Induction of the nuclear orphan receptor RORgamma during adipocyte differentiation of D1 and 3T3-L1 cells.
Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation. RORalpha and RORgamma mRNA were upregulated during adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, whereas RORbeta mRNA could not be detected. The induction of RORalpha and RORgamma mRNA succeeded the induction of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in aP2 and lipoprotein lipase mRNA. Like the expression of PPARgamma and aP2, the induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta. The induction of adipogenesis by prostaglandin D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also accompanied by an induction in RORgamma mRNA. In contrast to parental cells, clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells that ectopically express PPARgamma. RORgamma mediates its effect on transcription through specific response elements. Cotransfection of RORalpha or RORgamma and (RORgamma response element)4-chloramphenicol acetyltransferase into preadipocyte D1 cells induced transactivation of chloramphenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes. The nuclear orphan receptor Rev-ErbAalpha, which did not exhibit transactivation function, was able to inhibit transactivation by RORgamma at two different levels. Our results show that RORgamma is induced during adipocyte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for RORgamma in the regulation of gene expression during this differentiation process.
Austin
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Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
Medvedev
A
A
Yan
Z H
ZH
Adachi
H
H
Hirose
T
T
Jetten
A M
AM
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002460:Cell Line; D002994:Clofibrate / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D005347:Fibroblasts; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D015230:Prostaglandin D2 / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013234:Stem Cells; D013844:Thiazoles / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C064353:NR1D1 protein, human; C498262:Nr1d1 protein, mouse; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011506:Proteins; D012333:RNA, Messenger; C539738:RORA protein, human; C539900:RORC protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D013844:Thiazoles; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase; D002994:Clofibrate; D015230:Prostaglandin D2