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

• DOI: 10.1016/j.cmet.2021.01.015
• Publication Date: 2021-02-10T16:29:40Z
• Authors: Qian Zhang; Challa Tenagne De...; Robert Augustin; Mostafa Bakhti; Gustav Colldén; Daniel J. Drucker; Annette Feuchtinger; Cristina Garcia C...; Gerald Grandl; Alexandra Harger; Stephan Herzig; Susanna Hofmann; Cassie Lynn Holleman; Martin Jastroch; Susanne Keipert; Maximilian Kleinert; Patrick J. Knerr; Konxhe Kulaj; Beata Legutko; Heiko Lickert; Xue Liu; Gerd Luippold; Dominik Lutter; Emilija Malogajski; Marta Tarquis Medina; Stephanie A. Mowery; Andreas Blutke; Diego Perez-Tilve; Ciro Salinno; Laura Sehrer; Richard D. DiMarchi; Matthias H. Tschöp; Kerstin Stemmer; Brian Finan; Christian Wolfrum; Timo D. Müller
• Keywords: Gastric inhibitory polypeptide

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