Differentiation of 3T3-F442A cells into adipocytes is inhibited by retinoic acid.

Retinoic acid at a concentration higher than 10(-6) M inhibited adipose conversion of 3T3-F442A cells in surface cultures. Since cells treated with 10(-5) M of the vitamin A analogue and the non-treated cells showed the same capacity to form colonies when seeded at low density, adipose conversion was not inhibited by a general toxic action of the retinoid. The inhibition produced was accompanied by changes in cell shape; adipose morphology was absent in retinoic acid treated cells, and they were more elongated and flattened without piling up. Adipose conversion of 3T3-F442A in Methocel suspended cultures was also inhibited by retinoic acid, suggesting the inhibition exerted by this compound was not related to the changes observed in cell shape. The inhibitory action of retinoic acid is manifested only when the cultures are treated before differentiation takes place; if the retinoid was added after some early events of adipose conversion, differentiation was not blocked. The inhibition was reversed when the drug was removed from the cultures and they were further incubated in adipogenic medium; incubation in medium without adipogenic factor did not permit reversion. On the other hand, vitamin A depleted serum showed a higher capacity to support adipose conversion than non-depleted serum. It is concluded that this vitamin A analogue blocks some early events before the cells undergo the commitment to differentiate into adipocytes.