著者
Hisanori Tokuda Toshiaki Sueyasu Masanori Kontani Hiroshi Kawashima Hiroshi Shibata Yoshihiko Koga
出版者
Japan Oil Chemists' Society
雑誌
Journal of Oleo Science (ISSN:13458957)
巻号頁・発行日
vol.64, no.6, pp.633-644, 2015 (Released:2015-06-01)
参考文献数
51
被引用文献数
8 23

Several studies have reported that the supplementation of long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) improve cognitive function in the elderly. However, the doses used in these studies were higher than general dietary LCPUFA intake levels. This randomized, double-blind, placebo-controlled trial evaluated the effects of low doses of LCPUFA supplementation corresponding to general dietary intake on cognitive function in non-demented elderly Japanese participants. Japanese men aged 55-64 years were enrolled and randomly allocated to the placebo or LCPUFA group. Participants received 4 weeks of supplementation with LCPUFA-containing oil (DHA, 300 mg/day; EPA, 100 mg/day; and ARA, 120 mg/day) or purified olive oil as placebo. Event-related potential P300, reflecting cognitive processes, was measured before and after supplementation. A total of 113 participants completed the supplementation period, and the per-protocol analysis included 69 participants. Changes in P300 latency were significantly different between the placebo group (+13.6 msec) and the LCPUFA group (-1.8 msec) after supplementation. Significant increases in DHA (+0.9%) and ARA (+0.6%) contents in plasma phospholipids were observed in the LCPUFA group; no changes were observed in the placebo group. Dietary DHA, EPA, and ARA intake were in the normal range for Japan participants and remained unchanged during the study. These results suggest that low doses of LCPUFA supplementation have the potential to improve cognitive function in elderly Japanese men.
著者
Tomohiro Suzuki Mayuko Hayashi Tetsuro Komatsu Akiko Tanioka Masahiro Nagasawa Kyoko Tanimura-Inagaki Mohammad Sharifur Rahman Shinnosuke Masuda Kosuke Yusa Juro Sakai Hiroshi Shibata Takeshi Inagaki
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ21-0255, (Released:2021-07-15)
被引用文献数
3

α-Ketoglutarate (α-KG) also known as 2-oxoglutarate (2-OG) is an intermediate metabolite in the tricarboxylic acid (TCA) cycle and is also produced by the deamination of glutamate. It is an indispensable cofactor for a series of 2-oxoglutarate-dependent oxygenases including epigenetic modifiers such as ten-eleven translocation DNA demethylases (TETs) and JmjC domain-containing histone demethylases (JMJDs). Since these epigenetic enzymes target genomic DNA and histone in the nucleus, the nuclear concentration of α-KG would affect the levels of transcription by modulating the activity of the epigenetic enzymes. Thus, it is of great interest to measure the nuclear concentration of α-KG to elucidate the regulatory mechanism of these enzymes. Here, we report a novel fluorescence resonance energy transfer (FRET)-based biosensor with multiple nuclear localization signals (NLSs) to measure the nuclear concentration of α-KG. The probe contains the α-KG-binding GAF domain of NifA protein from Azotobacter vinelandii fused with EYFP and ECFP. Treatment of 3T3-L1 preadipocytes expressing this probe with either dimethyl-2-oxoglutarate (dimethyl-2-OG), a cell-permeable 2-OG derivative, or citrate elicited time- and dose-dependent changes in the FRET ratio, proving that this probe functions as an α-KG sensor. Measurement of the nuclear α-KG levels in the 3T3-L1 cells stably expressing the probe during adipocyte differentiation revealed that the nuclear concentration of α-KG increased in the early stage of differentiation and remained high thereafter. Thus, this nuclear-localized α-KG probe is a powerful tool for real-time monitoring of α-KG concentrations with subcellular resolution in living cells and is useful for elucidating the regulatory mechanisms of epigenetic enzymes.
著者
Nobuyuki Sakayori Hisanori Tokuda Kaichi Yoshizaki Hiroshi Kawashima Sheila M. Innis Hiroshi Shibata Noriko Osumi
出版者
Tohoku University Medical Press
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.240, no.1, pp.31-37, 2016 (Released:2016-08-24)
参考文献数
29
被引用文献数
8 19

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and α-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LAex/ALAdef) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LAex/ALAdef diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LAex/ALAdef diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring’s sex. Since the n-6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring’s anxiety-related behavior with a sex-dependent manner.
著者
Hisanori Tokuda Toshiaki Sueyasu Hiroshi Kawashima Hiroshi Shibata Yoshihiko Koga
出版者
公益社団法人 日本油化学会
雑誌
Journal of Oleo Science (ISSN:13458957)
巻号頁・発行日
vol.66, no.7, pp.713-721, 2017 (Released:2017-07-01)
参考文献数
35
被引用文献数
5

