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Sci. Signal., 9 December 2008
Vol. 1, Issue 49, p. ec420
[DOI: 10.1126/scisignal.149ec420]


Medicine Toward Normalizing Metabolic Regulation

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

Mice fed a diet high in fat develop resistance to the action of the hormone insulin, much as do humans suffering from the disease known as metabolic syndrome. Sabio et al. (see the Perspective by Ogawa and Kasuga) present evidence that the mitogen-activated protein kinase JNK1 is a key player in this process. The authors created conditional knockout mice in which JNK was no longer expressed in adipose tissue (fat). When fed a diet high in fat, these animals still showed increased concentrations of glucose and insulin in the blood, but measures of insulin responsiveness in the liver showed that the knockout animals retained a stronger response than did wild-type mice. Adipose tissue appeared to communicate with the liver through release of the cytokine interleukin 6 (IL-6). The knockout animals had less IL-6 in the blood after fasting than did control animals, and restoration of IL-6 in the knockouts reduced liver responsiveness to insulin. Thus, JNK1 represents a potential target for therapies aimed at improving metabolic control in diseases in which normal regulation is disrupted.

G. Sabio, M. Das, A. Mora, Z. Zhang, J. Y. Jun, H. J. Ko, T. Barrett, J. K. Kim, R. J. Davis, A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science 322, 1539–1543 (2008). [Abstract] [Full Text]

W. Ogawa, M. Kasuga, Fat stress and liver resistance. Science 322, 1483–1484 (2008). [Summary] [Full Text]

Citation: L. B. Ray, Toward Normalizing Metabolic Regulation. Sci. Signal. 1, ec420 (2008).

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