculaire; heart failure; highly unsaturated fatty acids (HUFA); inflammation péricardique; insuffisance cardiaque; omega-3 (n-3); omega-6 (n-6); oméga-3 (n-3); oméga-6 (n-6); oreillette; pericardial inflammation; pericardial treatment; pericardium; poly unsaturated fatty acids (PUFA); péricarde; traitement péricardique; ventricle; ventricule; wall stress; wheel running.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Docosahexaenoic Acids / metabolism
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-6 / metabolism
  • Fatty Acids, Unsaturated / metabolism*
  • Heart Ventricles / metabolism*
  • Male
  • Myocardium / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Docosahexaenoic Acids
  • tetracosapentaenoic acid