title: Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice.
abstract: The proposition that white adipose tissue is involved in the inflammatory response and metabolic dysregulation of endotoxaemia has been examined. Mice were injected with lipopolysaccharide (LPS; 25 mg/kg) and epididymal, perirenal and subcutaneous adipose tissue removed 4 or 24 h later. The expression of genes encoding key inflammation-related adipokines was measured by real-time polymerase chain reaction. At 24 h after the administration of LPS, there was no change in leptin mRNA level, and adiponectin mRNA fell. However, major increases in TNFalpha, MCP-1 (up to 40-fold) and IL-6 (up to 250-fold) mRNA levels were evident; a substantial elevation in these mRNAs occurred by 4 h, and adipose tissue IL-6 protein also increased (three- to eightfold). At 24 h, the responses in the subcutaneous depot were much lower than in epididymal and perirenal adipose tissue, but at 4 h, the subcutaneous tissue showed major increases in IL-6, MCP-1 and TNFalpha gene expression. In contrast to the inflammatory adipokines, the mRNA level of two macrophage markers, F4/80 and MAC-1, was unaltered in adipose tissue during endotoxaemia. Expression of the hypoxia-sensitive transcription factor, HIF-1alpha, gene was increased at both 4 and 24 h, and HIF-1alpha protein was elevated at 4 h, suggesting that the tissue was hypoxic. It is concluded that white adipose tissue may play an important role in the production of inflammatory mediators in endotoxaemia.
authors.affiliation: Critical Care Research Unit, School of Clinical Sciences, University of Liverpool, University Clinical Departments, Duncan Building, Liverpool, L69 3GA, UK. mleuwer@liverpool.ac.uk
authors.forename: Martin
authors.initials: M
authors.lastname: Leuwer
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Welters
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
authors.forename: Andrew
authors.initials: A
authors.lastname: Rushton
authors.forename: Hongguang
authors.initials: H
authors.lastname: Bao
authors.forename: Leif
authors.initials: L
authors.lastname: Hunter
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000276:immunology; D052436:Adipose Tissue, White / Q000276:immunology*; D000818:Animals; D019446:Endotoxemia / Q000276:immunology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D054392:Adipokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides