The NR4A family of orphan nuclear receptors are not required for adipogenesis

Nuclear hormone receptors of the NR4A subfamily are rapidly induced during the early stages of adipogenesis, leading to the speculation that they may have important roles in this process. One of the three subfamily members, Nur77 has also been shown to play key roles in energy expenditure and lipolysis in skeletal muscle and in the control of hepatic gluconeogenesis. We, therefore, examined the role of NR4A factors in adipogenesis using the well-characterized 3T3-L1 preadipocyte model. Inhibition of Nur77 expression using siRNA did not affect induction of adipogenic genes, nor the accumulation of lipid. To inhibit the activity of all the three NR4A family members, we generated preadipocytes stably expressing a well-characterized dominant-negative Nur77 ( DN-Nur77), known to block the function of the other NR4A factors, Nurr1 and Nor1, as well as Nur77. While the increased NR4A activity observed following adipogenic induction was completely abolished in these cells, DN-Nur77 expression did not affect the expression of genes characteristic of terminally differentiated adipocytes and had no impact on lipid accumulation in these cells. Thus, while members of the NR4A subfamily of nuclear receptors may have important metabolic roles in skeletal muscle and liver, we demonstrate that they are dispensable for normal adipocyte development.