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Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK-mTORC1 pathway

Authors
 Yu Seol Lee  ;  Jeong Su Park  ;  Da Hyun Lee  ;  Jisu Han  ;  Soo Han Bae 
Citation
 FASEB JOURNAL, Vol.34(1) : 898-911, 2020 
Journal Title
 FASEB JOURNAL 
ISSN
 0892-6638 
Issue Date
2020
Keywords
AMPK ; adipogenesis ; ezetimibe ; mitotic clonal expansion ; obesity
Abstract
Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet-induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti-adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator-activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe-mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis-related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe-mediated inhibition of adipogenesis is dependent on the AMPK-mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.
Full Text
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201901569R
DOI
10.1096/fj.201901569R
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Jeong Su(박정수) ORCID logo https://orcid.org/0000-0003-4551-4294
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175257
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