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 c alcitriol (1 alpha,25-(OH)(2) vitamin D3 or VD), markedly stimulated t he terminal adipose differentiation of Ob 17 preadipocytes cultured un der standard conditions with fetal calf serum (FCS), and increased the differentiating effect of triiodothyronine (T3) reported as a necessa ry adipogenic factor in these cells. Here, we demonstrate, for the fir st time, that VD is an intrinsic strong adipogenic factor for the Ob 1 7 preadipocytes cultured in thyroid hormone-deprived medium (adipogeni c 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 coad dition of either T3, or arachidonic acid, two agents which also bear p roper adipogenic properties. The efficient concentration ranges of oth er vitamin D3 metabolites suggest a mediation through the VD nuclear r eceptor (VDR). An expression of the VDR gene is here demonstrated in t he Ob 17 cells, and evidence is given that VDR mRNA level increased du ring 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 d epending on the availability of their respective ligands. The existenc e of an interplay between these receptors in exerting their adipogenic action is suggested. (C) 1997 Academic Press.