title: Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway.
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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Santiago
authors.initials: S
authors.lastname: Vernia
authors.forename: Julie
authors.initials: J
authors.lastname: Cavanagh-Kyros
authors.forename: Tamera
authors.initials: T
authors.lastname: Barrett
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D007453:Iodide Peroxidase / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II
keywords: DIO2; JNK; obesity; pituitary gland; thyroid hormone