Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway.
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.
['Vernia|Santiago|S|', 'Cavanagh-Kyros|Julie|J|', 'Barrett|Tamera|T|', 'Jung|Dae Young|DY|', 'Kim|Jason K|JK|', 'Davis|Roger J|RJ|']
D000818:Animals D059305:Diet, High-Fat D004734:Energy Metabolism D025461:Feedback, Physiological D005786:Gene Expression Regulation D007453:Iodide Peroxidase D020935:MAP Kinase Signaling System D051379:Mice D009765:Obesity D010903:Pituitary Gland, Anterior D013963:Thyroid Hormones
obesity JNK DIO2 pituitary gland thyroid hormone