The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2

• Material Type: 博士論文
• Title: The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2
• Author/Editor: Higa, Yoshiki; Hiasa, Masahiro; Tenshin, Hirofumi; Nakaue, Emiko; Tanaka, Mariko; Kim, Sooha; Nakagawa, Motosumi; Shimizu, So; Tanimoto, Kotaro; Teramachi, Jumpei; Harada, Takeshi; Oda, Asuka; Oura, Masahiro; Sogabe, Kimiko; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Endo, Itsuro; Matsumoto, Toshio; Tanaka, Eiji; Abe, Masahiro
• Author Heading: Higa, Yoshiki; Hiasa, Masahiro; Tenshin, Hirofumi; Nakaue, Emiko; Tanaka, Mariko; Kim, Sooha; Nakagawa, Motosumi; Shimizu, So; Tanimoto, Kotaro; Teramachi, Jumpei; Harada, Takeshi; Oda, Asuka; Oura, Masahiro; Sogabe, Kimiko; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Endo, Itsuro; Matsumoto, Toshio; Tanaka, Eiji; Abe, Masahiro
• Publication, Distribution, etc.: MDPI
• Publication Date: 2023-01-05
• Publication Date (W3CDTF): 2023-01-05
• Alternative Title: 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
• Periodical title: Antioxidants
• No. or year of volume/issue: 12 1
• Volume: 12
• Issue: 1
• Pages: 133-
• ISSN (Periodical Title): ISSN : 2076-3921
• Degree grantor/type: 徳島大学
• Date Granted: 2023-03-23
• Dissertation Number: 甲第3713号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: obesity; adipocytic differentiation; reactive oxygen species (ROS); xanthine oxidoreductase (XOR); febuxostat; Nrf2; Keap1
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: インターネット公開
• Rights (production): 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/).
• Related Material (DOI): 10.3390/antiox12010133
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/118313/20230620172738459521/k3713_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118313/20230620172738594029/k3713_review.pdf fulltext

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