Inhibition of increases of transcription factor mRNAs during differentiation of primary rat adipocytes by in vivo 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment.

Understanding the differentiation pathway of adipocytes is an important first step for controlling human and animal fat deposition. Although many studies have been done on adipogenesis, most have utilized established cell lines rather than isolated primary cells. We have studied primary preadipocyte differentiation to determine whether the cell lines reflect the situation in vivo. In this study, mRNA of several transcription factors and adipocyte-related enzymes, isolated from cultured differentiating primary rat inguinal and epididymal cells, followed the same pattern of change during differentiation as seen in differentiating 3T3-L1 cells. As the cells differentiated, mRNA for C/EBPalpha, PPARgamma2, aP2 and lipoprotein lipase (LPL) increased, C/EBPbeta decreased and CHOP remained at a low level. Previously we have shown that in vivo treatment with TCDD (2,3,7,8- tetrachlorodibenzo-p-dioxin) inhibits in vitro adipogenesis and the increase of mRNAs for glycerol-3-phosphate dehydrogenase and LPL (Tox. Lett. 84:55, 1996). TCDD treatment in vivo also inhibited the increase of mRNA for the PPARgamma2, aP2 and C/EBPbeta during differentiation of the isolated preadipocytes. C/EBPbeta and CHOP mRNAs were unaffected. Due to the similarity of changes of the transcription factor mRNAs for primary and 3T3-LI cells during differentiation and after TCDD treatment, 3T3-L1 cells appear to provide a good model for more clearly defining the route of adipogenesis and TCDD inhibition.