Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome-proliferator-activated receptor gamma (PPARgamma)

Biol Cell. 2009 Sep 23;102(1):1-12. doi: 10.1042/BC20090070.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Carbazoles / pharmacology
  • Cell Differentiation*
  • Cells, Cultured
  • Chromans / pharmacology
  • Cyclic S-Oxides / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Mice
  • PPAR gamma / metabolism*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism*
  • Thiazolidinediones / pharmacology
  • Troglitazone
  • Tyrphostins / pharmacology

Substances

  • Carbazoles
  • Chromans
  • Cyclic S-Oxides
  • Enzyme Inhibitors
  • PPAR gamma
  • STAT3 Transcription Factor
  • Thiazolidinediones
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • stattic
  • Go 6976
  • Troglitazone