Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Animals; *Diet, High-Fat; Energy Metabolism; Feedback, Physiological; Gene Expression Regulation; Iodide Peroxidase; MAP Kinase Signaling System; Mice; Obesity; Pituitary Gland, Anterior; Thyroid Hormones
Biochemistry | Cellular and Molecular Physiology | Endocrinology | Molecular Biology | Molecular Genetics
The cJun N-terminal kinase (JNK) signaling pathway is a key mediator of metabolic stress responses caused by consuming a high-fat diet, including the development of obesity. To test the role of JNK, we examined diet-induced obesity in mice with targeted ablation of Jnk genes in the anterior pituitary gland. These mice exhibited an increase in the pituitary expression of thyroid-stimulating hormone (TSH), an increase in the blood concentration of thyroid hormone (T4), increased energy expenditure, and markedly reduced obesity compared with control mice. The increased amount of pituitary TSH was caused by reduced expression of type 2 iodothyronine deiodinase (Dio2), a gene that is required for T4-mediated negative feedback regulation of TSH expression. These data establish a molecular mechanism that accounts for the regulation of energy expenditure and the development of obesity by the JNK signaling pathway.
DIO2, JNK, obesity, pituitary gland, thyroid hormone
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This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
DOI of Published Version
Vernia S, Cavanagh-Kyros J, Barrett T, Jung DY, Kim JK, Davis RJ. Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway. Genes Dev. 2013 Nov 1;27(21):2345-55. doi: 10.1101/gad.223800.113. Link to article on publisher's site
Genes and development
Vernia, Santiago; Cavanagh-Kyros, Julie; Barrett, Tamera; Jung, Dae Young; Kim, Jason K.; and Davis, Roger J., "Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway" (2013). Program in Molecular Medicine Publications and Presentations. 11.