Although several studies have reported the effects of long-chain polyunsaturated fatty acid (LCPUFA) supplementation on the mood in healthy adults, the effects of LCPUFA on elderly individuals remain unclear. Thus, we hypothesized that LCPUFA supplementation improves mood in the elderly. To address this hypothesis, 115 elderly Japanese men aged 55-64 years were assigned and randomly allocated to the LCPUFA or placebo group. Participants received 4 weeks of supplementation with LCPUFA-containing oil (docosahexaenoic acid (DHA) 300 mg/day, eicosapentaenoic acid (EPA) 100 mg/day, arachidonic acid (ARA) 120 mg/day) or a placebo oil. Mood was assessed using the Profile of Mood States (POMS) before and after supplementation as the secondary outcome in a previously performed randomized controlled trial on cognitive function. A total of 113 participants completed the supplementation period. One hundred participants (LCPUFA, n = 51; placebo, n = 49) who were eligible for evaluation of mood were analyzed. Increases in vigor scores on POMS, reflecting a positive mood, were significantly larger in the LCPUFA group than in the placebo group (LCPUFA, +1.8; placebo, −0.5). No significant differences were observed in changes in other negative mood scores between groups. DHA and ARA content in plasma phospholipids were increased by 0.8% and 0.7%, respectively, in the LCPUFA group, and were significantly larger than those in the placebo group. Dietary DHA, EPA, and ARA intake was unchanged during the study. These results suggest that LCPUFA supplementation may improve vigor (positive mood) in elderly Japanese men.
著者
Hisanori Tokuda Toshiaki Sueyasu Hiroshi Kawashima Hiroshi Shibata Yoshihiko Koga
出版者
公益社団法人 日本油化学会
雑誌
Journal of Oleo Science (ISSN:13458957)
巻号頁・発行日
pp.ess17035, (Released:2017-06-13)
被引用文献数
5

Although several studies have reported the effects of long-chain polyunsaturated fatty acid (LCPUFA) supplementation on the mood in healthy adults, the effects of LCPUFA on elderly individuals remain unclear. Thus, we hypothesized that LCPUFA supplementation improves mood in the elderly. To address this hypothesis, 115 elderly Japanese men aged 55-64 years were assigned and randomly allocated to the LCPUFA or placebo group. Participants received 4 weeks of supplementation with LCPUFAcontaining oil (docosahexaenoic acid (DHA) 300 mg/day, eicosapentaenoic acid (EPA) 100 mg/day, arachidonic acid (ARA) 120 mg/day) or a placebo oil. Mood was assessed using the Profile of Mood States (POMS) before and after supplementation as the secondary outcome in a previously performed randomized controlled trial on cognitive function. A total of 113 participants completed the supplementation period. One hundred participants (LCPUFA, n = 51; placebo, n = 49) who were eligible for evaluation of mood were analyzed. Increases in vigor scores on POMS, reflecting a positive mood, were significantly larger in the LCPUFA group than in the placebo group (LCPUFA, +1.8; placebo, −0.5). No significant differences were observed in changes in other negative mood scores between groups. DHA and ARA content in plasma phospholipids were increased by 0.8% and 0.7%, respectively, in the LCPUFA group, and were significantly larger than those in the placebo group. Dietary DHA, EPA, and ARA intake was unchanged during the study. These results suggest that LCPUFA supplementation may improve vigor (positive mood) in elderly Japanese men.
著者
Yuji NONAKA Takayuki IZUMO Toshihiro MAEKAWA Hiroshi SHIBATA
出版者
BMFH出版会
雑誌
Bioscience of Microbiota, Food and Health (ISSN:21863342)
巻号頁・発行日
vol.36, no.3, pp.121-128, 2017 (Released:2017-07-13)
参考文献数
48
被引用文献数
1

We investigated if the orally administered Lactobacillus pentosus strain S-PT84 (S-PT84) might show anti-stress activity and ameliorate stress-induced immune suppression in mice. Stress of mice induced an increase in serum corticosterone and a decrease in splenic natural killer activity and in the number of splenocytes versus control mice. However, these changes were not observed in stressed mice that had been administered S-PT84. Furthermore, interleukin (IL)-12 and IL-10 production, which was downregulated in lipopolysaccharide-activated macrophages from stressed mice, was maintained at control levels in the macrophages of stressed mice that had been fed S-PT84. Interferon-γ production, which was downregulated in concanavalin A-activated splenocytes from stressed mice, tended to be maintained at control levels in stressed mice that had been fed S-PT84, although IL-4 production by these cells was not influenced by S-PT84 administration. Additionally, reduced glutathione (GSH) levels were decreased in serum and peritoneal macrophages from stressed mice versus controls, but these GSH levels were significantly higher in stressed animals that had been administered S-PT84 compared with those that had not. These results suggest that S-PT84 exerts anti-stress activity through immune modulation and/or antioxidative activity.