Autocrine control of adipose cell differentiation by prostacyclin and PGF2α

Abstract

The mitogenic-adipogenic effect exerted by arachidonic acid, which leads to terminal differentiation of Ob1771 mouse preadipocytes, has been shown to be (i) blocked by cyclooxygenase inhibitors, (ii) mimicked by a stable analogue of prostacyclin (carboprostacyclin) and (iii) potentiated by PGF2α. Since these prostanoids are known to be synthesized and secreted by preadipocytes, we have proposed that both prostacyclin as the key mediator and PGF2α as a modulator control the expression of terminal events of adipose conversion by means of an autocrine mechanism (Gaillard, D. et al. and Negrel, R. et al. Biochem. J. (1989) 257, 389–397 and 399–405). In order to test this hypothesis, the release of prostacyclin, characterized under the form of its stable degradation product 6-keto-PGF1α, and that of PGF2α have been studied in the culture medium of Ob1771 cells. A striking increase in the release of 6-keto-PGF1α and to a minor degree of PGF2α was observed when cells were exposed to arachidonic acids as shown by using [3H]arachidonic acid prelabelled cells or by radio-immunoassays. Since antagonists of PGF2α and PGI2 receptors were not available, specific antibodies directed against PGF2α and 6β-PGI1, another stable analogue of prostacyclin, were added as neutralizing agents in the culture medium. These antibodies were able to counteract the mitogenic-adipogenic effect of arachidonic acid. Prostacyclin and PGF2α thus appear as autocrine mediators in the process of adipose conversion.