Journal
INNATE IMMUNITY
Volume 18, Issue 1, Pages 25-34Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425910386632
Keywords
Human adipocytes; inflammation; interleukin-6; interleukin-8; lipolysis; lipopolysaccharides
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Funding
- University of Basel (Forschungsfonds-Forderung fur Nachwuchsforschende der Universitat Basel)
- Stiftung der Diabetes-Gesellschaft Region Basel
- Novartis Stiftung fur Medizinisch-Biologische Forschung [PP00P3_123346/1]
- Sanofi-Aventis
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High fat diet-induced endotoxaemia triggers low-grade inflammation and lipid release from adipose tissue. This study aims to unravel the cellular mechanisms leading to the lipopolysaccharide (LPS) effects in human adipocytes. Subcutaneous pre-adipocytes surgically isolated from patients were differentiated into mature adipocytes in vitro. Lipolysis was assessed by measurement of glycerol release and mRNA expression of pro-inflammatory cytokines were evaluated by real-time PCR. Treatment with LPS for 24 h induced a dose-dependent increase in interleukin (IL)-6 and IL-8 mRNA expression. At 1 mu g/ml LPS, IL-6 and IL-8 were induced to 19.5 +/- 1.8-fold and 662.7 +/- 91.5-fold (P < 0.01 vs basal), respectively. From 100 mu g/ml to 1 mg/ml, LPS-induced lipolysis increased to a plateau of 3.1-fold above basal level (P < 0.001 vs basal). Co-treatment with inhibitors of inhibitory kappa B kinase kinase beta (IKK beta) or NF-kappa B inhibited LPS-induced glycerol release. Co-treatment with the protein kinase A (PKA) inhibitor H-89, the lipase inhibitor orlistat or the hormone-sensitive lipase (HSL) inhibitor CAY10499 abolished the lipolytic effects of LPS. Co-treatment with the MAPK inhibitor, U0126 also reduced LPS-induced glycerol release. Inhibition of lipolysis by orlistat or CAY10499 reduced LPS-induced IL-6 and IL-8 mRNA expression. Induction of lipolysis by the synthetic catecholamine isoproterenol or the phosphodiesterase type III inhibitor milrinone did not alter basal IL-6 and IL-8 mRNA expression after 24 treatments whereas these compounds enhanced LPS-induced IL-6 and IL-8 mRNA expression. Both the inflammatory IKK beta/NF-kappa B pathway and the lipolytic PKA/HSL pathways mediate LPS-induced lipolysis. In turn, LPS-induced lipolysis reinforces the expression of pro-inflammatory cytokines and, thereby, triggers its own lipolytic activity.
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