Background information: STAT3 (signal transducer and activator of transcription 3) is an important transcription factor involved in many biological events, including apoptosis, tumorigenesis, angiogenesis and epithelial-to-mesenchymal transition. However, no direct evidence for a role of STAT3 in 3T3-L1 adipocyte differentiation has been reported.
Results: In the present study, we found that rapid activation of STAT3, lasting for more than 48 h, was elicited upon induction of adipogenesis. Both the STAT3-selective inhibitor stattic and the JAK2 (Janus kinase 2)/STAT3-selective inhibitors AG490 and Gö6976 inhibited STAT3 activation, leading to the suppression of adipocyte differentiation. Adipocyte differentiation was also suppressed by STAT3 siRNA (small interfering RNA) or dominant-negative STAT3. Interestingly, the PPARgamma (peroxisome-proliferator-activated receptor gamma) agonist TAZ (troglitazone) abolished the STAT3-inhibitor- and RNAi (RNA interference)-mediated suppression of adipogenesis. However, TAZ treatment had no effect on the stattic- and AG490-mediated down-regulation of STAT3 activation, suggesting that STAT3 regulates adipocyte differentiation through signalling that occurs upstream of PPARgamma.
Conclusion: These data indicate that STAT3 functions as a critical factor for adipogenesis via a mechanism involving the PPARgamma activation pathway.