title: Identification of Creb3l4 as an essential negative regulator of adipogenesis.
abstract: Understanding the molecular networks that regulate adipogenesis is crucial for combating obesity. However, the identity and molecular actions of negative regulators that regulate the early development of adipocytes remain poorly understood. In this study, we investigated the role of CREB3L4, a member of the CREB3-like family, in the regulation of adiposity. Constitutive overexpression of CREB3L4 resulted in the inhibition of adipocyte differentiation, whereas knockdown of Creb3l4 expression caused differentiation of preadipocytes into mature adipocytes, bypassing the mitotic clonal expansion step. In 3T3-L1 preadipocytes, Creb3l4 knockdown resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ2) and CCAAT/enhancer binding protein (C/EBPα), either by increasing the protein stability of C/EBPβ or by decreasing the expression of GATA3, a negative regulator of PPARγ2 expression. Consequently, increased PPARγ2 and C/EBPα levels induced adipocyte differentiation, even in the presence of minimal hormonal inducer. Thus, it can be speculated that CREB3L4 has a role as gatekeeper, inhibiting adipogenesis in 3T3-L1 preadipocytes. Moreover, adipocytes of Creb3l4-knockout mice showed hyperplasia caused by increased adipogenesis, and exhibited improved glucose tolerance and insulin sensitivity, as compared with littermate wild-type mice. These results raise the possibility that Creb3l4 could be a useful therapeutic target in the fight against obesity and metabolic syndrome.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: T-H
authors.initials: TH
authors.lastname: Kim
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea [2] Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Jo
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nojima
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kim
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea [2] Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Ahn
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics*; D050154:Adiposity / Q000235:genetics; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C453743:Creb3l4 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D047495:PPAR gamma