title: Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice.
abstract: Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murine Gpr1 mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) and Cmklr1, Gpr1 expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygous Gpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lacking Gpr1 exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects of Gpr1 deficiency on adiposity, energy balance, and glucose homeostasis in vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.
authors.affiliation: Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Rourke
authors.affiliation: Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Muruganandan
authors.affiliation: Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Dranse
authors.affiliation: Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: McMullen
authors.affiliation: Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 csinal@dal.ca.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D018925:Chemokines; D002630:Chemotactic Factors / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000502:physiology*
chemical_list: C102741:CMKLR1 protein, human; D018925:Chemokines; D002630:Chemotactic Factors; C000591279:GPR1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse; D005947:Glucose
keywords: CMKLR1; GPR1; chemerin; glucose homeostasis; obesity