Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids

Abstract

Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival

“…The phospholipid fatty acid composition of IFM in the prevention protocol was measured using gas chromatography-mass spectrometry in homogenates made from frozen aliquots according to a modification of the transesterification method as previously described (12,28).…”

Omega-3 fatty acid supplementation and cardiovascular disease

“…As noted above, the capacity of the dietary 3 PUFA supplementation to increase cardiac muscle DHA may be important in the prevention of ventricular fi brillation and SCD ( 179,230,234 ). Fatty fi sh, fi sh oil containing EPA + DHA, or the DHA-only supplements (e.g., DHASCO and MATK-90) represent the only routes to signifi cantly increase blood and tissue DHA content.…”

Effect of omega-3 fatty acid oxidation products on the cellular and mitochondrial toxicity of BDE 47

“…Interestingly, the onset of MPTP opening can be delayed by dietary supplementation with DHA [59, 60], supporting a role of DHA in stabilizing ΔΨ m . Dietary supplementation with omega-3s, particularly DHA, is reported to have significant beneficial effects on mitochondrial membranes and function [61]. Our results suggest the oxidation products of omega-3s may mediate some of the beneficial effects on mitochondrial membranes by significantly limiting loss of ΔΨ m from BDE 47 exposure.…”