title: The forkhead transcription factor FOXO1 stimulates the expression of the adipocyte resistin gene.
abstract: Resistin is known as an adipocyte-specific hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by transcriptional factors, but the possible role of forkhead transcription factor FOXO1 in regulating resistin gene expression is still unknown. Using 3T3 fibroblast and C3H10T1/2 and 3T3-L1 adipocytes, we found that transient overexpression of a non-phosphorylatable, constitutively active FOXO1, but not the wild type of FOXO1 or a DNA binding-deficient FOXO1, activated resistin promoter-directed luciferase expression. However, transient overexpression of a dominant-negative FOXO1 inactivated resistin promoter activity and reduced resistin mRNA expression. These observations indicate that the action of FOXO1 on resistin gene expression requires the activation of FOXO1 and that the effect of FOXO1 depends on the phosphorylation and dephosphorylation of FOXO1. The FOXO1 protein target sites on the resistin promoter were localized to the proximal -3545 to -787bp of 5'-flanking region of the resistin promoter. A chromatin immunoprecipitation assay also showed that FOXO1 bound the resistin promoter at nucleotide regions of -1539 to -1366bp and -1016 to -835bp, but not at the regions of -795 to -632bp. Results of this study suggest that FOXO1 transcription factor likely activates the expression of adipocyte resistin gene via direct association with the upstream resistin promoter.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors.forename: Shu-Ya
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Joint Laboratory, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Department of Joint Laboratory, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Hang-Seng
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Veterans General Hospital, Taipei, Taiwan.
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.affiliation: Department of Bioscience Technology, Chung-Yuan Christian University, Jhongli, Taoyuan, Taiwan.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors.forename: Meng-Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Ku
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors.forename: Hsin-Huei
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Entomology, National Taiwan University, Taipei, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Huang
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan. Electronic address: ykao@cc.ncu.edu.tw.
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D052243:Resistin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; D008156:Luciferases
keywords: Adipocyte; FOXO; Preadipocyte; Resistin; Transcription factor