Leptin activates Stat3, Stat1 and AP-1 in mouse adipose tissue.
Intraperitoneal leptin administration to wild-type and ob/ob mice caused a prompt activation of Stat1 and Stat3, the former to a lesser extent, in epididymal adipose tissue. Immunoblot experiments showed that tyrosine phosphorylation of Stat3 increased in total cellular extracts and that the phosphorylated protein translocated into the nucleus upon leptin treatment. Tyrosine phosphorylation and nuclear translocation of Stat1 were evident only in ob/ob mice. Gel shift and supershift analyses showed that leptin activated sis-inducible element (SIE) binding activity of adipose nuclear extracts, with Stat3 homodimer as the predominant complex. Stat1/3 heterodimers and Stat1 homodimers take part as well in the response in wild-type and ob/ob mice, although to a lesser degree. AP-1 binding activity was also induced in adipose tissue by in vivo leptin treatment with a time course that suggests a post-transcriptional inductive mechanism. This effect was greater in the ob/ob than in wild-type mice. Our data indicate that leptin operates in vivo directly on adipose tissue by triggering responses that modulate gene expression.
Bendinelli
P
P
Istituto di Patologia Generale, Università degli Studi di Milano, Centro di Studio sulla Patologia Cellulare del C.N.R., Via Mangiagalli 31, 20133, Milan, Italy.
Maroni
P
P
Pecori Giraldi
F
F
Piccoletti
R
R
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002457:Cell Extracts; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D015151:Immunoblotting; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010766:Phosphorylation; D020218:Response Elements; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D020738:Leptin; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D004247:DNA