Logotyp: till Uppsala universitets webbplats

uu.sePublikationer från Uppsala universitet
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
GPR162 is expressed in the hypothalamus and is involved in food intake related behaviour
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
Departamento de Farmacología, Universidad Nacional de Córdoba, Argentina.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
Visa övriga samt affilieringar
2011 (Engelska)Artikel i tidskrift (Övrigt vetenskapligt) Submitted
Abstract [en]

The Rhodopsin family of G protein-coupled receptors (GPCRs) includes about 270 non-olfactory receptors and is the largest family of GPCRs. About sixty non-olfactory Rhodopsin GPCRs are still orphans without known ligands, and fairly little is known about their functions. In this study, we present molecular, neuroanatomical, genetic and behavioral data implicating a Rhodopsin family protein, GPR162, in the regulation of food intake-related behaviour and glucose homeostasis. The real-time PCR data show that GPR162 is predominantly expressed in the CNS. The in situ hybridization results confirmed significant expression of GPR162 in several hypothalamic sites, amygdala, substantia nigra and ventral tegmental area, among others regions. In line with the distribution of the GPR162 mRNA in the feeding circuitry, antisense oligo knockdown of GPR162 caused a significant reduction in food intake but no effect was observed towards reduction in body weight in rats. Our human genetics studies suggest that genetic variants of GPR162 affect glucose homeostasis. In conclusion, this study provides evidence linking the orphan GPR162 gene with the regulation of food intake-related behaviour.

Ort, förlag, år, upplaga, sidor
2011.
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-156816OAI: oai:DiVA.org:uu-156816DiVA, id: diva2:433390
Tillgänglig från: 2011-08-09 Skapad: 2011-08-09 Senast uppdaterad: 2022-01-28Bibliografiskt granskad
Ingår i avhandling
1. Functional Characterization of Centrally Expressed Solute Carriers and G Protein-Coupled Receptors
Öppna denna publikation i ny flik eller fönster >>Functional Characterization of Centrally Expressed Solute Carriers and G Protein-Coupled Receptors
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Transmembrane proteins are gatekeepers of the cells; controlling the transport of substrates as well as communicating signals among cells and between the organelles and cytosol. Solute carriers (SLC) and G protein-coupled receptors (GPCR) are the largest family of membrane transporters and membrane receptors respectively. The overall aim of this thesis was to provide a basic understanding of some of the novel SLCs and GPCRs with emphasis on expression, transport property, evolution and probable function.

The first part of the thesis directs towards the study of some novel solute carriers. In an initial study, we provided an overall picture of the sequence relationship and tissue expression of 14 diverse atypical SLCs confirming some of their evolutionary conservation and highly specific expression pattern. The focus then was on the SLC17 family (mainly vesicular proteins) and a novel member named Slc17a9. This study revealed that SLC17 family could be divided into four main phylogenetic clades which were all present before the divergence of the insect lineage with Slc17a9 having the most restricted evolutionary history. Detailed expression study of Slc17a9 in the mouse brain suggests that it is also expressed in some regions important for purinergic neurotransmission. Further, we deorphanised an aminoacid transporter Slc38a7 which was expressed in a majority of neurons in the CNS and showed that it preferably mediate transport of L–glutamine and L–histidine.

The second part of the thesis focuses on the study of two GPCRs belonging to the Rhodopsin superfamily, Gpr162 and Gpr153. A phylogenetic analysis revealed that both Gpr153 and Gpr162 originated from a common ancestor before the radiation of the mammalian lineage. Expression study revealed that Gpr162 had a predominant expression in the CNS and relatively lower expression in the other tissue tested whereas Gpr153 had a more widespread and similar expression pattern in both CNS and peripheral tissues. The functional studies of the two GPCRs were done using the antisense oligodeoxynucleotide knockdown rat model. These studies provided evidence linking the orphan Gpr162 gene with the regulation of food intake– related behaviour whereas Gpr153 gene caused only a slight reduction in food intake.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 51
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 689
Nyckelord
GPCR, SLC, Gpr153, Gpr162, Slc17, Slc38
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Neurovetenskap
Identifikatorer
urn:nbn:se:uu:diva-156832 (URN)978-91-554-8120-9 (ISBN)
Disputation
2011-09-22, B42, BMC, Husargatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2011-09-01 Skapad: 2011-08-09 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Person

Haitina, Tatjana

Sök vidare i DiVA

Av författaren/redaktören
Sreedharan, SmithaJacobsson, Josefin AOlszewski, Pawel KHaitina, TatjanaHammer, JoannaRiserus, UlfLannfelt, LarsFredriksson, RobertSchiöth, Helgi
Av organisationen
Funktionell farmakologiEvolution och utvecklingsbiologiGenomikKlinisk nutrition och metabolismGeriatrik
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 954 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf