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Zhang, Q. ; Delessa, C.T.* ; Augustin, R.* ; Bakhti, M. ; Collden, G. ; Drucker, D.J.* ; Feuchtinger, A. ; García-Cáceres, C. ; Grandl, G. ; Harger, A. ; Herzig, S. ; Hofmann, S.M. ; Holleman, C.L. ; Jastroch, M.* ; Keipert, S.* ; Kleinert, M. ; Knerr, P.J.* ; Kulaj, K. ; Legutko, B. ; Lickert, H. ; Liu, X. ; Luippold, G.* ; Lutter, D. ; Malogajski, E. ; Tarquis Medina, M. ; Mowery, S.A.* ; Blutke, A. ; Perez-Tilve, D.* ; Salinno, C. ; Sehrer, L. ; DiMarchi, R.D.* ; Tschöp, M.H. ; Stemmer, K. ; Finan, B.* ; Wolfrum, C.* ; Müller, T.D.

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

Cell Metab. 33, 833-844.e5 (2021)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Cns ; Gip ; Gipr Cns Ko ; Body Weight ; Diet-induced Obesity ; Food Intake ; Glucose Metabolism ; Incretin ; Type 2 Diabetes; Gastric-inhibitory Polypeptide; Lipoprotein-lipase; Glucagon
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 33, Issue: 4, Pages: 833-844.e5 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Grants Helmholtz cross-program topic Metabolic Dysfunction
Helmholtz Alliance ICEMED
Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association
German Research Foundation
European Research Council (ERC AdG HypoFlam)
European Research Council (ERC STG)
German Center for Diabetes Research (DZD e.V.)
CIHR
BBDC-Novo Nordisk Chair in Incretin Biology
Sinai Health System-Novo Nordisk Foundation Fund in Gut Hormone Physiology
Alexander von Humboldt Foundation