RAPAMYCIN INHIBITS CLONAL EXPANSION AND ADIPOGENIC DIFFERENTIATION OF3T3-L1 CELLS

The temporal expression profile of this protein, designated FK506-bind ing protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones, Havi ng observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs-cyclosporin A, FK506, and rap amycin-on the terminal-differentiation process. Adipocyte conversion w as not affected by either cyclosporin A or FK506 and yet was significa ntly reduced by rapamycin at drug concentrations as low as 10 nM. Clon al expansion was impeded in drug-treated cultures, as was the accumula tion of cytoplasmic lipid droplets normally seen late during different iation. Rapamycin treatment likewise inhibited the expression of CCAAT /enhancer binding protein alpha a transcription factor required for 3T 3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory e vent was mediated by an immunophilin-rapamycin complex.