Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

Bengt F Belgardt; Jan Mauer; F Thomas Wunderlich; Marianne B Ernst; Martin Pal; Gabriele Spohn; Hella S Broenneke; Susanne Brodesser; Brigitte Hampel; Astrid C Schauss; Jens C Bruening

Journal article

Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

Bengt F Belgardt, Jan Mauer, F Thomas Wunderlich, Marianne B Ernst, Martin Pal, Gabriele Spohn, Hella S Broenneke, Susanne Brodesser, Brigitte Hampel, Astrid C Schauss, Jens C Bruening

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2010

DOI: 10.1073/pnas.1001796107

Abstract

c-Jun N-terminal kinase (JNK) 1-dependent signaling plays a crucial role in the development of obesity-associated insulin resistance. Here we demonstrate that JNK activation not only occurs in peripheral tissues, but also in the hypothalamus and pituitary of obese mice. To resolve the importance of JNK1 signaling in the hypothalamic/pituitary circuitry, we have generated mice with a conditional inactivation of JNK1 in nestin-expressing cells (JNK1(DeltaNES) mice). JNK1(DeltaNES) mice exhibit improved insulin sensitivity both in the CNS and in peripheral tissues, improved glucose metabolism, as well as protection from hepatic steatosis and adipose tissue dysfunction upon high-fat feeding. Mor..

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University of Melbourne Researchers

Martin Pal Author Medical Biology (W.E.H.I.)

Grants

Awarded by European Union

Awarded by Fritz Thyssen Stiftung

Awarded by German Research Foundation

Awarded by European Community

Funding Acknowledgements

We thank G. Schmall and Tanja Rayle for excellent secretarial assistance and Pia Scholl, Sonja Becker, and Jens Alber for outstanding technical assistance. This work was supported by grants from the Center of Molecular Medicine Cologne (TV2) and the European Union (LSHM-CT-2003-503041) to J.C.B., the Fritz Thyssen Stiftung (Az. 10.04.1.153/Az. 10.06.2.175) to J.C.B., the European Foundation for the Study of Diabetes/Lilly European Diabetes Research Programme to J.C.B., and the German Research Foundation (Deutsche Forschungsgemeinschaft) (Br. 1492/7-1) to J. C.B., and research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013), acronym "TOBI," under grant agreement no. 201608 (to J.C.B.).