Effects of leukemia inhibitory factor on 3T3-L1 adipocytes.
Leukemia inhibitory factor (LIF) is a member of the gp130 cytokine family and signals through the receptor complex of gp130 and the LIF receptor (LIFR) to activate the JAK/STAT signaling cascade. Since LIF activates STATs 1 and 3 in adipocytes, we examined the effects of LIF on 3T3-L1 adipocytes. Our studies clearly demonstrate that LIF treatment had minimal effects on adipocyte differentiation as judged by marker gene expression, but did inhibit triacylglyceride (TAG) accumulation during adipogenesis. Acute treatment with LIF resulted in increased expression of suppressors of cytokine signaling-3 (SOCS3) and CCAAT/enhancer-binding protein-delta (C/EBPdelta) mRNA in 3T3-L1 adipocytes. Moreover, the upregulation of C/EBPdelta correlated with binding to three sites in the C/EBPdelta promoter by LIF-activated protein complexes that contained STAT1 and not STAT3. Chronic treatment with LIF resulted in decreased protein levels of sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FAS), but had no effect on the expression of other adipocyte marker proteins or on TAG levels in mature 3T3-L1 adipocytes. LIF had a small effect on insulin-stimulated glucose uptake in 3T3-L1 adipocytes, but did not cause insulin resistance following chronic treatment. These findings indicate that LIF has similar and distinct effects in comparison with the effects of other gp130 cytokines on cultured fat cells. In summary, our results support a role for LIF in the regulation of proteins involved in lipid synthesis and in the modulation of signal transduction pathways in 3T3-L1 adipocytes.
Hogan
Jessica C
JC
Department of Biological Sciences, 202 Life Sciences Building, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Stephens
Jacqueline M
JM
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D051780:Sterol Regulatory Element Binding Protein 1; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C497388:Srebf1 protein, mouse; C494080:Stat1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D005947:Glucose