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A central role for JNK in obesity and insulin resistance

Nature volume 420, pages 333–336 (2002)Cite this article

An Author Correction to this article was published on 16 June 2023

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Abstract

Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood1. The c-Jun amino-terminal kinases (JNKs) can interfere with insulin action in cultured cells2 and are activated by inflammatory cytokines and free fatty acids, molecules that have been implicated in the development of type 2 diabetes3,4. Here we show that JNK activity is abnormally elevated in obesity. Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity. Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics.

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Figure 1: Total JNK activity and development of diet-induced obesity.
Figure 2: Adipose tissue morphology and adiposity in Jnk1 -/- mice and wild-type controls.
Figure 3: Metabolic effects of JNK1-deficiency.
Figure 4: JNK activity and insulin signalling in JNK1-deficient mice.

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Acknowledgements

This work is in part supported by grants from the National Institutes of Health (M.K. and G.S.H.) and the Pew Foundation (G.S.H.).

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Author notes

  1. Jiro Hirosumi, Gürol Tuncman, Lufen Chang and Michael Karin: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Massachusetts, 02115, Boston, USA

    Jiro Hirosumi, Gürol Tuncman, Cem Z. Görgün, K. Teoman Uysal, Kazuhisa Maeda & Gökhan S. Hotamisligil

  2. Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California , School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093, San Diego, USA

    Lufen Chang & Michael Karin

Authors
  1. Jiro Hirosumi
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  8. Gökhan S. Hotamisligil
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Correspondence to Gökhan S. Hotamisligil.

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Hirosumi, J., Tuncman, G., Chang, L. et al. A central role for JNK in obesity and insulin resistance. Nature 420, 333–336 (2002). https://doi.org/10.1038/nature01137

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