Abstract 3067: Fish Oil Supplementation Alters Mitochondrial Membrane Phospholipid Composition and Prevents Calcium-induced Mitochondrial Permeability Transition in the Rat Heart
Mitochondrial dysfunction contributes to cardiac pathology in heart disease, and opening of the mitochondrial permeability transition pore (MPTP) is associated with cardiomyocyte death, tissue injury, and poor function. Dietary supplementation with omega-3 fatty acids from fish oil (FO) alters cardiac phospholipid (PL) composition and is cardioprotective. We hypothesize that FO supplementation favorably alters mitochondrial PL composition and prevents MPTP. Male rats were fed either standard chow (STD) or a FO supplemented diet (2.3% of energy intake as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), comparable to ~5g/day in humans). Cardiac subsarcolemmal (SSM) and intrafibrillar (IFM) mitochondria were isolated after 12 weeks on diet. FO increased incorporation of DHA into mitochondrial PL 2.5-fold compared to STD diet and decreased arachidonic acid, a precursor for proinflammatory mediators and potential trigger for MPTP opening. Diet did not affect State 3 or 4 respiration, RCR or P:O ratio with a wide range of substrates in SSM or IFM. However, FO supplementation dramatically delayed calcium-induced MPTP opening in both SSM and IFM compared to STD chow (P<0.001), as measured by extramitochondrial calcium increase. There were no differences in cyclophilin D or VDAC protein expression. Cyclosporin A delayed MPTP to a similar extent in both STD and FO groups.
CONCLUSION: FO supplementation favorably altered mitochondrial PL composition and significantly delayed MPTP opening in cardiac mitochondria. These effects may contribute to the protection against ischemic injury and heart failure observed with FO supplementation in recent clinical studies.