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Horm Metab Res 2009; 41(7): 523-530
DOI: 10.1055/s-0029-1202852
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

The c-Jun N-Terminal Kinase Mediates the Induction of Oxidative Stress and Insulin Resistance by Palmitate and Toll-like Receptor 2 and 4 Ligands in 3T3-L1 Adipocytes

J. E. Davis 1 , 3 , N. K. Gabler 2 , J. Walker-Daniels 1 , M. E. Spurlock 1 , 2
  • 1Iowa State University, Food Science Human Nutrition, Ames, IA, USA
  • 2Iowa State University, Animal Science, Ames, IA, USA
  • 3Southern Illinois University, Animal Science, Food and Nutrition, Carbondale, IL, USA
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Publication History

received 04.11.2008

accepted 12.01.2009

Publication Date:
10 March 2009 (online)

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Abstract

Saturated fatty acids (SFAs) are known to induce inflammation and insulin resistance in adipocytes through toll-like receptor-4 (Tlr4) signaling, but the mechanisms are not well delineated. Furthermore, the potential roles of Tlr2 and the c-Jun N-terminal kinase (JNK) in inflammation in adipocytes have not been investigated. We demonstrated that palmitate, lipopolysaccharide (LPS), and the toll-like receptor-2 (Tlr2) agonist, zymosan A (ZymA), induced insulin resistance in a time- and dose-dependent manner in 3T3-L1 adipocytes. Corresponding with the reduction of insulin sensitivity was an increased expression of IL-6, as well as activation of the proinflammatory transcription factors, nuclear factor kappa B, and activator protein-1. Reactive oxygen species (ROS) accumulation was also observed in palmitate and Tlr agonist treated adipocytes. The JNK inhibitor, SP600125, attenuated insulin resistance mediated by SFA and Tlr agonists, which corresponded with a diminished proinflammatory response and reduced ROS accumulation. Collectively, these results demonstrated Tlr2 involvement in adipocyte inflammation and therefore implicated the receptor as a potential target for SFA. Moreover, activation of JNK also appeared to be essential to Tlr2-, as well as Tlr4-induced insulin resistance and oxidative stress.

Key words

adipose tissue - obesity - cytokines - chemokines

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Correspondence

M. E. Spurlock

Department of Food Science and Human Nutrition

Iowa State University

50011 Ames

USA

Phone: +1/515/294 50 38

Fax: +1/515/294 61 93

Email: mspurloc@iastate.edu