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The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling
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 t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035082/ https://www.ncbi.nlm.nih.gov/pubmed/33571454 http://dx.doi.org/10.1016/j.cmet.2021.01.015 |
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author | Zhang, Qian Delessa, Challa Tenagne Augustin, Robert Bakhti, Mostafa Colldén, Gustav Drucker, Daniel J. Feuchtinger, Annette Caceres, Cristina Garcia Grandl, Gerald Harger, Alexandra Herzig, Stephan Hofmann, Susanna Holleman, Cassie Lynn Jastroch, Martin Keipert, Susanne Kleinert, Maximilian Knerr, Patrick J. Kulaj, Konxhe Legutko, Beata Lickert, Heiko Liu, Xue Luippold, Gerd Lutter, Dominik Malogajski, Emilija Medina, Marta Tarquis Mowery, Stephanie A. Blutke, Andreas Perez-Tilve, Diego Salinno, Ciro Sehrer, Laura DiMarchi, Richard D. Tschöp, Matthias H. Stemmer, Kerstin Finan, Brian Wolfrum, Christian Müller, Timo D. |
author_facet | Zhang, Qian Delessa, Challa Tenagne Augustin, Robert Bakhti, Mostafa Colldén, Gustav Drucker, Daniel J. Feuchtinger, Annette Caceres, Cristina Garcia Grandl, Gerald Harger, Alexandra Herzig, Stephan Hofmann, Susanna Holleman, Cassie Lynn Jastroch, Martin Keipert, Susanne Kleinert, Maximilian Knerr, Patrick J. Kulaj, Konxhe Legutko, Beata Lickert, Heiko Liu, Xue Luippold, Gerd Lutter, Dominik Malogajski, Emilija Medina, Marta Tarquis Mowery, Stephanie A. Blutke, Andreas Perez-Tilve, Diego Salinno, Ciro Sehrer, Laura DiMarchi, Richard D. Tschöp, Matthias H. Stemmer, Kerstin Finan, Brian Wolfrum, Christian Müller, Timo D. |
author_sort | Zhang, Qian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8035082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80350822021-04-15 The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling Zhang, Qian Delessa, Challa Tenagne Augustin, Robert Bakhti, Mostafa Colldén, Gustav Drucker, Daniel J. Feuchtinger, Annette Caceres, Cristina Garcia Grandl, Gerald Harger, Alexandra Herzig, Stephan Hofmann, Susanna Holleman, Cassie Lynn Jastroch, Martin Keipert, Susanne Kleinert, Maximilian Knerr, Patrick J. Kulaj, Konxhe Legutko, Beata Lickert, Heiko Liu, Xue Luippold, Gerd Lutter, Dominik Malogajski, Emilija Medina, Marta Tarquis Mowery, Stephanie A. Blutke, Andreas Perez-Tilve, Diego Salinno, Ciro Sehrer, Laura DiMarchi, Richard D. Tschöp, Matthias H. Stemmer, Kerstin Finan, Brian Wolfrum, Christian Müller, Timo D. Cell Metab Article 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. Cell Press 2021-04-06 /pmc/articles/PMC8035082/ /pubmed/33571454 http://dx.doi.org/10.1016/j.cmet.2021.01.015 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Qian Delessa, Challa Tenagne Augustin, Robert Bakhti, Mostafa Colldén, Gustav Drucker, Daniel J. Feuchtinger, Annette Caceres, Cristina Garcia Grandl, Gerald Harger, Alexandra Herzig, Stephan Hofmann, Susanna Holleman, Cassie Lynn Jastroch, Martin Keipert, Susanne Kleinert, Maximilian Knerr, Patrick J. Kulaj, Konxhe Legutko, Beata Lickert, Heiko Liu, Xue Luippold, Gerd Lutter, Dominik Malogajski, Emilija Medina, Marta Tarquis Mowery, Stephanie A. Blutke, Andreas Perez-Tilve, Diego Salinno, Ciro Sehrer, Laura DiMarchi, Richard D. Tschöp, Matthias H. Stemmer, Kerstin Finan, Brian Wolfrum, Christian Müller, Timo D. The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title | The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title_full | The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title_fullStr | The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title_full_unstemmed | The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title_short | The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling |
title_sort | glucose-dependent insulinotropic polypeptide (gip) regulates body weight and food intake via cns-gipr signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035082/ https://www.ncbi.nlm.nih.gov/pubmed/33571454 http://dx.doi.org/10.1016/j.cmet.2021.01.015 |
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