title: Widdrol blocks 3T3-L1 preadipocytes growth and differentiation due to inhibition of mitotic clonal expansion.
abstract: Adipocyte differentiation is strongly associated with obesity, which causes metabolic disorders. In this study, we investigated the inhibitory effects of widdrol on 3T3- L1 preadipocyte growth and differentiation. Widdrol decreased lipid droplet accumulation and down-regulated adipogenic transcription factors such as C/EBPalpha, C/EBPbeta, and PPARgamma. Widdrol blocked preadipocyte proliferation and differentiation through the inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor. Cell-cycle analysis clearly indicated that widdrol actively induces cell-cycle arrest at the G1-S phage transition, causing cells to remain in the preadipocyte state. Moreover, widdrol increased p21 expression and inhibited Rb phosphorylation in preadipocyte incubated in a hormone medium. Therefore, these findings clearly suggest that widdrol blocks preadipocyte growth and differentiation through the inhibition of mitotic clonal expansion by p21- and Rb-dependent G1 arrest and can be developed as a potent anti-adipogenic agent for reducing obesity.
authors.affiliation: Department of Biomaterial Control (BK21 program), Dong-Eui University Graduate School, Busan 614-714, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Yun
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Jeong
authors.forename: Hyang-Hwa
authors.initials: HH
authors.lastname: Ji
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Nam
authors.forename: Eun Woo
authors.initials: EW
authors.lastname: Lee
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001567:Benzocycloheptenes / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000187:drug effects
chemical_list: D001567:Benzocycloheptenes; D006131:Growth Inhibitors; C078670:widdrol