Hypothalamic and Pituitary C-Jun N-terminal Kinase 1 Signaling Coordinately Regulates Glucose Metabolism

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Mar 17

PMID 20231445

Citations 89

Authors

Bengt F Belgardt

Jan Mauer

F Thomas Wunderlich

Marianne B Ernst

Martin Pal

Gabriele Spohn

Hella S Bronneke

Susanne Brodesser

Brigitte Hampel

Astrid C Schauss

Jens C Bruning

Affiliations

Soon will be listed here.

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. Moreover, JNK1(DeltaNES) mice also show reduced somatic growth in the presence of reduced circulating growth hormone (GH) and insulin-like growth factor 1 (IGF1) concentrations, as well as increased thyroid axis activity. Collectively, these experiments reveal an unexpected, critical role for hypothalamic/pituitary JNK1 signaling in the coordination of metabolic/endocrine homeostasis.

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