Abstract
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)α without altering the expression patterns of C/EBPβ or C/EBPδ along the differentiation. Supershift analysis showed that DNA-binding capacity of C/EBPα was affected most by endrin treatment. Endrin also caused a decrease in the elevation of the adipogenic factor peroxisome proliferator-activated receptor (PPAR)γ elicited by the adipogenic inducers. However, the cotreatment with troglitazone, a thiazolidinedione known to activate PPARγ, did not suppress the antiadipogenic action of endrin, indicating that its direct action site is not PPARγ receptor. Endrin also altered the pattern of activation of nuclear factor-κB, a factor activated by 12-O-tetradecanoylphorbol-13-acetate and tumor necrosis factor-α, which are known to interfere with adipocyte differentiation. Thus, endrin inhibited the normal decrease in nuclear factor-κB-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/EBPα.
Footnotes
- Received October 23, 1998.
- Accepted April 15, 1999.
-
Send reprint requests to: Dr. Fumio Matsumura, Department of Environmental Toxicology, University of California, Davis, CA 95616. E-mail: fmatsumura{at}ucdavis.edu
-
This work was supported by Research Grants ES03575 and ES05707 from the National Institute of Environmental Health Sciences, California Agricultural Experimental Station, Grant HHHERP from Hawaii Heptachlor Research and Education Foundation, and a postdoctoral fellowship from the Ministerio de Educación y Cultura of Spain (to M.J.M.-A.). A portion of this work was previously presented in the 37th Annual Meeting of the Society of Toxicology (Seattle, 1998).
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|