INDUCTION OF THE NUCLEAR ORPHAN RECEPTOR ROR-GAMMA 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, ROR alpha and ROR gamma mRNA were up-regulated durin g adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, where as ROR beta mRNA could not be detected, The induction of ROR alpha and ROR gamma mRNA succeeded the induction of peroxisome proliferator-act ivated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in a P2 and lipoprotein lipase mRNA. Like the expression of PPAR gamma and aP2, the induction of ROR gamma mRNA was repressed by tumor necrosis f actor alpha and transforming growth factor beta. The induction of adip ogenesis by prostaglandin D2 and two thiazolidinediones in the multipo tent stem cells C3H10T1/2 was also accompanied by an induction in ROR gamma mRNA, In contrast to parental cells, clofibrate induces adipogen esis and ROR alpha and ROR gamma mRNA in BALB/ c3T3 cells that ectopic ally express PPAR gamma, ROR gamma mediates its effect on transcriptio n through specific response elements. Cotransfection of ROR alpha or R OR gamma and (ROR gamma response element)(4)-chloramphenicol acetyltra nsferase into preadipocyte D1 cells induced transactivation of chloram phenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes, The nuclear orphan receptor Rev-ErbA alpha, which did not exhibit transactivation function, was able to inhibit transactivation by ROR gamma at two diff erent levels. Our results show that ROR gamma is induced during adipoc yte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for ROR gamma in the regulatio n of gene expression during this differentiation process.