title: Do fish oil omega-3 fatty acids enhance antioxidant capacity and mitochondrial fatty acid oxidation in human atrial myocardium via PPARγ activation?
abstract: Abstract Studies in experimental models suggest that n-3 polyunsaturated fatty acids (PUFAs) improve metabolic and anti-inflammatory/antioxidant capacity of the heart, although the mechanisms are unclear and translational evidence is lacking. In this study, patients ingested a moderately high dose of n-3 PUFAs (3.4 g/day eicosapentaenoic (EPA) and doxosahexaenoic acid (DHA) ethyl-esters) for a period of 2-3 weeks before having elective cardiac surgery. Blood was obtained before treatment and at the time of surgery, and myocardial tissue from the right atrium was also dissected during surgery. Blood EPA levels increased and myocardial tissue EPA and DHA levels were significantly higher in n-3 PUFA-treated patients compared with untreated, standard-of-care control patients. Interestingly, n-3 PUFA patients had greater nuclear transactivation of peroxisome proliferator-activated receptor-γ (PPARγ), fatty acid metabolic gene expression, and enhanced mitochondrial respiration supported by palmitoyl-carnitine in the atrial myocardium, despite no difference in mitochondrial content. Myocardial tissue from n-3 PUFA patients also displayed greater expression and activity of key antioxidant/anti-inflammatory enzymes. These findings lead to our hypothesis that PPARγ activation is a mechanism by which fish oil n-3 PUFAs enhance mitochondrial fatty acid oxidation and antioxidant capacity in human atrial myocardium, and that this preoperative therapeutic regimen may be optimal for mitigating oxidative/inflammatory stress associated with cardiac surgery.
authors.affiliation: 1 Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University , Greenville, North Carolina.
authors.forename: Ethan J
authors.initials: EJ
authors.lastname: Anderson
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Thayne
authors.forename: Mitchel
authors.initials: M
authors.lastname: Harris
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Darden
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lark
authors.forename: John Mark
authors.initials: JM
authors.lastname: Williams
authors.forename: W Randolph
authors.initials: WR
authors.lastname: Chitwood
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kypson
authors.forename: Evelio
authors.initials: E
authors.lastname: Rodriguez
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism*; D011446:Prospective Studies; D016037:Single-Blind Method
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma