Molecular mechanism of addiction to animal fat and therapeutic potential of brown rice-specific bioactive substance, gamma-oryzanol for animal fat preference
| Project/Area Number |
17K09839
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
Masuzaki Hiroaki 琉球大学, 医学(系)研究科(研究院), 教授 (00291899)
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| Co-Investigator(Kenkyū-buntansha) |
高山 千利 琉球大学, 医学(系)研究科(研究院), 教授 (60197217)
筒井 正人 琉球大学, 医学(系)研究科(研究院), 教授 (70309962)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肥満症 / 糖尿病 / 食行動変容 / 動物性脂肪依存 / 脳内報酬系 / 玄米 / γ-オリザノール / エピゲノム / γオリザノール / GABA / 食行動 / 内科 / 栄養学 / 脳・神経 / 行動学 |
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| Outline of Final Research Achievements |
We explored the possibility that brown rice-specific bioactive substances, γ-oryzanol would modulate the function of brain reward system in mice. In striatum from mice fed high fat diet, expression of type 2 dopamine receptor (D2R) was decreased via the increase in DNA methylation of its promoter region. Co-administration of γ-oryzanol decreased the expression and activity of DNA methyltransferases (DNMTs), thereby restoring the expression of D2R in striatum. Pharmacological inhibition of DNMTs by 5-aza-2’-deoxycytidine also ameliorated preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in striatum in mice. Our experimental paradigm highlights γ-oryzanol as a promising anti-obesity as well as anti-diabetic substance with a distinct property of novel epigenetic modulator.
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| Academic Significance and Societal Importance of the Research Achievements |
人類が長く食し、長期の安全性が担保されている天然食品に含有される機能成分を糖尿病や肥満症の予防・改善に活用する試み、特に脳機能の改善を目指す枠組みにおいては、長期の安全性と多機能性のバランスの良さを含め、化学合成された医薬では達成できない数々のアドバンテージを有している。本研究により、γ-オリザノールが担う動物脂肪依存改善の中枢制御と包括的代謝改善の新規メカニズムが明らかになったことにより、未だ決定打を欠く肥満症や2型糖尿病などの生活習慣病の改善・予防に貢献できる、まったく新しい医学的アプローチが可能となり、その学術的・臨床的意義は極めて大きい。
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Report
(3 results)
Research Products
(73 results)
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[Journal Article] Appropriate radiation dose for symptomatic relief and local control in patients with adult T cell leukemia/lymphoma.2019
Author(s)
Maemoto H, Ariga T, Nakachi S, Toita T, Hashimoto S, Heianna J, Shiina H, Kusada T, Makino W, Kakinohana Y, Miyagi T, Yamamoto Y, Morishima S, Masuzaki H, Murayama S.
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Journal Title
J Radiat Res
Volume: 60
Issue: 1
Pages: 98-108
DOI
NAID
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Peer Reviewed / Open Access
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[Journal Article] Radiation-induced dermatitis after administration of mogamulizumab for adult T-cell leukaemia/lymphoma: a multi-institutional retrospective study.2019
Author(s)
Maemoto H, Ariga T, Kusada T, Heianna J, Manabe Y, Miyakawa A, Nakachi S, Morishima S, Iraha S, Ganaha F, Masuzaki H, Murayama S
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Journal Title
Jpn J Clin Oncol.
Volume: 49
Issue: 2
Pages: 153-159
DOI
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Peer Reviewed / Open Access
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[Journal Article] Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat.2018
Author(s)
Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y.
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Journal Title
Cell Rep.
Volume: 22
Issue: 3
Pages: 706-721
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Protective Role of Myelocytic Nitric Oxide Synthases Against Hypoxic Pulmonary Hypertension in Mice.2018
Author(s)
Ogoshi T, Tsutsui M, Kido T, Sakanashi M, Naito K, Oda K, Ishimoto H, Yamada S, Wang KY, Toyohira Y, Izumi H, Masuzaki H, Shimokawa H, Yanagihara N, Yatera K, Mukae H.
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Journal Title
Am J Respir Crit Care Med.
Volume: -
Issue: 2
Pages: 232-244
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.2018
Author(s)
Tamaki K, Morishima S, Nomura S, Nishi Y, Nakachi S, Kitamura S, Uchibori S, Tomori S, Hanashiro T, Shimabukuro N, Tedokon I, Morichika K, Taira N, Tomoyose T, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tamaki K, Hayashi M, Uchihara JN, Ohshiro K, Asakura Y, Kuba-Miyara M, Karube K, Fukushima T, Masuzaki H.
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Journal Title
Cancer Sci.
Volume: 109
Issue: 7
Pages: 2286-2293
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.2017
Author(s)
Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M.
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Journal Title
Diabetologia.
Volume: 60
Issue: 6
Pages: 1138-1152
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice.2016
Author(s)
Kozuka C, Shimizu-Okabe C, Takayama C, Nakano K, Morinaga H, Kinjo A, Fukuda K, Kamei A, Yasuoka A, Kondo T, Abe K, Egashira K, Masuzaki H.
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Journal Title
Drug Deliv.
Volume: 24
Issue: 1
Pages: 558-568
DOI
Related Report
Peer Reviewed / Open Access
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[Book] 臨床消化器内科2019
Author(s)
山崎 聡、尾形 絵美、益崎 裕章
Total Pages
500
Publisher
日本メディカルセンター
Related Report
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[Book] 高尿酸血症と痛風2018
Author(s)
益崎 裕章
Total Pages
87
Publisher
メディカルレビュー社
ISBN
4779221404
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[Book] 肥満研究2018
Author(s)
益崎 裕章
Total Pages
165
Publisher
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[Book] 肥満研究2018
Author(s)
岡本 士毅、與那嶺 正人、益崎 裕章、箕越 靖彦
Total Pages
165
Publisher
日本肥満学会誌
Related Report
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[Book] 肥満研究2018
Author(s)
小塚 智沙代、益崎 裕章
Total Pages
165
Publisher
日本肥満学会誌
Related Report
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