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Both inflammatory and classical lipolytic pathways are involved in lipopolysaccharide-induced lipolysis in human adipocytes

Grisouard, Jean and Bouillet, Elisa and Timper, Katharina and Radimerski, Tanja and Dembinski, Kaethi and Frey, Daniel M. and Peterli, Ralph and Zulewski, Henryk and Keller, Ulrich and Muller, Beat and Christ-Crain, Mirjam. (2012) Both inflammatory and classical lipolytic pathways are involved in lipopolysaccharide-induced lipolysis in human adipocytes. Innate Immunity , 18 (1). pp. 25-34.

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Official URL: http://edoc.unibas.ch/dok/A6005899

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Abstract

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?µg/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?ng/ml to 1?µg/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?) or NF-?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?/NF-?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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Klinische Endokrinologie (Keller)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Metabolism (Keller/Müller)
UniBasel Contributors:Christ-Crain, Mirjam and Zulewski, Henryk and Keller, Ulrich O. and Müller, Beat
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Sage Publications
ISSN:0968-0519
e-ISSN:1743-2839
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Nov 2017 11:13
Deposited On:26 Apr 2013 06:58

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