ID | 118313 |
タイトル別表記 | キサンチンオキシダーゼ阻害薬febuxostatはNrf2を活性化し脂肪細胞分化を抑制する
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著者 |
比嘉, 佳基
徳島大学大学院口腔科学研究科(口腔科学専攻)
中上, 絵美子
Tokushima University
Tanaka, Mariko
Tokushima University
Kim, Sooha
Tokushima University
Nakagawa, Motosumi
Tokushima University
谷本, 幸多朗
Tokushima University
Oda, Asuka
Tokushima University
Maruhashi, Tomoko
Tokushima University
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キーワード | obesity
adipocytic differentiation
reactive oxygen species (ROS)
xanthine oxidoreductase (XOR)
febuxostat
Nrf2
Keap1
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資料タイプ |
学位論文
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抄録 | Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating.
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掲載誌名 |
Antioxidants
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ISSN | 20763921
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出版者 | MDPI
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巻 | 12
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号 | 1
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開始ページ | 133
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発行日 | 2023-01-05
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Yoshiki Higaの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3713号
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学位記番号 | 甲口第492号
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学位授与年月日 | 2023-03-23
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学位名 |
博士(歯学)
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学位授与機関 |
徳島大学
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部局 |
歯学系
病院
医学系
先端酵素学研究所
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