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j.isci.2023.106161.pdf | 8.32 MB | Adobe PDF | 見る/開く |
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DCフィールド | 値 | 言語 |
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dc.contributor.author | Kwon, Jungin | en |
dc.contributor.author | Yeh, Yu-Sheng | en |
dc.contributor.author | Kawarasaki, Satoko | en |
dc.contributor.author | Minamino, Hiroto | en |
dc.contributor.author | Fujita, Yoshihito | en |
dc.contributor.author | Okamatsu-Ogura, Yuko | en |
dc.contributor.author | Takahashi, Haruya | en |
dc.contributor.author | Nomura, Wataru | en |
dc.contributor.author | Matsumura, Shigenobu | en |
dc.contributor.author | Yu, Rina | en |
dc.contributor.author | Kimura, Kazuhiro | en |
dc.contributor.author | Saito, Masayuki | en |
dc.contributor.author | Inagaki, Nobuya | en |
dc.contributor.author | Inoue, Kazuo | en |
dc.contributor.author | Kawada, Teruo | en |
dc.contributor.author | Goto, Tsuyoshi | en |
dc.contributor.alternative | 權, 庭仁 | ja |
dc.contributor.alternative | 葉, 語勝 | ja |
dc.contributor.alternative | 川原﨑, 聡子 | ja |
dc.contributor.alternative | 南野, 寛人 | ja |
dc.contributor.alternative | 藤田, 義人 | ja |
dc.contributor.alternative | 高橋, 春弥 | ja |
dc.contributor.alternative | 野村, 亘 | ja |
dc.contributor.alternative | 稲垣, 暢也 | ja |
dc.contributor.alternative | 井上, 和生 | ja |
dc.contributor.alternative | 河田, 照雄 | ja |
dc.contributor.alternative | 後藤, 剛 | ja |
dc.date.accessioned | 2024-02-22T01:49:27Z | - |
dc.date.available | 2024-02-22T01:49:27Z | - |
dc.date.issued | 2023-03-17 | - |
dc.identifier.uri | http://hdl.handle.net/2433/287063 | - |
dc.description.abstract | The high thermogenic activity of brown adipose tissue (BAT) has received considerable attention. Here, we demonstrated the role of the mevalonate (MVA) biosynthesis pathway in the regulation of brown adipocyte development and survival. The inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme in the MVA pathway and the molecular target of statins, suppressed brown adipocyte differentiation by suppressing protein geranylgeranylation-mediated mitotic clonal expansion. The development of BAT in neonatal mice exposed to statins during the fetal period was severely impaired. Moreover, statin-induced geranylgeranyl pyrophosphate (GGPP) deficiency led to the apoptosis of mature brown adipocytes. Brown adipocyte-specific Hmgcr knockout induced BAT atrophy and disrupted thermogenesis. Importantly, both genetic and pharmacological inhibition of HMGCR in adult mice induced morphological changes in BAT accompanied by an increase in apoptosis, and statin-treated diabetic mice showed worsened hyperglycemia. These findings revealed that MVA pathway-generated GGPP is indispensable for BAT development and survival. | en |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | en |
dc.rights | © 2023 The Author(s). | en |
dc.rights | This is an open access article under the CC BY-NC-ND license. | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | - |
dc.subject | Biochemistry | en |
dc.subject | Biological sciences | en |
dc.subject | Molecular Genetics | en |
dc.title | Mevalonate biosynthesis pathway regulates the development and survival of brown adipocytes | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | iScience | en |
dc.identifier.volume | 26 | - |
dc.identifier.issue | 3 | - |
dc.relation.doi | 10.1016/j.isci.2023.106161 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | 106161 | - |
dc.identifier.pmid | 36895651 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 19H02910 | - |
datacite.awardNumber | 20K21755 | - |
datacite.awardNumber | 22H02287 | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19H02910/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20K21755/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22H02287/ | - |
dc.identifier.eissn | 2589-0042 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | 脂肪組織機能調節におけるコレステロール代謝系の生理的役割の解明 | ja |
jpcoar.awardTitle | 褐色脂肪組織による骨格筋機能制御機構の解明 新規褐色脂肪欠失マウスを用いた検討 | ja |
jpcoar.awardTitle | 肥満状態の脂肪組織機能破綻におけるコレステロール生合成経路の意義の解明 | ja |
出現コレクション: | 学術雑誌掲載論文等 |
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