Increased ω6-Containing Phospholipids and Primary ω6 Oxidation Products in the Brain Tissue of Rats on an ω3-Deficient Diet

Polyunsaturated fatty acyl (PUFA) chains in both the omega 3 and omega 6 series are essential for normal animal brain development, and cannot be interconverted to compensate for a dietary deficiency of one or the other. Paradoxically, a dietary omega 3-PUFA deficiency leads to the accumulation of docosapentaenoate (DPA, 22:5 omega 6), an omega 6-PUFA chain that is normally scarce in the brain. We applied a high-precision LC/MS method to characterize the distribution of DPA chains across phospholipid headgroup classes, the fatty acyl chains with which they were paired, and the extent to which they were oxidatively damaged in the cortical brain of rats on an omega 3-deficient diet. Results indicate that dietary omega 3-PUFA deficiency markedly increased the concentrations of phospholipids with DPA chains across all headgroup subclasses, including plasmalogen species. The concentrations of phospholipids containing docosahexaenoate chains (22:6 omega 3) decreased 20-25%, while the concentrations of phospholipids containing arachidonate chains (20:4 omega 6) did not change significantly. Although DPA chains are more saturated than DHA chains, a larger fraction of DPA chains were monohydroxylated, particularly among diacyl-phosphatidylethanolamines and plasmalogen phosphatidylethanolamines, suggesting that they were disproportionately subjected to oxidative stress. Differences in the pathological significance of omega 3 and omega 6 oxidation products suggest that greater oxidative damage among the omega 6 PUFAs that increase in response to dietary omega 3 deficiency may have pathological significance in Alzheimer's disease.