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


CONCLUSIONS
These data indicate that STAT3 functions as a critical factor for adipogenesis via a mechanism involving the PPARgamma activation pathway.
Wang
Dongmei
D
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
Zhou
Yiran
Y
Lei
Weiwei
W
Zhang
Kehua
K
Shi
Jian
J
Hu
Ying
Y
Shu
Guangwen
G
Song
Jianguo
J
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003499:Cyclic S-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D020032:Tyrphostins / Q000494:pharmacology
D002227:Carbazoles; D002839:Chromans; D003499:Cyclic S-Oxides; D004791:Enzyme Inhibitors; D047495:PPAR gamma; D050796:STAT3 Transcription Factor; D045162:Thiazolidinediones; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C517409:stattic; C081021:Go 6976; D000077288:Troglitazone