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  • Zhang, Qian (author)

The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Elsevier BV,2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-194271
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-194271URI
  • https://doi.org/10.1016/j.cmet.2021.01.015DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.

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  • Delessa, Challa Tenagne (author)
  • Augustin, Robert (author)
  • Bakhti, Mostafa (author)
  • Colldén, Gustav (author)
  • Drucker, Daniel J. (author)
  • Feuchtinger, Annette (author)
  • Garcia Caceres, Cristina (author)
  • Grandl, Gerald (author)
  • Harger, Alexandra (author)
  • Herzig, Stephan (author)
  • Hofmann, Susanna (author)
  • Holleman, Cassie Lynn (author)
  • Jastroch, MartinStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)maja7434 (author)
  • Keipert, SusanneStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)suke3968 (author)
  • Kleinert, Maximilian (author)
  • Knerr, Patrick J. (author)
  • Kulaj, Konxhe (author)
  • Legutko, Beata (author)
  • Lickert, Heiko (author)
  • Liu, Xue (author)
  • Luippold, Gerd (author)
  • Lutter, Dominik (author)
  • Malogajski, Emilija (author)
  • Tarquis Medina, Marta (author)
  • Mowery, Stephanie A. (author)
  • Blutke, Andreas (author)
  • Perez-Tilve, Diego (author)
  • Salinno, Ciro (author)
  • Sehrer, Laura (author)
  • DiMarchi, Richard D. (author)
  • Tschöp, Matthias H. (author)
  • Stemmer, Kerstin (author)
  • Finan, Brian (author)
  • Wolfrum, Christian (author)
  • Müller, Timo D. (author)
  • Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

Related titles

  • In:Cell Metabolism: Elsevier BV33:4, s. 833-8441550-41311932-7420

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