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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#_3 http://www.w3.org/ns/prov#value OBJECTIVE: To examine the effect of a high-fat diet on gene expression in adipose tissues and to determine induction kinetics of adipose monocyte chemoattractant protein-1 and -3 (MCP-1 and MCP-3) in diet-induced obesity (DIO) and the effect of a lack of MCP-1 signaling on DIO susceptibility and macrophage recruitment into adipose tissue. RESEARCH METHODS AND PROCEDURES: Obese and lean adipose tissues were profiled for expression changes. The time-course of MCP-1 and MCP-3 expression was examined by reverse transcriptase-polymerase chain reaction. Plasma MCP-1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Chemokine receptor-2 (CCR2) knockout mice were placed on the high-fat diet to determine DIO susceptibility. Macrophage infiltration in adipose tissue was examined by immunohistochemistry with F4/80 antibody. RESULTS: DIO elevated adipose expression of many inflammatory genes, including MCP-1 and MCP-3. Adipose MCP-1 and MCP-3 mRNA levels increased within 7 days of starting a high-fat diet, with elevation of plasma MCP-1 detected after 4 weeks on the diet. The induction of MCP-1 and MCP-3 expression preceded that of tumor necrosis factor-alpha. The elevated plasma MCP-1 concentration in obese mice was partially reversed by treatment with AM251. No change in DIO susceptibility and macrophage accumulation in adipose tissue were observed in CCR2 knockout mice, which lack the MCP-1 receptor CCR2. DISCUSSION: A high-fat diet elevated adipose expression of inflammatory genes, including early induction of MCP-1 and MCP-3, supporting the view that obese adipose tissues contribute to systemic inflammation. However, despite increased MCP-1 in obesity, disruption of MCP-1 signaling did not confer resistance to DIO in mice or reduce adipose tissue macrophage infiltration. http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/16129712 http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/16129712 http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#_3 http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58#pubinfo http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58 http://purl.org/dc/terms/created 2014-07-03T14:30:37.844+02:00 http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAYFG1bYzD5aP3r_YLdaIEWQFGnlZzzR0ZmRP8KftXs58 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234