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Science 5 December 2008:
Vol. 322. no. 5907, pp. 1539 - 1543
DOI: 10.1126/science.1160794
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Reports

A Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin Resistance

Guadalupe Sabio,1,2 Madhumita Das,2 Alfonso Mora,2 Zhiyou Zhang,3 John Y. Jun,3,4 Hwi Jin Ko,3 Tamera Barrett,2 Jason K. Kim,3 Roger J. Davis1,2*

A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene was ablated selectively in adipose tissue. JNK1 deficiency in adipose tissue suppressed high-fat diet–induced insulin resistance in the liver. JNK1-dependent secretion of the inflammatory cytokine interleukin-6 by adipose tissue caused increased expression of liver SOCS3, a protein that induces hepatic insulin resistance. Thus, JNK1 activation in adipose tissue can cause insulin resistance in the liver.

1 Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3 Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
4 Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

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

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Interleukin-10 Prevents Diet-Induced Insulin Resistance by Attenuating Macrophage and Cytokine Response in Skeletal Muscle.
E.-G. Hong, H. J. Ko, Y.-R. Cho, H.-J. Kim, Z. Ma, T. Y. Yu, R. H. Friedline, E. Kurt-Jones, R. Finberg, M. A. Fischer, et al. (2009)
Diabetes 58, 2525-2535
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MCP-1 (Monocyte Chemotactic Protein-1)-induced Protein, a Recently Identified Zinc Finger Protein, Induces Adipogenesis in 3T3-L1 Pre-adipocytes without Peroxisome Proliferator-activated Receptor {gamma}.
C. W. Younce, A. Azfer, and P. E. Kolattukudy (2009)
J. Biol. Chem. 284, 27620-27628
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Activated Ask1-MKK4-p38MAPK/JNK Stress Signaling Pathway in Human Omental Fat Tissue May Link Macrophage Infiltration to Whole-Body Insulin Sensitivity.
M. Bluher, N. Bashan, I. Shai, I. Harman-Boehm, T. Tarnovscki, E. Avinaoch, M. Stumvoll, A. Dietrich, N. Kloting, and A. Rudich (2009)
J. Clin. Endocrinol. Metab. 94, 2507-2515
   Abstract »    Full Text »    PDF »
A Dual Role of CD4+ T Cells in Adipose Tissue?.
C. M. Matter and M. A. S. Stein (2009)
Circ. Res. 104, 928-930
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