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ID 117431
著者
Yoshida-Shimizu, Risa Tokushima University
Mori, Yuki Tokushima University
大西, 康太 Tokushima University|Kyoto Prefectural University
Adachi, Yuichiro Tokushima University
Sakai, Maiko Tokushima University
Kabutoya, Serina Tokushima University
山本, 浩範 Tokushima University|Jin-ai University|University of Fukui KAKEN研究者をさがす
Miyazaki, Makoto University of Colorado Denver
キーワード
Adipose
Obesity
Autophagy
Cell biology
Lipid droplets
Dietary factors
資料タイプ
学術雑誌論文
抄録
Lipophagy, a form of selective autophagy, degrades lipid droplet (LD) in adipose tissue and the liver. The chemotherapeutic isothiocyanate sulforaphane (SFN) contributes to lipolysis through the activation of hormone-sensitive lipase and the browning of white adipocytes. However, the details concerning the regulation of lipolysis in adipocytes by SFN-mediated autophagy remain unclear. In this study, we investigated the effects of SFN on autophagy in the epididymal fat of mice fed a high-fat diet (HFD) or control-fat diet (CFD) and on the molecular mechanisms of autophagy in differentiated 3T3-L1 cells. Western blotting revealed that the protein expression of lipidated LC3 (LC3-II), an autophagic substrate, was induced after 3T3-L1 adipocytes treatment with SFN. In addition, SFN increased the LC3-II protein expression in the epididymal fat of mice fed an HFD. Immunofluorescence showed that the SFN-induced LC3 expression was co-localized with LDs in 3T3-L1 adipocytes and with perilipin, the most abundant adipocyte-specific protein, in adipocytes of mice fed an HFD. Next, we confirmed that SFN activates autophagy flux in differentiated 3T3-L1 cells using the mCherry-EGFP-LC3 and GFP-LC3-RFP-LC3ΔG probe. Furthermore, we examined the induction mechanisms of autophagy by SFN in 3T3-L1 adipocytes using western blotting. ATG5 knockdown partially blocked the SFN-induced release of fatty acids from LDs in mature 3T3-L1 adipocytes. SFN time-dependently elicited the phosphorylation of AMPK, the dephosphorylation of mTOR, and the phosphorylation of ULK1 in differentiated 3T3-L1 cells. Taken together, these results suggest that SFN may provoke lipophagy through AMPK-mTOR-ULK1 pathway signaling, resulting in partial lipolysis of adipocytes.
掲載誌名
The Journal of Nutritional Biochemistry
ISSN
09552863
cat書誌ID
AA10748929
AA11533735
出版者
Elsevier
106
開始ページ
109017
発行日
2022-04-21
権利情報
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
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
著者版フラグ
著者版
部局
医学系