Depletion of Arylhydrocarbon Receptor during Adipose Differentiation in 3T3-L1 Cells

Abstract

Arylhydrocarbon receptor (AhR) is the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Although a physiological ligand for AhR has yet to be identified, several lines of evidence suggest that AhR may play an important role not only in the regulation of xenobiotic metabolism but also in the maintenance of homeostatic functions. When TCDD is administrated in vivo, this compound is primarily deposited in adipose tissue. Therefore, it is critical to know the states of AhR in adipose cells for assessing the expression of toxicities of TCDD and related compounds in vivo. In this report, we examined the levels of AhR protein and its associated protein (Arnt) during the adipose differentiation in 3T3-L1 cells. The level of AhR protein was found to decrease with ongoing adipose differentiation in 3T3-L1 cells. The binding activity to the xenobiotic response element and the cellular response to TCDD were also lowered as a result of adipose differentiation. These results indicate that the depletion of AhR is a novel event associated with adipose differentiation in 3T3-L1 cells and that the magnitude of the depletion of AhR is sufficient for 3T3-L1 cells to lose the functional response to xenobiotics. We also found a population of 3T3-L1 cells which have an adipose differentiation capability in the presence of high doses of TCDD. These cells lack nuclear AhR but not cytoplasmic AhR, suggesting a possible negative role of liganded nuclear AhR in adipose differentiation. The level of the Arnt protein also decreased as a result of the differentiation. However, the pattern of the depletion of the Arnt protein was distinct from that of the AhR protein. The data presented in this study will provide opportunities to carry out studies to better understand the roles of AhR in adipose cells which are the primary targets of TCDD.