Activation of signal transducer and activator of transcription-3 during proliferative phases of 3T3-L1 adipogenesis.

Signal transducer and activator of transcription-3 (STAT3) is abundantly expressed in preadipocytes and adipocytes, but little is known about its activation status or functional role during adipogenesis. In this report we investigate STAT3 activation in 3T3-L1 preadipocytes before and after differentiation into adipocytes. STAT3 was highly tyrosine phosphorylated and bound to DNA in proliferating preadipocytes, but not in growth-arrested preadipocytes or adipocytes. In growth-arrested confluent preadipocytes, induction of differentiation with methylisobutylxanthine, dexamethasone, and high dose insulin led to a delayed, but prolonged (3-day), increase in STAT3 tyrosine phosphorylation. This increase in STAT3 phosphorylation coincided temporally with postconfluent preadipocyte mitotic clonal expansion. Insulin and methylisobutylxanthine alone, but not dexamethasone, induced STAT3 tyrosine phosphorylation in postconfluent cells. Diminution of endogenous STAT3 expression by antisense morpholino oligonucleotides significantly decreased preconfluent preadipocyte proliferation. Collectively, these findings suggest a regulatory role for STAT3 during the proliferative phases of adipogenesis.