Vol. 56, Issue 1, 91-101, July 1999

Endrin Inhibits Adipocyte Differentiation by Selectively Altering Expression Pattern of CCAAT/Enhancer Binding Protein- in 3T3-L1 Cells

Maria J. Moreno-Aliaga and Fumio Matsumura

Department of Environmental Toxicology and the Center for Environmental Health Sciences, University of California, Davis, California

The effects of selected chlorinated cyclodiene pesticides on the adipocyte differentiation process were examined using the 3T3-L1 adipocyte model in vitro. Endrin was found to cause a dose-dependent inhibition of adipocyte differentiation in 3T3-L1 cells. Aldrin and dieldrin were less potent than endrin in interfering with the adipogenic process. Endrin's inhibitory effect was effective only when the pesticide was present in the medium during the first 48 h after exposure of 3T3-L1 cells to adipogenic inducers. Immunoblots analysis revealed that endrin caused a dose-dependent, selective inhibition of the intracellular levels of CCAAT enhancer binding protein (C/EBP) without altering the expression patterns of C/EBP or C/EBP along the differentiation. Supershift analysis showed that DNA-binding capacity of C/EBP was affected most by endrin treatment. Endrin also caused a decrease in the elevation of the adipogenic factor peroxisome proliferator-activated receptor (PPAR) elicited by the adipogenic inducers. However, the cotreatment with troglitazone, a thiazolidinedione known to activate PPAR, did not suppress the antiadipogenic action of endrin, indicating that its direct action site is not PPAR receptor. Endrin also altered the pattern of activation of nuclear factor-B, a factor activated by 12-O-tetradecanoylphorbol-13-acetate and tumor necrosis factor-, which are known to interfere with adipocyte differentiation. Thus, endrin inhibited the normal decrease in nuclear factor-B-DNA binding observed as cells are acquiring the adipocyte phenotype at a late stage of differentiation. Our results suggest that endrin inhibits adipocyte differentiation through the specific suppression of C/EBP.