All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes

• Material Type: 博士論文
• Title: All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes
• Author/Editor: Mori, Yuki; Masuda, Masashi; Yoshida-Shimizu, Risa; Aoyagi, Saki; Adachi, Yuichiro; Nguyen, Anh The; Maruyama, Yusuke; Okumura, Yosuke; Kamei, Yuki; Sakai, Maiko; Ohnishi, Kohta; Ohminami, Hirokazu; Taketani, Yutaka
• Author Heading: Mori, Yuki; Masuda, Masashi; Yoshida-Shimizu, Risa; Aoyagi, Saki; Adachi, Yuichiro; Nguyen, Anh The; Maruyama, Yusuke; Okumura, Yosuke; Kamei, Yuki; Sakai, Maiko; Ohnishi, Kohta; Ohminami, Hirokazu; Taketani, Yutaka
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2024-02-01
• Publication Date (W3CDTF): 2024-02-01
• Alternative Title: 脂肪細胞においてall-transレチノイン酸はAMPK-Beclin1シグナリング経路の活性化を介したリポファジーの誘導やRubicon発現の減少を引き起こす
• Periodical title: The Journal of Nutritional Biochemistry
• No. or year of volume/issue: 126
• Volume: 126
• Pages: 109589-
• ISSN (Periodical Title): ISSN : 0955-2863; ISSN : 1873-4847
• Degree grantor/type: 徳島大学
• Date Granted: 2024-03-22
• Dissertation Number: 甲第3808号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Subject Heading: Atra; Autophagy; Lipolysis; Aged; ALDH1A1
• Target Audience: 一般
• Note (General): Lipophagy is defined as a lipolysis pathway that degrades lipid droplet (LD) via autophagy. All-trans retinoic acid (atRA), a metabolite of vitamin A, stimulates lipolysis through hormone-sensitive lipase and β-oxidation. However, the regulation of lipolysis by atRA-induced autophagy in adipocytes remains unclear. In this study, we investigated the effect of atRA on autophagy in epididymal fat of mice and the molecular mechanisms of autophagy in 3T3-L1 adipocytes. Western blotting showed that atRA decreased the expression of p62, a cargo receptor for autophagic degradation, and increased the expression of the lipidated LC3B (LC3B-II), an autophagy marker, in epididymal fat. Next, we confirmed that atRA increased autophagic flux in differentiated 3T3-L1 cells using the GFP-LC3-RFP-LC3ΔG probe. Immunofluorescent staining revealed that the colocalization of LC3B with perilipin increased in differentiated 3T3-L1 cells treated with atRA. The knockdown of Atg5, an essential gene in autophagy induction, partly suppressed the atRA-induced release of non-esterified fatty acid (NEFA) from LDs in differentiated 3T3-L1 cells. atRA time-dependently elicited the phosphorylation of AMPK and Beclin1, autophagy-inducing factors, in mature 3T3-L1 adipocytes. Inversely, atRA decreased the protein expression of Rubicon, an autophagy repressor, in differentiated 3T3-L1 cells and epididymal fat. Interestingly, the expression of ALDH1A1, atRA-synthesizing enzymes, increased in epididymal fat with decreased protein expression of Rubicon in aged mice. These results suggest that atRA may partially induce lipolysis through lipophagy by activating the AMPK-Beclin1 signaling pathway in the adipocytes and increased atRA levels may contribute to decreased Rubicon expression in the epididymal fat of aged mice.
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/ )
• Related Material (DOI): 10.1016/j.jnutbio.2024.109589
• 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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