title: Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity.
abstract: Signal transducers and activators of transcription (STATs) are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5), the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF.
authors.affiliation: Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Heike
authors.initials: H
authors.lastname: Muenzberg
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Reed
authors.forename: Darlene
authors.initials: D
authors.lastname: Berryman
authors.forename: Eneida C
authors.initials: EC
authors.lastname: Villanueva
authors.forename: Gwendolyn W
authors.initials: GW
authors.lastname: Louis
authors.forename: Gina M
authors.initials: GM
authors.lastname: Leinninger
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertuzzi
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: Gertraud W
authors.initials: GW
authors.lastname: Robinson
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology; D004734:Energy Metabolism; D005260:Female; D006706:Homeostasis; D007031:Hypothalamus / Q000166:cytology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000209:etiology*; D010902:Pituitary Gland / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse