PMID- 12821652 OWN - NLM STAT- MEDLINE DCOM- 20031117 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 278 IP - 39 DP - 2003 Sep 26 TI - The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation. PG - 37672-80 AB - Rev-Erbalpha (NR1D1) is an orphan nuclear receptor encoded on the opposite strand of the thyroid receptor alpha gene. Rev-Erbalpha mRNA is induced during adipocyte differentiation of 3T3-L1 cells, and its expression is abundant in rat adipose tissue. Peroxisome proliferator-activated receptor gamma (PPARgamma) (NR1C3) is a nuclear receptor controlling adipocyte differentiation and insulin sensitivity. Here we show that Rev-Erbalpha expression is induced by PPARgamma activation with rosiglitazone in rat epididymal and perirenal adipose tissues in vivo as well as in 3T3-L1 adipocytes in vitro. Furthermore, activated PPARgamma induces Rev-Erbalpha promoter activity by binding to the direct repeat (DR)-2 response element Rev-DR2. Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation. FAU - Fontaine, Coralie AU - Fontaine C AD - UR545 INSERM, Departement d'Atherosclerose, 1, rue Calmette, Institut Pasteur de Lille, 59019 Lille, France. FAU - Dubois, Guillaume AU - Dubois G FAU - Duguay, Yannick AU - Duguay Y FAU - Helledie, Torben AU - Helledie T FAU - Vu-Dac, Ngoc AU - Vu-Dac N FAU - Gervois, Philippe AU - Gervois P FAU - Soncin, Fabrice AU - Soncin F FAU - Mandrup, Susanne AU - Mandrup S FAU - Fruchart, Jean-Charles AU - Fruchart JC FAU - Fruchart-Najib, Jamila AU - Fruchart-Najib J FAU - Staels, Bart AU - Staels B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030623 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (DNA-Binding Proteins) RN - 0 (NR1D1 protein, human) RN - 0 (Nr1d1 protein, rat) RN - 0 (Nuclear Receptor Subfamily 1, Group D, Member 1) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) SB - IM MH - Adipocytes/*cytology MH - Animals MH - Binding Sites MH - CCAAT-Enhancer-Binding Protein-alpha/physiology MH - CCAAT-Enhancer-Binding Protein-beta/physiology MH - Cell Differentiation MH - DNA-Binding Proteins/*genetics MH - Dimerization MH - Humans MH - Male MH - Nuclear Receptor Subfamily 1, Group D, Member 1 MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cytoplasmic and Nuclear/*genetics/*physiology MH - Receptors, Retinoic Acid/metabolism MH - Retinoid X Receptors MH - Transcription Factors/metabolism/*physiology MH - Transcription, Genetic EDAT- 2003/06/25 05:00 MHDA- 2003/12/03 05:00 CRDT- 2003/06/25 05:00 PHST- 2003/06/25 05:00 [pubmed] PHST- 2003/12/03 05:00 [medline] PHST- 2003/06/25 05:00 [entrez] AID - S0021-9258(20)83331-6 [pii] AID - 10.1074/jbc.M304664200 [doi] PST - ppublish SO - J Biol Chem. 2003 Sep 26;278(39):37672-80. doi: 10.1074/jbc.M304664200. Epub 2003 Jun 23.