Signaling pathways utilized by tumor necrosis factor receptor 1 in adipocytes to suppress differentiation.
Tumor necrosis factor-alpha (TNFalpha) has profound effects on cultured adipocytes, one of which is the inhibition of terminal differentiation. Previous studies in TNF receptor (TNFR)-deficient preadipocytes have demonstrated that the anti-adipogenic effect of both secreted and transmembrane TNFalpha is mediated solely by TNFR1. In this study, we performed a structure-function analysis of the intracellular domains of TNFR1 and investigated the signaling pathway(s) involved in TNFR1-mediated inhibition of adipocyte differentiation. Our results show that repression of adipogenesis required the juxtamembrane and death domains and was independent of the pathways involving nuclear factor kappaB and neutral sphingomyelinase.
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Harvard School of Public Health, Division of Biological Sciences and Department of Nutrition, 665 Huntington Ave., Boston, MA 02115, USA.
Hotamisligil
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D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D017930:Genes, Reporter / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D015415:Biomarkers; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha