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Article

E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT

1
State key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China
2
National Institute of Biological Sciences (NIBS), Beijing 102206, China
3
Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China
4
Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH 45215, USA
5
Department of Animal Science, Texas A&M University, College Station, TX 77843, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 1024; https://doi.org/10.3390/cells9041024
Received: 1 March 2020 / Revised: 25 March 2020 / Accepted: 7 April 2020 / Published: 21 April 2020
Wnt/β-catenin is a crucial repressor of adipogenesis. We have shown that E2 promoter binding factor 1 (E2F1) suppresses Wnt/β-catenin activity through transactivation of β-catenin interacting protein 1 (CTNNBIP1), also known as inhibitor of β-catenin and TCF4 (ICAT) in human colorectal cancers. However, it remains unknown whether ICAT is required for E2F1 to promote differentiation by inhibiting β-catenin activity in pre-adipocytes. In the present study, we found that 1-methyl-3-isobutylxanthine, dexamethasone, and insulin (MDI)-induced differentiation and lipid accumulation in 3T3-L1 pre-adipocytes was reversed by activation of β-catenin triggered by CHIR99021, a GSK3β inhibitor. Intriguingly, we observed a reduced protein level of E2F1 and ICAT at a later stage of pre-adipocytes differentiation. Importantly, overexpression of ICAT in 3T3-L1 pre-adipocytes markedly promote the adipogenesis and partially reversed the inhibitory effect of CHIR99021 on MDI-induced adipogenesis and lipid accumulation by regulating adipogenic regulators and Wnt/β-catenin targets. Moreover, pre-adipocytes differentiation induced by MDI were markedly inhibited in siE2F1 or siICAT transfected 3T3-L1 cells. Gene silencing of ICAT in the E2F1 overexpressed adipocytes also inhibited the adipogenesis. These data indicated that E2F1 is a metabolic regulator with an ability to promote pre-adipocyte differentiation by activating ICAT, therefore represses Wnt/β-catenin activity in 3T3-L1 cells. We also demonstrated that ICAT overexpression did not affect oleic acid-induced lipid accumulation at the surface of Hela and HepG2 cells. In conclusion, we show that E2F1 is a critical regulator with an ability to promote differentiation and adipogenesis by activating ICAT in pre-adipocytes. View Full-Text
Keywords: adipogenesis; differentiation; E2F1; ICAT; Wnt/β-catenin; 3T3-L1 adipogenesis; differentiation; E2F1; ICAT; Wnt/β-catenin; 3T3-L1
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MDPI and ACS Style

Chen, J.; Yang, Y.; Li, S.; Yang, Y.; Dai, Z.; Wang, F.; Wu, Z.; Tso, P.; Wu, G. E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT. Cells 2020, 9, 1024. https://doi.org/10.3390/cells9041024

AMA Style

Chen J, Yang Y, Li S, Yang Y, Dai Z, Wang F, Wu Z, Tso P, Wu G. E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT. Cells. 2020; 9(4):1024. https://doi.org/10.3390/cells9041024

Chicago/Turabian Style

Chen, Jingqing, Yuchen Yang, Shuai Li, Ying Yang, Zhaolai Dai, Fengchao Wang, Zhenlong Wu, Patrick Tso, and Guoyao Wu. 2020. "E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT" Cells 9, no. 4: 1024. https://doi.org/10.3390/cells9041024

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