Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor α mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ER(T2)) in adipocytes

Retinoid X receptor α (RXRα) is involved in multiple signaling pathways, as a heterodimeric partner of several nuclear receptors. To investigate its function in energy homeostasis, we have selectively ablated the RXRα gene in adipocytes of 4-week-old transgenic mice by using the tamoxifen-inducible Cre-ER(T2) recombination system. Mice lacking RXRα in adipocytes were resistant to dietary and chemically induced obesity and impaired in fasting-induced lipolysis. Our results also indicate that RXRα is involved in adipocyte differentiation. Thus, our data demonstrate the feasibility of adipocyte-selective temporally controlled gene engineering and reveal a central role of RXRα in adipogenesis, probably as a heterodimeric partner for peroxisome proliferator-activated receptor γ.