title: Dietary omega-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition.
abstract: Consumption of omega-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA + DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA + DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospholipid composition, respiration, and sensitivity to mitochondrial permeability transition pore (MPTP) opening in normal and infarcted myocardium. Rats were subjected to sham surgery or myocardial infarction by coronary artery ligation (n=10-14), and fed a standard diet, or supplemented with EPA + DHA (2.3% of energy intake) for 12 weeks. EPA + DHA altered fatty acid composition of total mitochondrial phospholipids and cardiolipin by reducing arachidonic acid content and increasing DHA incorporation. EPA + DHA significantly increased calcium uptake capacity in both subsarcolemmal and intrafibrillar mitochondria from sham rats. This treatment effect persisted with the addition of cyclosporin A, and was not accompanied by changes in mitochondrial respiration or coupling, or cyclophilin D protein expression. Myocardial infarction resulted in heart failure as evidenced by LV dilation and contractile dysfunction. Infarcted LV myocardium had decreased mitochondrial protein yield and activity of mitochondrial marker enzymes, however respiratory function of isolated mitochondria was normal. EPA + DHA had no effect on LV function, mitochondrial respiration, or MPTP opening in rats with heart failure. In conclusion, dietary supplementation with EPA + DHA altered mitochondrial membrane phospholipid fatty acid composition in normal and infarcted hearts, but delayed MPTP opening only in normal hearts.
authors.affiliation: Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: O'Shea
authors.forename: Ramzi J
authors.initials: RJ
authors.lastname: Khairallah
authors.forename: Genevieve C
authors.initials: GC
authors.lastname: Sparagna
authors.forename: Wenhong
authors.initials: W
authors.lastname: Xu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hecker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robillard-Frayne
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
authors.forename: Tibor
authors.initials: T
authors.lastname: Kristian
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.forename: Gary
authors.initials: G
authors.lastname: Fiskum
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002308:Cardiolipins / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004452:Echocardiography; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002308:Cardiolipins; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010743:Phospholipids; D013481:Superoxides; D016572:Cyclosporine; D002118:Calcium
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