Endothelin-1 inhibits adipogenesis: role of phosphorylation of Akt and ERK1/2.
In adipogenesis, growth factors play a crucial role. Using serum depleted condition, we studied the causal role of endothelin-1 (ET-1) and epidermal growth factor (EGF), separately or together, in adipocyte differentiation of 3T3-L1 cells. ET-1 stimulation caused an anti-adipogenic response and this effect was potentiated upon treatment with EGF. Co-treatment with EGF and ET-1 blocked the expression of C/EBPalpha and PPARgamma, the adipogenic markers. The inhibition of adipogenesis was preceded by a biphasic (early and late) attenuation of Akt phosphorylation. We suggest that treatment with ET-1 and EGF together induce a more potent anti-adipogenic response, involving increased Erk1/2 phosphorylation and biphasic attenuation of Akt phosphorylation.
Bhattacharya
Indranil
I
Department of Molecular Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Ullrich
Axel
A
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism
D015415:Biomarkers; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3