ID | 119349 |
タイトル別表記 | 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
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著者 |
森, 優樹
徳島大学大学院医科栄養学研究科(医科栄養学専攻)
Yoshida-Shimizu, Risa
Tokushima University
Aoyagi, Saki
Tokushima University
Adachi, Yuichiro
Tokushima University
Nguyen, Anh The
Tokushima University
Maruyama, Yusuke
Tokushima University
Okumura, Yosuke
Tokushima University
Sakai, Maiko
Tokushima University
大西, 康太
Tokushima University
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キーワード | Atra
Autophagy
Lipolysis
Aged
ALDH1A1
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資料タイプ |
学位論文
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抄録 | 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.
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掲載誌名 |
The Journal of Nutritional Biochemistry
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ISSN | 09552863
18734847
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cat書誌ID | AA10748929
AA11533735
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出版者 | Elsevier
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巻 | 126
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開始ページ | 109589
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発行日 | 2024-02-01
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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Yuki Mori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 is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/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3808号
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学位記番号 | 甲栄第307号
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学位授与年月日 | 2024-03-22
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学位名 |
博士(栄養学)
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学位授与機関 |
徳島大学
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部局 |
医学系
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