title: GPR17 gene disruption does not alter food intake or glucose homeostasis in mice.
abstract: G protein-coupled receptor 17 (GPR17) was recently reported to be a Foxo1 target in agouti-related peptide (AGRP) neurons. Intracerebroventricular injection of GPR17 agonists induced food intake, whereas administration of an antagonist to the receptor reduced feeding. These data lead to the conclusion that pharmacological modulation of GPR17 has therapeutic potential to treat obesity. Here we report that mice deficient in Gpr17 (Gpr17(-/-)) have similar food intake and body weight compared with their wild-type littermates. Gpr17(-/-) mice have normal hypothalamic Agrp mRNA expression, AGRP plasma levels, and metabolic rate. GPR17 deficiency in mice did not affect glucose homeostasis or prevent fat-induced insulin resistance. These data do not support a role for GPR17 in the control of food intake, body weight, or glycemic control.
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and Jason.Mastaitis@regeneron.com george@regeneron.com.
authors.forename: Jason
authors.initials: J
authors.lastname: Mastaitis
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Soo
authors.initials: S
authors.lastname: Min
authors.affiliation: Sanofi Diabetes Research and Translational Medicine, D-65926 Frankfurt am Main, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Elvert
authors.affiliation: Sanofi Diabetes Research and Translational Medicine, D-65926 Frankfurt am Main, Germany.
authors.forename: Aimo
authors.initials: A
authors.lastname: Kannt
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Francisca
authors.initials: F
authors.lastname: Ochoa
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gale
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and Jason.Mastaitis@regeneron.com george@regeneron.com.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
authors.forename: Jesper
authors.initials: J
authors.lastname: Gromada
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001823:Body Composition / Q000187:drug effects; D004435:Eating / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017423:Sequence Analysis, RNA; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; C534979:GPR17 protein, mouse; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D005947:Glucose
keywords: AGRP; GPR17; body weight; diabetes; food intake