title: Role of Krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis.
abstract: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles during cell differentiation and development in mammals. We have now shown by microarray analysis that expression of the KLF15 gene is markedly up-regulated during the differentiation of 3T3-L1 preadipocytes into adipocytes. Inhibition of the function of KLF15, either by expression of a dominant negative mutant or by RNA interference, both reduced the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and blocked adipogenesis in 3T3-L1 preadipocytes exposed to inducers of adipocyte differentiation. However, the dominant negative mutant of KLF15 did not affect the expression of CCAAT/enhancer-binding protein beta (C/EBPbeta) elicited by inducers of differentiation in 3T3-L1 preadipocytes. In addition, ectopic expression of KLF15 in NIH 3T3 or C2C12 cells triggered both lipid accumulation and the expression of PPARgamma in the presence of inducers of adipocyte differentiation. Ectopic expression of C/EBPbeta, C/EBPdelta, or C/EBPalpha in NIH 3T3 cells also elicited the expression of KLF15 in the presence of inducers of adipocyte differentiation. Moreover, KLF15 and C/EBPalpha acted synergistically to increase the activity of the PPARgamma2 gene promoter in 3T3-L1 adipocytes. Our observations thus demonstrate that KLF15 plays an essential role in adipogenesis in 3T3-L1 cells through its regulation of PPAR gamma expression.
authors.affiliation: Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Iguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Gomi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuki
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D005799:Genes, Dominant; D005822:Genetic Vectors; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D012333:RNA, Messenger; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D008156:Luciferases