− この都医学研セミナーは終了しました。 −
|演者||Andrew J Sinclair（University of Australia Professor of Nutrition Science）|
|世話人||楯林 義孝 副参事研究員（統合失調症・うつ病プロジェクト）|
The realisation that brain grey matter from many different mammals was rich in n-3 long chain polyunsaturated fatty acids (n-3 LCP), especially DHA, was a stimulus for much research on the biological role(s) of n-3. Since then many studies have been conducted to investigate the beneficial effects of n-3 LCP in neural function, reducing risk the of cardiovascular events, diabetes mellitus, inhibiting growth of tumour cells, modulating gene expression, anti-inflammatory activity and lipid lowering potential. Most of these studies have been conducted using fish oils which typically contain all the three n-3 LCP, namely eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid, (DHA). Many studies have addressed the unique actions of EPA and DHA individually, because these two fatty acids have been available in purified form. What has emerged from this research is that there are both unique as well as overlapping actions. For example DHA has unique actions in promoting normal functioning of brain, while both EPA and DHA have overlapping actions in lowering blood lipid levels. Because pure DPA has not been readily available in quantity or at an affordable price, the role(s) of DPA have not been systematically examined.
This talk will summarise the current knowledge available on metabolism and the biological effects of n-3 docosapentaenoic acid (DPA, 22:5n-3) and discuss the results of pilot study in human subjects. DPA is an elongated metabolite of EPA and is an intermediary product between EPA and DHA. In vitro DPA is retro-converted to EPA, however it does appear to be readily metabolised to DHA. In vivo studies have shown limited conversion of DPA to DHA, mainly in the liver tissue, but in addition apparent retro-conversion to EPA is evident in a number of tissues. DPA can be metabolised by lipoxygenase, in platelets, to form 11-hydroxy-7,9,13,16,19- and 14-hydroxy-7,10,12,16,19-DPA. It has also been reported that DPA is effective (more so than EPA and DHA) in inhibition of platelet aggregation in platelets obtained from rabbit blood. In addition, there is evidence that DPA possesses 10-fold greater endothelial cell migration ability than EPA, which is important in wound healing processes. A more recent in vivo study has reported that DPA reduces the fatty acid synthase and malonyl activity levels in DPA-supplemented mice and these effects were stronger than the EPA-supplemented mice. However, more research remains to be done to further investigate the biological effects of this n-3 LCP.
Using a target lipidomics approach, the human plasma profile of lipid mediator species derived from cyclooxygenase (COX-1 and 2), lipooxygenase (5-, 12-, 15-LOX), and epoxygenase (CYP) pathways was determined after female subjects (n=8) ingested 8 grams daily of pure EPA, DPA, or placebo control (olive oil; OO) over a 7-day period. In total 126 lipid mediator species resolved by LC-MS fasting plasma drawn at the end of dietary fatty acid supplementation. 29 lipid mediator species were influenced by OO supplementation, whilst EPA and DPA supplementation uniquely regulated a further 37 and 27 lipid mediators, respectively. DPA supplementation resulted in marked (? 20-fold) increase in plasma concentration of the putative bioactive DHA metabolites 7,17-DiHDoPE and 19,20-DiHDoPE. Additionally, the DHA metabolites resolvin D1 (RvD1) and 7(S)-Maresin1 were increased (30-60%) by DPA. EPA supplementation, circulating EPA metabolites, most notably LOX-derived hydroxyl-eicosapentaenoic acids (HEPEs), 8-HEPE and 18-HEPE increased >10 fold. Additionally, EPA derived prostaglandins (PGE3), leukotrienes (LTB5), and remaining HEPEs (5-, 9-, 11-, 12-, 15-HEPE) were elevated (~2 fold). All EPA metabolites remained unaltered following DPA supplementation. Furthermore, there were differences between DPA and EPA in postprandial chylomicromaemia and incorporation of DPA and EPA into plasma and red blood cell lipid species. Lipidomic analysis was able to resolve the unique metabolites derived from differing dietary omega-3 species. Short term dietary supplementation with DPA or EPA has distinct and divergent modulatory effects on human plasma lipid mediator profile.