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Science 339 (6116): 218-222

Copyright © 2013 by the American Association for the Advancement of Science

JNK Expression by Macrophages Promotes Obesity-Induced Insulin Resistance and Inflammation

Myoung Sook Han,1,2 Dae Young Jung,2 Caroline Morel,1,2 Saquib A. Lakhani,3,* Jason K. Kim,2,4 Richard A. Flavell,3 Roger J. Davis1,2,{dagger}

Abstract: The cJun NH2-terminal kinase (JNK) signaling pathway contributes to inflammation and plays a key role in the metabolic response to obesity, including insulin resistance. Macrophages are implicated in this process. To test the role of JNK, we established mice with selective JNK deficiency in macrophages. We report that feeding a high-fat diet to control and JNK-deficient mice caused similar obesity, but only mice with JNK-deficient macrophages remained insulin-sensitive. The protection of mice with macrophage-specific JNK deficiency against insulin resistance was associated with reduced tissue infiltration by macrophages. Immunophenotyping demonstrated that JNK was required for pro-inflammatory macrophage polarization. These studies demonstrate that JNK in macrophages is required for the establishment of obesity-induced insulin resistance and inflammation.

1 Howard Hughes Medical Institute, Worcester, MA 01605, USA.
2 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3 Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CN 06520, USA.
4 Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, MA 01605, USA.

* Present address: Department of Pediatrics, Sanford University School of Medicine, Sioux Falls, SD 57117, USA.

{dagger} To whom correspondence should be addressed. E-mail: roger.davis{at}umassmed.edu


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