Inhibition of adipose conversion in 3T3-L2 cells by retinoic acid

The role of retinoic acid in modulating the differentiation of 3T3-L2 fibroblasts into adipocytes has been examined. Results indicate that the retinoid is capable of effectively inhibiting the degree of adipose conversion which is brought about by treatment of preadipocytes with 1-methyl-3-isobutylxanthine plus dexamethasone. MOrphological and enzymatic (fatty acid synthetase activity) expression of the adipose phenotype are both inhibited more than 90% by 10(-6) M retinoic acid. The inhibition is concentration dependent with retinoic acid must be administered simultaneously with the triggering agents to be effective. Exposure of nongrowing preadipocytes to retinoic acid does not alter the ability o the cells to differentiate in response to a subsequent treatment with methylisobutylxanthine plus dexamethasone. Further, the inhibition is reversible. Cultures i which methylisobutylxanthine plus dexamethasone triggered differentiation has been blocked by addition of retinoic acid (10(-6) M) will readily undergo adipose conversion in response to a second treatment with methylisobutylxanthine plus dexamethasone in the absence of the retinoid. Similar inhibition of differentiation was found when cultures were treated with drugs in medium supplemented with either newborn calf serum or fetal calf serum. However, the extent to which methylisobutylxanthine plus dexamethasone are able to promote differentiation in these cells is considerably greater in medium containing fetal calf serum.