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Horm Metab Res 2010; 42(10): 703-709
DOI: 10.1055/s-0030-1261872
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Insulin Resistance and Increased Lipolysis in Bone Marrow Derived Adipocytes Stimulated with Agonists of Toll-like Receptors

M. Franchini1 , E. Monnais2 , D. Seboek3 , T. Radimerski3 , E. Zini2 , K. Kaufmann2 , T. Lutz4 , C. Reusch2 , M. Ackermann1 , B. Muller3 , P. Linscheid2 , 3
  • 1Institute of Virology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
  • 2Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
  • 3Department of Research, University Hospital, Basel, Switzerland
  • 4Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland
Further Information

Publication History

received 21.12.2009

accepted 02.06.2010

Publication Date:
05 July 2010 (online)

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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-1β, IL-6, TNFα, 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.

Key words

inflammation - interleukin-6 - poly (I:C) - LPS - type 2 diabetes - obesity - insulin resistance

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Correspondence

M. Franchini

Institute of Virology

Vetsuisse faculty

University of Zurich

Winterthurerstraße 266a

8057 Zurich

Phone: +41/44/635 8717

Fax: +41/44/635 8911

Email: marco.franchini@vetvir.uzh.ch

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