Stimulation of 3T3-L1 adipogenesis by signal transducer and activator of transcription 5

Mol Endocrinol. 2002 Jul;16(7):1565-76. doi: 10.1210/mend.16.7.0862.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / physiology*
  • Adipose Tissue / physiology*
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Doxycycline / pharmacology
  • Mice
  • Mice, Transgenic
  • Milk Proteins*
  • Promoter Regions, Genetic / drug effects
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • STAT5 Transcription Factor
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators / drug effects
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Triglycerides / metabolism


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Milk Proteins
  • Receptors, Cytoplasmic and Nuclear
  • STAT5 Transcription Factor
  • Srebf1 protein, mouse
  • Stat5a protein, mouse
  • Stat5b protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators
  • Transcription Factors
  • Triglycerides
  • Doxycycline