Author:

Abstract:

Introduction: Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) belongs to the steroid/thyroid hormone superfamily and may contribute to the pathogenesis of obesity. It has not been established, however, whether its role is pro- or anti-adipogenic. Methods: To clarify its functional role in adipogenesis, we investigated the role of COUP-TFII in in vitro adipocyte differentiation and in in vivo adipogenesis using established mouse models. Results: During differentiation of murine 3T3-F442A preadipocytes, COUP-TFII gene silencing resulted in enhanced differentiation into mature adipocytes, as monitored by Oil Red O staining and expression of adipogenic markers. This could be explained by an inhibitory effect of COUP-TFII on the Notch-Hey1 signaling pathway. Also in vivo, de novo fat pad formation in NUDE mice was significantly stimulated following injection of preadipocytes with COUP-TFII gene silencing as compared to controls. This was evidenced by adipocyte hyperplasia and enhanced expression of adipogenic markers. In a nutritionally induced obesity model in wild-type mice, COUP-TFII expression was negatively correlated with adipose tissue mass. Moreover, expression of COUP-TFII decreased, whereas Hey1 levels were slightly increased in the adipocyte cell fraction of subcutaneous and gonadal adipose tissues of obese mice as compared to mice kept on normal chow. Conclusion: Our in vitro and in vivo data support an anti-adipogenic role of COUP-TFII likely by inhibition of Notch signaling.