The enhancement of hippocampal neurogenesis by ω-3 polyunsaturated fatty acids is an important tool for treating neurodegenerative diseases, such as Alzheimer's disease, and to enhance learning and memory. The exact mechanisms of action, however, remain poorly understood. We have previously reported that docosahexaenoic acid (DHA) decreases mRNA levels of Hes1, an inhibitor of neuronal differentiation, and increases NeuroD and Map2 mRNA, as well as the number of TuJ1-positive (a neuronal marker) cells, indicating that DHA induces neuronal differentiation. Eicosapentaenoic acid (EPA) increases mRNA levels of Hes1, Hes6, an inhibitor of Hes1, NeuroD, and Map2, as well as TuJ1-positive cells, indicating that EPA also induces neuronal differentiation. However, treatment with arachidonic acid (ARA) decreases Hes1 mRNA, but does not affect mRNA expression of NeuroD and Map2. Furthermore, ARA does not affect the number of TuJ1-positive cells. DHA and EPA, but not ARA, increase mRNA levels of p21 and p27, cyclin-dependent kinase inhibitors, indicating that DHA and EPA induce cell cycle arrest. These results suggest that EPA could be involved in neuronal differentiation by mechanisms that are different to DHA. We also have reported that N-docosahexaenoylethanolamine (synaptamide), an endogenous DHA metabolite with an endocannabinoid-like structure, promotes neuronal differentiation of neural stem cells at a lower dose than DHA and that its action takes place via protein kinase A/cAMP response element binding protein activation. These results suggest that the transduction of intracellular signaling is involved in ω-3 polyunsaturated fatty acid-induced neurogenesis. However, the receptors or binding proteins are involved this mechanism, as well as other metabolites, remain to be shown.

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Glycidol fatty acid esters (GE) have been found as impurities in a refained edible oil in Germen in 2009. German officials published the first risk assessment because GE has concern of possible exposure to glycidol which is classified as a genotoxic carcinogen. Food safety commission of Japan began risk evaluation of diacylglycerol oil (brand name: Econa cooking oil) which contained much higher content of GE than in ordinary edible oils in 2009. The commission has published the risk assessment report in March 2015. The report has showed 1) safety assessment of food contained diaclyglycerol oil and 2) about safety of GE as impurities in fats and oils. GE was a novel substance that found in food, therefore, development of quantitative qualification method was priority challenge globally. Four quantitative qualification methods used to detect GE in edible oil as well as fat processed food have been registered as AOCS official method as of 2015 end. Recently, Japanese officials has revealed research results of GE content in edible oils and fat processed foods in "risk profile sheet of GE" that was published in March 2015. The GE content in products in Japanese market were lower level than that of products reported in oversea. Current information of GE regarding the risk assessment published by Japanese officials, international development of analytical method and research result of GE content in foods have been updated in this manuscript.

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Accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine, in blood plasma has been observed under vascular pathological conditions, such as atherosclerosis. PCOOH isomer analysis may lead to the elucidation of the mechanism of in vivo peroxidative reactions. In this study, we investigated the use of LC-MS/MS to develop a method for accurate quantification of PCOOH (1-palmitoyl-2-hydroperoxy-octadecadienoyl-sn-glycero-3-phosphocholine, 16:0/　HpODE PC), focusing specifically on isomers such as 16:0/9(13)-HpODE PC that might be predominantly present in human plasma. Collision-induced dissociation of sodiated PCOOH isomers ([M+Na]+, m/z 812) provided not only a known fragment ion (m/z 147), but also characteristic product ions (m/z 388 for 16:0/9-HpODE PC and m/z 541 for 16:0/13-HpODE PC). MRM (812/147) enabled determination of plasma PCOOH (16:0/HpODE PC), regardless of the position of the hydroperoxide group in the fatty acid. MRM (812/541 and 812/388) allowed specific measurement of 16:0/13-HpODE PC and 16:0/9-HpODE PC. By using this method, we could determine plasma PCOOH concentrations in healthy subjects and in patients with angiographically significant stenosis. In both plasma, the concentration of 16:0/HpODE PC was close to the sum of the concentrations of 16:0/13-HpODE PC and 16:0/9-HpODE PC. These findings suggest that radical- and/or enzymatic-oxidation, rather than singlet oxygen-oxidation, are recognized to cause peroxidation of fatty acid residues of lipoprotein membrane PC. The newly developed LC-MS/MS method appears to be a powerful tool for developing a better understanding of in vivo lipid peroxidation and its involvement in human diseases.

