Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway. Issue 1 (27th November 2019)

• Record Type: Journal Article
• Authors: Lee, Yu Seol; Park, Jeong Su; Lee, Da Hyun; Han, Jisu; Bae, Soo Han
• Is Part Of: FASEB journal. Volume 34:Issue 1(2020)
• Page Start: 898
• Page End: 911
• Publication Date: 2019-11-27
• Subjects: adipogenesis -- AMPK -- ezetimibe -- mitotic clonal expansion -- obesity; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201901569R
• Languages: English
• ISSNs: 0892-6638

Abstract

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.