Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2020-11-11 |
タイトル |
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タイトル |
Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice |
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言語 |
ja |
作成者 |
Kozuka, Chisayo
Kaname, Tadashi
Shimizu-Okabe, Chigusa
Takayama, Chitoshi
Tsutsui, Masato
Matsushita, Masayuki
Abe, Keiko
Masuzaki, Hiroaki
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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言語 |
en |
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権利情報 |
Creative Commons Attribution 4.0 |
権利情報 |
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言語 |
en |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
https://creativecommons.org/licenses/by/4.0/ |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
DNA methylation |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Dopamine |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Epigenetics |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Feeding behaviour |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Nutrition |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Obesity |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Reward |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Striatum |
主題 |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Type 2 diabetes |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Aims/hypothesis Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent gamma-oryzanol attenuated the preference for an HFD via hypothalamic control. We therefore explored the possibility that gamma-oryzanol would modulate functioning of the brain reward system in mice.\nMethods Male C57BL/6J mice fed an HFD were orally treated with gamma-oryzanol, and striatal levels of molecules involved in D2R signalling were evaluated. The impact of gamma-oryzanol on DNA methylation of the D2R promoter and subsequent changes in preferences for dietary fat was examined. In addition, the effects of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methyltransferases (DNMTs), on food preference, D2R signalling and the levels of DNMTs in the striatum were investigated. The inhibitory effects of gamma-oryzanol on the activity of DNMTs were enzymatically evaluated in vitro.\nResults In striatum from mice fed an HFD, the production of D2Rs was decreased via an increase in DNA methylation of the promoter region of the D2R. Oral administration of gamma-oryzanol decreased the expression and activity of DNMTs, thereby restoring the level of D2Rs in the striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated the preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that gamma-oryzanol inhibited the activity of DNMTs.\nConclusions/interpretation We demonstrated that gamma-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in the striatum of mice. Our experimental paradigm highlights gamma-oryzanol as a promising antiobesity substance with the distinct property of being a novel epigenetic modulator. |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
論文 |
出版者 |
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言語 |
en |
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出版者 |
Springer Nature |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ |
journal article |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
識別子 |
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識別子 |
http://hdl.handle.net/20.500.12000/47185 |
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識別子タイプ |
HDL |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1007/s00125-017-4305-4 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1007/s00125-017-4305-4 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0012-186X |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1432-0428 |
収録物名 |
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言語 |
en |
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収録物名 |
Diabetologia |
書誌情報 |
巻 60,
p. 1502-1511,
発行日 2017-05-20
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