Role of the hypothalamic–pituitary–thyroid axis in metabolic regulation by JNK1
- Guadalupe Sabio1,2,5,
- Julie Cavanagh-Kyros1,2,
- Tamera Barrett1,2,
- Dae Young Jung2,3,
- Hwi Jin Ko2,3,
- Helena Ong2,
- Caroline Morel1,2,
- Alfonso Mora2,
- Judith Reilly2,
- Jason K. Kim2,3,4 and
- Roger J. Davis1,2,6
- 1Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 3Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA;
- 4Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Abstract
The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic–pituitary–thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic–pituitary–thyroid axis represents an important target of metabolic signaling by JNK1.
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Footnotes
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↵6 Corresponding author.
E-MAIL roger.davis{at}umassmed.edu; FAX (508) 856-3210.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1878510.
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Supplemental material is available at http://www.genesdev.org.
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- Received October 27, 2007.
- Accepted December 4, 2009.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
