UMMS Affiliation
Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Publication Date
2013-11-01
Document Type
Article
Subjects
Animals; *Diet, High-Fat; Energy Metabolism; Feedback, Physiological; Gene Expression Regulation; Iodide Peroxidase; MAP Kinase Signaling System; Mice; Obesity; Pituitary Gland, Anterior; Thyroid Hormones
Disciplines
Biochemistry | Cellular and Molecular Physiology | Endocrinology | Molecular Biology | Molecular Genetics
Abstract
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.
Keywords
DIO2, JNK, obesity, pituitary gland, thyroid hormone
Rights and Permissions
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
10.1101/gad.223800.113
Source
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
Journal/Book/Conference Title
Genes and development
Related Resources
PubMed ID
24186979
Repository Citation
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.
https://escholarship.umassmed.edu/pmm_pp/11
Included in
Biochemistry Commons, Cellular and Molecular Physiology Commons, Endocrinology Commons, Molecular Biology Commons, Molecular Genetics Commons