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

Abstract

Polyunsaturated fatty acyl (PUFA) chains in both the ω3 and ω6 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 ω3-PUFA deficiency leads to the accumulation of docosapentaenoate (DPA, 22:5ω6), an ω6-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 ω3-deficient diet. Results indicate that dietary ω3-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 (22:6ω3) decreased 20–25%, while the concentrations of phospholipids containing arachidonate chains (20:4ω6) 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 ω3 and ω6 oxidation products suggest that greater oxidative damage among the ω6 PUFAs that increase in response to dietary ω3 deficiency may have pathological significance in Alzheimer’s disease.

Free Radical Chain Reactions and Polyunsaturated Fatty Acids in Brain Lipids

“…These yields are comparable to the concentrations previously reported. 18 , 20 Figure 2 shows the effect of adding synthetic DMPC, SAPC and SDPC on the oxidative degradation of endogenous SAPC and SDPC. It should be noted that the loss of SAPC when synthetic SDPC was added represents the loss of endogenous SAPC.…”

Do Eicosapentaenoic Acid and Docosahexaenoic Acid Have the Potential to Compete against Each Other?

“…Several labs report that EPA and DHA are differentially incorporated into distinct membrane phospholipids [25]. The uptake of EPA and DHA is selective and varies between PC, PE, phosphatidylserines (PS), and phosphatidylinositols (PI) [26,27]. EPA has been reported to be preferentially incorporated into PC followed by PE as compared to DHA, which has been found to be highest in PE followed by PC in erythrocyte membranes of healthy humans [28].…”

Spatial Distribution of Transcytosis Relevant Phospholipids in Response to Omega-3 Dietary Deprivation

“…The phospholipid profile changes that we observed under omega-3 dietary deficiency agreed with previous omega-3 deficient diet studies, and they are also similar to phospholipid perturbations characteristic of neurodegenerative diseases. An increase in phospholipid species containing fewer degrees of unsaturation in response to omega-3 deprivation has previously been identified in experiments that used LC MS to investigate the brain lipidomic changes in animals fed an omega-3 deficient diet. − PUFAs with increased saturation in the brain are considered to be more liable to oxidation and are classified as pro-inflammatory molecules . As such, pro-inflammatory PUFAs are thought to contribute to the development of neurodegenerative diseases, such as Alzheimer’s Disease. − Neurodegenerative diseases have also been shown to have increased levels of ceramides, which was one of the two changes in phospholipid profiles that we observed in our data.…”

“…Considering the high abundance of omega-3 PUFAs in the brain and their link to neurodegenerative diseases, the effects of n-3 deficient diets on the mammalian brain have been investigated in a number of studies. Omega-3 deficient conditions have been reported to impact functional and behavioral aspects in mammals. , One of the key biochemical findings from animals exposed to n-3 deficient diets is an increase in the omega-6 (n-6) fatty acid docosapentaenoic acid (DPA) (22:5 n-6), and research has suggested DPA (22:5 n-6) could be responsible for some of the functional and behavioral effects observed in animals fed n-3 deficient diets. − Furthermore, fatty acids and their metabolites have been shown to regulate gene expression, including in the brains of animals exposed to n-3 deficient diets, in a manner that is independent of their effects on membrane composition …”