Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism
- 15 March 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (13), 6028-6033
- https://doi.org/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(Delta NES) mice). JNK1(Delta NES) 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(Delta NES) 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.Keywords
This publication has 41 references indexed in Scilit:
- Hormone and glucose signalling in POMC and AgRP neuronsThe Journal of Physiology, 2009
- Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat dietAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin ResistanceCell Metabolism, 2009
- A Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin ResistanceScience, 2008
- Inflammation and endoplasmic reticulum stress in obesity and diabetesInternational Journal of Obesity, 2008
- Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and ObesityCell, 2008
- Growth Hormone, Insulin-Like Growth Factors, and the SkeletonEndocrine Reviews, 2008
- Genetic approaches identify adult pituitary stem cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- Inflammation and metabolic disordersNature, 2006
- Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restrictionProceedings of the National Academy of Sciences of the United States of America, 2006