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Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 4, pp 731–741 | Cite as

Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice

  • Martin Leuwer
  • Ingeborg Welters
  • Gernot Marx
  • Andrew Rushton
  • Hongguang Bao
  • Leif Hunter
  • Paul Trayhurn
Integrative Physiology

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 TNFα, 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 TNFα 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-1α, gene was increased at both 4 and 24 h, and HIF-1α 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.

Keywords

Adipokines Adipose tissue Endotoxaemia IL-6 Inflammation Sepsis 

Notes

Acknowledgement

We gratefully acknowledge the receipt of funding from the Biotechnology and Biological Sciences Research Council (UK) to PT. The authors declare that they have no conflicts of interest with respect to this study. PT is a member of COST BM0602.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Martin Leuwer
    • 1
  • Ingeborg Welters
    • 1
  • Gernot Marx
    • 3
  • Andrew Rushton
    • 1
  • Hongguang Bao
    • 1
  • Leif Hunter
    • 2
  • Paul Trayhurn
    • 2
  1. 1.Critical Care Research Unit, School of Clinical SciencesUniversity of Liverpool, University Clinical DepartmentsLiverpoolUK
  2. 2.Obesity Biology Research Unit, School of Clinical SciencesUniversity of Liverpool, University Clinical DepartmentsLiverpoolUK
  3. 3.University Clinic for Anaesthesiology and Intensive Care, University of JenaJenaGermany

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