Transient expression of c-erbAbeta1 messenger ribonucleic acid and beta1 thyroid hormone receptor early in adipogenesis of Ob 17 cells.

In the murine Ob 17 preadipocyte cell line, the thyroid hormone T3 is an adipogenic factor necessary at an early stage for differentiation into adipocyte. We demonstrate here that this T3 dependence may involve a transient expression (at both the messenger RNA and the protein levels) of c-ErbA beta-type receptors (T3R), although a large body of T3R remained the product of the c-erbAalpha gene, as previously described. c-ErbAbeta1 (and not beta2) expression emerged significantly at growth arrest, peaked 2 days later, and almost disappeared in maturing adipocytes. This expression is related to the presence of T3, as total deprivation of culture medium from T3 prevented it, and the addition of 1.5 nM T3 to preconfluent cultures was able to restore it. When cells were cultured in the presence of T3 and thus were able to differentiate, the c-erbAbeta peak was accompanied by sequential rapid increases in CAAT/enhancer-binding protein-delta(C/EBPdelta), peroxisome proliferator-activated-gamma receptor (PPARgamma), and C/EBPalpha gene expressions. On the contrary, under thyroid hormone-deprived culture conditions that result in nondifferentiation of the preadipocytes, c-erbAbeta1, PPARgamma, and the large C/EBPalpha expressions were blunted, and a moderate early increase in c-erbAalpha1 transcripts was sustained for a longer period. Addition of T3 to T3-deprived preconfluent cells restored PPARgamma and C/EBPalpha expressions. Taken together, the results highlight the important role of T3 in the adipogenesis of Ob 17 cells through the involvement of both beta1 and alpha1 T3R subtypes.

Calcitriol is a positive effector of adipose differentiation in the OB 17 cell line: relationship with the adipogenic action of triiodothyronine.

In a previous report, we showed that physiological concentrations of calcitriol (1 alpha,25-(OH)2 vitamin D3 or VD), markedly stimulated the terminal adipose differentiation of Ob 17 preadipocytes cultured under standard conditions with fetal calf serum (FCS), and increased the differentiating effect of triiodothyronine (T3) reported as a necessary adipogenic factor in these cells. Here, we demonstrate, for the first time, that VD is an intrinsic strong adipogenic factor for the Ob 17 preadipocytes cultured in thyroid hormone-deprived medium (adipogenic concentrations: 0.025-0.25 nM in the presence of stripped FCS, 1-10 pM under serum-free conditions). VD action was potentiated by the coaddition of either T3, or arachidonic acid, two agents which also bear proper adipogenic properties. The efficient concentration ranges of other vitamin D3 metabolites suggest a mediation through the VD nuclear receptor (VDR). An expression of the VDR gene is here demonstrated in the Ob 17 cells, and evidence is given that VDR mRNA level increased during the differentiation process and that this increase is moderately amplified under long term treatment with adipogenic concentrations of VD. Our results strongly suggest that adipose differentiation is under the control of different closely related nuclear receptors acting at an early preadipocyte step and probably in an interchangeable manner depending on the availability of their respective ligands. The existence of an interplay between these receptors in exerting their adipogenic action is suggested.