Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling pathways.
Adipocytes play a key role in energy homeostasis and several cytokines have been shown to regulate adipogenesis. While the interleukin (IL)-6 family of cytokines was previously reported to be involved in adipogenesis, roles of this family in adipogenesis and their mechanisms of action are not fully understood. Here we show that among the IL-6 family, oncostatin M (OSM) most strongly inhibits adipogenesis of 3T3-L1 cells and mouse embryonic fibroblasts (MEFs). We also demonstrate that OSM inhibits adipogenesis through the Ras/extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT) 5 signaling pathways. In addition, OSM inhibits the early phase of the differentiation without affecting cell proliferation throughout adipogenesis including mitotic clonal expansion. CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPbeta, and peroxisome proliferator-activated receptor (PPAR) gamma are known to be required for adipogenesis. Expression of C/EBPalpha and PPARgamma was almost completely abrogated by OSM. In contrast, neither the mRNA nor protein level of C/EBPbeta was affected by OSM. Forced expression of C/EBPbeta induced differentiation in the presence of troglitazone, and OSM inhibited this C/EBPbeta-induced differentiation. Taken together, our results indicate that OSM inhibits the onset of terminal differentiation of adipocytes through the Ras/ERK and STAT5 signaling pathways by possibly regulating C/EBPbeta activity.
Miyaoka
Yuichiro
Y
Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Tanaka
Minoru
M
Naiki
Takahiro
T
Miyajima
Atsushi
A
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D053683:Oncostatin M / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D053683:Oncostatin M; D018631:ras Proteins