Stimulation of 3T3-L1 adipogenesis by signal transducer and activator of transcription 5.
Signal transducer and activator of transcription 5 (Stat5) mediates signaling of many cytokines and growth factors. Here we show that Stat5 functions as an initial mediator of adipogenesis. The preadipocyte cell line 3T3-L1 undergoes adipocyte differentiation upon appropriate hormonal induction. We found that Stat5A and Stat5B were strongly activated at an early stage of 3T3-L1 differentiation. To investigate physiological roles of Stat5 in adipogenesis, we have constructed 3T3-L1 cell lines in which either an exogenous wild type (wt) or dominant negative (dn) form of Stat5A expression was controlled under the doxycycline-regulatable promoter. Precocious induction of wt-Stat5A in adipocyte differentiation promoted accumulation of triglycerides within the cells. In contrast, induction of dn-Stat5A attenuated lipid accumulation. Northern blot analyses revealed that the expression of proadipogenic transcription factors was influenced in a complementary fashion by ectopic expression of either wt- or dn-Stat5A. Notably, Stat5 regulated expression of peroxisome proliferator-activated receptor-gamma, which plays crucial roles in adipogenesis. We have also generated transgenic mice in which dn-Stat5A is expressed in an adipose tissue-specific fashion and found attenuation of peroxisome proliferator-activated receptor-gamma and of many adipocyte-related genes. These results highlight a novel role of Stat5 in adipocyte differentiation.
Nanbu-Wakao
Rika
R
Helix Research Institute, 1532-3 Yana Kisarazu-shi Chiba, 292-0812 Japan.
Morikawa
Yoshihiro
Y
Matsumura
Itaru
I
Masuho
Yasuhiko
Y
Muramatsu
Masa-Aki
MA
Senba
Emiko
E
Wakao
Hiroshi
H
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D050799:STAT5 Transcription Factor; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D050799:STAT5 Transcription Factor; C497388:Srebf1 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D004318:Doxycycline