INHIBITION OF INCREASES OF TRANSCRIPTION FACTOR MESSENGER-RNAS DURINGDIFFERENTIATION OF PRIMARY RAT ADIPOCYTES BY IN-VIVO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) TREATMENT

Understanding the differentiation pathway of adipocytes is an importan t first step for controlling human and animal fat deposition. Although many studies have been done on adipogenesis, most have utilized estab lished cell lines rather than isolated primary cells. We have studied primary preadipocyte differentiation to determine whether the cell lin es reflect the situation in vivo. In this study, mRNA of several trans cription factors and adipocyte-related enzymes, isolated from cultured differentiating primary rat inguinal and epididymal cells, followed t he same pattern of change during differentiation as seen in differenti ating 3T3-L1 cells. As the cells differentiated, mRNA for C/EBP alpha, PPAR gamma 2, aP2 and lipoprotein lipase (LPL) increased, C/EBP beta decreased and CHOP remained at a low level. Previously we have shown t hat 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 treat ment in vivo also inhibited the increase of mRNA for the PPAR gamma 2, aP2 and C/EBP alpha during differentiation of the isolated preadipocy tes. C/EBP beta and CHOP mRNAs were unaffected. Due to the similarity of changes of the transcription factor mRNAs for primary and 3T3-L1 ce lls during differentiation and after TCDD treatment, 3T3-L1 cells appe ar to provide a good model for more clearly defining the route of adip ogenesis and TCDD inhibition. (C) 1997 Elsevier Science Ireland Ltd.