title: mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts.
abstract: G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden; Faculty of Pharmacy, University of Tasmania (UTAS), 7001 Hobart, Australia. Electronic address: vanni.caruso@neuro.uu.se.
authors.forename: Vanni
authors.initials: V
authors.lastname: Caruso
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Smitha
authors.initials: S
authors.lastname: Sreedharan
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden; Departamento de Farmacología, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, Universidad Nacional de Córdoba, 5016 Córdoba, Argentina.
authors.forename: Valeria P
authors.initials: VP
authors.lastname: Carlini
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Josefin A
authors.initials: JA
authors.lastname: Jacobsson
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Haitina
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Joanna
authors.initials: J
authors.lastname: Hammer
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Stephansson
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Crona
authors.affiliation: Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Sommer
authors.affiliation: Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.affiliation: Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department for Clinical Science, Intervention and Technology, Karolinska Institute, Division of Pediatrics, National Childhood Obesity Centre, Stockholm, Sweden.
authors.forename: Claude
authors.initials: C
authors.lastname: Marcus
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.affiliation: Departamento de Farmacología, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, Universidad Nacional de Córdoba, 5016 Córdoba, Argentina.
authors.forename: Susana R
authors.initials: SR
authors.lastname: de Barioglio
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University BMC, Uppsala SE 75124, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000378:metabolism; D002648:Child; D004435:Eating; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D013548:Sweden; D014018:Tissue Distribution
chemical_list: C000609486:GPR162 protein, rat; C569435:Gpr162 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D005947:Glucose
keywords: Food intake; GPCRs; GPR162; Glucose homeostasis; Obesity