{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320725536000.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/diabetes.51.5.1319"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/51/5/1319/659060/db0502001319.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/51/5/1319/659060/db0502001319.pdf"}},{"identifier":{"@type":"NAID","@value":"30026274744"}}],"dc:title":[{"@value":"Tumor Necrosis Factor-α Suppresses Adipocyte-Specific Genes and Activates Expression of Preadipocyte Genes in 3T3-L1 Adipocytes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Tumor necrosis factor-α (TNF-α) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-α induces insulin resistance is not understood. By using 3T3-L1 adipocytes and oligonucleotide microarrays, we identified 142 known genes reproducibly upregulated by at least threefold after 4 h and/or 24 h of TNF-α treatment, and 78 known genes downregulated by at least twofold after 24 h of TNF-α incubation. TNF-α-induced genes include transcription factors implicated in preadipocyte gene expression or NF-κB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules. Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/enhancer binding protein-α, receptor retinoid X receptor-α, and peroxisome profilerator-activated receptor γ were significantly downregulated by TNF-α treatment. Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-α resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT). Nuclear factor-κB (NF-κB) was activated within 15 min of TNF-α addition. 3T3-L1 adipocytes expressing IκBα-DN, a nondegradable NF-κB inhibitor, exhibited normal morphology, global gene expression, and insulin responses. However, absence of NF-κB activation abolished suppression of &gt;98% of the genes normally suppressed by TNF-α and induction of 60–70% of the genes normally induced by TNF-α. Moreover, extensive cell death occurred in IκBα-DN-expressing adipocytes after 2 h of TNF-α treatment. Thus the changes in adipocyte gene expression induced by TNF-α could lead to insulin resistance. Further, NF-κB is an obligatory mediator of most of these TNF-α responses.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670320725536000","@type":"Researcher","foaf:name":[{"@value":"Hong Ruan"}],"jpcoar:affiliationName":[{"@value":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320725536001","@type":"Researcher","foaf:name":[{"@value":"Nir Hacohen"}],"jpcoar:affiliationName":[{"@value":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320725536003","@type":"Researcher","foaf:name":[{"@value":"Todd R. Golub"}],"jpcoar:affiliationName":[{"@value":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts"},{"@value":"Dana-Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320725536002","@type":"Researcher","foaf:name":[{"@value":"Luk Van Parijs"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts"},{"@value":"Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320725536004","@type":"Researcher","foaf:name":[{"@value":"Harvey F. Lodish"}],"jpcoar:affiliationName":[{"@value":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts"},{"@value":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"2002-05-01","prism:volume":"51","prism:number":"5","prism:startingPage":"1319","prism:endingPage":"1336"},"reviewed":"false","url":[{"@id":"https://journals.org/diabetes/diabetes/article-pdf/51/5/1319/659060/db0502001319.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/51/5/1319/659060/db0502001319.pdf"}],"createdAt":"2007-03-06","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050022708924660736","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Deletion of Hypoxia-Inducible Factor-1α in Adipocytes Enhances Glucagon-Like Peptide-1 Secretion and Reduces Adipose Tissue Inflammation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283689596050176","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Quercetin suppresses immune cell accumulation 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