Vaccination against GIP for the treatment of obesity.
BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect...
Main Authors: | , , , , , , |
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Format: | Journal article |
Language: | English |
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Public Library of Science
2008
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author | Fulurija, A Lutz, T Sladko, K Osto, M Wielinga, P Bachmann, M Saudan, P |
author_facet | Fulurija, A Lutz, T Sladko, K Osto, M Wielinga, P Bachmann, M Saudan, P |
author_sort | Fulurija, A |
collection | OXFORD |
description | BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(-/-)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity. METHODOLOGY/PRINCIPAL FINDINGS: In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance. CONCLUSIONS/SIGNIFICANCE: This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans. |
first_indexed | 2024-03-07T04:23:48Z |
format | Journal article |
id | oxford-uuid:cbef526f-e78a-47b6-9928-beb9bf8f6414 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:23:48Z |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | dspace |
spelling | oxford-uuid:cbef526f-e78a-47b6-9928-beb9bf8f64142022-03-27T07:18:17ZVaccination against GIP for the treatment of obesity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cbef526f-e78a-47b6-9928-beb9bf8f6414EnglishSymplectic Elements at OxfordPublic Library of Science2008Fulurija, ALutz, TSladko, KOsto, MWielinga, PBachmann, MSaudan, P BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(-/-)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity. METHODOLOGY/PRINCIPAL FINDINGS: In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance. CONCLUSIONS/SIGNIFICANCE: This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans. |
spellingShingle | Fulurija, A Lutz, T Sladko, K Osto, M Wielinga, P Bachmann, M Saudan, P Vaccination against GIP for the treatment of obesity. |
title | Vaccination against GIP for the treatment of obesity. |
title_full | Vaccination against GIP for the treatment of obesity. |
title_fullStr | Vaccination against GIP for the treatment of obesity. |
title_full_unstemmed | Vaccination against GIP for the treatment of obesity. |
title_short | Vaccination against GIP for the treatment of obesity. |
title_sort | vaccination against gip for the treatment of obesity |
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