title: Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin.
abstract: The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. Dissipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916±952 pg/mL vs. 23474±1507 pg/mL, P<.01) while no change was observed for insulin, IGF-1 or leptin. GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of its down-regulation.
authors.affiliation: Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dubins
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: Victor
authors.initials: V
authors.lastname: Zhukov
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez-Gonzalez
authors.forename: Gianluca
authors.initials: G
authors.lastname: Moroncini
authors.forename: Santos
authors.initials: S
authors.lastname: Carvajal-Gonzalez
authors.forename: John R
authors.initials: JR
authors.lastname: Hadcock
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001833:Body Temperature Regulation; D015536:Down-Regulation; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011301:Preoptic Area / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000502:physiology*; D015430:Weight Gain
chemical_list: D052242:Adiponectin; C501984:Gpr83 protein, mouse; D020738:Leptin; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D007334:Insulin-Like Growth Factor I