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

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 r...

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Veröffentlicht in:The Journal of nutritional biochemistry 2024-04, Vol.126, p.109589, Article 109589
Hauptverfasser: 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
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container_title The Journal of nutritional biochemistry
container_volume 126
creator 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
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. (248/250 words)
doi_str_mv 10.1016/j.jnutbio.2024.109589
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subjects Aged
ALDH1A1
Atra
Autophagy
Lipolysis
title All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes
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