The complex network of adipogenic transcription factors regulates adipocyte differentiation, obesity, and insulin resistance. Modulator recognition factor (Mrf) 2 knockout mice exhibit defects in fat accumulation and are protected from diet-induced obesity, suggesting that Mrf2 deficiency affects adipogenesis. Here, we report that the gene expressions of the 2 isoforms of the transcription factors Mrf2, Mrf2 alpha, and Mrf2 beta, were induced upon adipogenesis in 3T3-L1 cells. Mrf2 mRNA expression was sensitive to stimulation by insulin, dexamethasone, and TNF-alpha in 3T3-L1 preadipocytes and differentiated adipocytes. Down-regulation of Mrf2 alpha and Mrf2 beta gene expressions induced by small interfering RNAs increased the mRNA expression of leptin. These results indicate that Mrf2 can be a potential regulator of adipocyte differentiation and a potential repressor of leptin. (c) 2007 Elsevier Inc. All rights reserved.