title: c-Jun regulates adipocyte differentiation via the KLF15-mediated mode.
abstract: Abnormal adipocyte differentiation is implicated in the development of metabolic disorders such as obesity and type II diabetes. Thus, an in-depth understanding of the molecular mechanisms associated with adipocyte differentiation is the first step in overcoming obesity and its related metabolic diseases. Here, we examined the role of c-Jun as a transcription factor in adipocyte differentiation. c-Jun overexpression in murine 3T3-L1 preadipocytes significantly inhibited adipocyte differentiation. In addition, the expression level of KLF15, an upstream effector of the key adipogenic factors C/EBPα and PPARγ, was decreased upon the ectopic expression of c-Jun. We found that c-Jun inhibited basal and glucocorticoid receptor (GR)-induced promoter activities of KLF15. c-Jun directly bound near the glucocorticoid response element (GRE) sites in the KLF15 promoter and inhibited adjacent promoter occupancies of GR. Furthermore, the restoration of KLF15 expression in 3T3-L1 cells with the stable ectopic expression of c-Jun partially rescued adipocyte differentiation. Our results demonstrate that c-Jun can suppress adipocyte differentiation through the down-regulation of KLF15 at the transcriptional level. This study proposes a novel mechanism by which c-Jun regulates adipocyte differentiation.
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Da Som
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Choi
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
authors.forename: Baek Soo
authors.initials: BS
authors.lastname: Han
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
authors.forename: Won Kon
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea. Electronic address: kjoh80@kribb.re.kr.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Oh
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea. Electronic address: khbae@kribb.re.kr.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
mesh_terms: D041721:3T3-L1 Cells / Q000166:cytology* / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Adipocyte; Differentiation; KLF15; Obesity; c-JUN