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Bile acids exert anti-obesity and anti-hyperglycemic effects through a G protein-coupled receptor TGR5. In L cells located in the lower small intestine TGR5 activation stimulates secretion of a peptide hormone GLP-1 that enhances insulin sensitivity. In brown adipose tissues and skeletal muscles its activation results in an increase in energy expenditure, leading to anti-obesity effects. Based on these findings, we searched for food factors that mimic bile acid functions, and identified a citrus limonoid nomilin as a powerful agonist for TGR5. Simulation analyses for TGR5-nomilin association and mutation analyses of human TGR5 revealed that TGR5 is capable of biding nomilin through three amino acid residues located in a transmembrane and extracellular domain. Further analyses using transgenic mice overexpressing human TGR5 in skeletal muscles showed that TGR5 activation results in an increase in muscle mass. Taken together, we believe that TGR5 is one of ideal targets for functional food factors to extend healthy life expectancy.

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In April 2015, the Consumer Affairs Agency, Government of Japan introduced a new system on foods, called Foods with Function Claims. The food products are to be labelled clearly with nutritional function based on certain scientific evidence. The food business operators are required to submit with collect information on the food's effectiveness and safety. The foods submitted are disclosed on the website of the Consumer Affairs Agency. The new system on foods may be valuable for consumers when they select a proper food for their health. In this paper, we described a subject to be solved in this system on foods because of the scientific terms of Foods for Health Claims are not clear. In general, foods contain essential substances for our health and the nutrients of the Foods with Function Claims are crucial in the metabolism process. However, the function of the nutrients may have a limited effect on human health when compared to that of medicine. It is very important for customers to know that the Foods with Function Claim are not medicine. In conclusion, the technical terms of the new system on foods, Foods with Function Claims, should be explained clearly for customers by the academic association of nutrition.

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A large number of reports about physiological functions of α-linolenic acid (LNA) have been presented. And it is also well known that LNA is highly contained in perilla seed oil. In the second half in 1980's, we (Ohta Oilmill Co.,Ltd) succeeded in industrializing of edible perrila seed oil for the first time in Japan. At the industrialization of edible perilla seed oil, we had to resolve the important technical problem about the stability of LNA in production process and during product storage. LNA is polyunsaturated fatty acid, so we had to prevent the degradation and the oxidation of LNA. After a lot of serious investigations about that, we could develop the optimum condition of refinement process and the way to prevent the autoxidation during storage. Perilla is firm products, so it's possible for us to produce perilla seed oil stably and sustainably. Now we can present several kinds of perilla seed oil products, moreover we hope we will contribute to the health and welfare of many people.

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kn-abstract=We investigated that the effects of the 'live high-train low' methods using normobaric hypoxia with or without fish oil supplement on the endurance performances. Twelve male ekiden-runners in the university were divided into two groups; one group (non-fish oil group, n=6) spent in normobaric hypoxic room 8 h per day (equal to ~2500 m) for 3 weeks, the other group spent in the same condition for the same period with supplementation of fish oil for 7 weeks (fish oil group, n=6). Administration of the fish oil supplement was started 4 weeks prior to using hypoxic environment. The blood examinations were performed before and after the total experimental protocol, and the running tests using treadmill machine were conducted before and after using hypoxic environment. The concentrations of eicosapentaenoic acid (EPA) in the blood in the fish oil group significantly increased from 77.2±16.8 to 126.5±11.2 μg/mL. Hemoglobin concentrations (Hb) and hematocrit levels (Ht) were significantly increased after hypoxic training in the non-fish oil group. However, in the fish oil group, both Hb and Ht were not significantly changed after using hypoxic environment. The lactic acid levels in the running test at 18.8-19.4 km/h in the non-fish oil group and at 20.6 km/h in the fish oil group were significantly decreased. We also estimated the speed of onset of blood lactate accumulation (SP-OBLA). Although SP-OBLAs in both groups were slightly increased after using hypoxic environment, there was no significant difference between the two groups. It was concluded that the 3 weeks of 'live high - train low' methods using normobaric hypoxia with fish oil supplement may improve the endurance performances without increase of Hb and Ht. It is speculated that fish oil supplementation reduces the cardiovascular loading via increase of Ht during hypoxic training without blunting the improvement of endurance performance.

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Recent studies have shown beneficial effects of dietary sphingolipids on our health and beauty, such as prevention of aberrant crypt foci formation and enhancing skin beauty. It is important to know amount and type of dietary sphingolipid for understanding mechanisms underlying these effects. In this study, we quantified glycosylinositol phosphoceramide (GIPC), one of major plant sphingolipids, in foodstuffs. We found that GIPC was contained in all vegetables examined (13 kinds of vegetables) at a rage from 3 to 20 mg/100 g (wet weight), but not in meats and eggs. Daily intake of GIPC was estimated to be approximately 28 mg/day, which is similar level to that of glycosylceramides. We also determined phytoceramide-1-phosphate (PC1P), a hydrolysate of GIPC, in vegetables. Relatively high amount of PC1P was detected in lipids from raw cabbage leaves and raw radish roots (5.2 and 2.3 mg/100 g, respectively). PC1P was found to be converted to phytoceramide by intestinal alkali phosphatase. From these results, it is considered that a portion of GIPC in cruciferous vegetables is absorbed via phytoceramide after conversion of GIPC to PC1P by endogenous GIPC-specific phospholipase D.

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