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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-41244

Franchini, M; Monnais, E; Seboek, D; Radimerski, T; Zini, E; Kaufmann, K; Lutz, T; Reusch, C; Ackermann, M; Muller, B; Linscheid, P (2010). Insulin resistance and increased lipolysis in bone marrow derived adipocytes stimulated with agonists of Toll-like receptors. Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et métabolisme, 42(10):703-709.

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Abstract

Our objectives were to identify Toll-like receptors (TLRs) in human bone marrow derived adipocytes, to test specific TLR agonists for their ability to induce a proinflammatory response, and to investigate possible metabolic effects after TLR activation, in particular, those associated with insulin resistance and lipolysis. Mesenchymal stem cells were isolated from human bone marrow and differentiated into adipocytes. Total RNA before or after stimulation with agonists specific for TLR was extracted for analysis of expression of TLRs proinflammatory signals and molecules involved in glucose metabolism (IRS-1 and GLUT4). Furthermore, cytokine protein expression was measured from cell lysates. Finally, insulin induced glucose uptake and lipolysis were measured. Human bone marrow-derived adipocytes express TLR1-10. They react to stimulation with specific ligands with expression of inflammatory markers (IL-1beta, IL-6, TNFalpha, IL-8, MCP-1) at the RNA and protein levels. IRS-1 and GLUT4 expression was downregulated after stimulation with the TLR4 and TLR3 specific ligands LPS and poly (I:C), respectively. Insulin-induced glucose uptake was decreased and lipolysis increased. We conclude that adipocytes express TLR 1-10 and react to agonists specific for TLR 1-6. As a consequence proinflammatory cytokine are induced, in particular, IL-6, IL-8, and MCP-1. Since stimulation is followed by decreased insulin-induced glucose uptake and increased lipolysis we conclude that TLRs may be important linking molecules in the generation of insulin resistance in fat tissue.

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals > Clinic for Small Animal Internal Medicine
05 Vetsuisse Faculty > Institute of Virology
DDC:570 Life sciences; biology
630 Agriculture
Date:2010
Deposited On:02 Feb 2011 14:54
Last Modified:27 Nov 2013 19:47
Publisher:Thieme
ISSN:0018-5043
Publisher DOI:10.1055/s-0030-1261872
PubMed ID:20603780
Citations:Web of Science®. Times Cited: 6
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Scopus®. Citation Count: 8

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