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ID 119349
Title Alternative
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
Author
Mori, Yuki Tokushima University
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
Ohnishi, Kohta Tokushima University
Keywords
Atra
Autophagy
Lipolysis
Aged
ALDH1A1
Content Type
Thesis or Dissertation
Description
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.
Journal Title
The Journal of Nutritional Biochemistry
ISSN
09552863
18734847
NCID
AA10748929
AA11533735
Publisher
Elsevier
Volume
126
Start Page
109589
Published Date
2024-02-01
Remark
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。
Rights
This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3808号
Diploma Number
甲栄第307号
Granted Date
2024-03-22
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences