Vaccination against GIP for the Treatment of Obesity

Alma Fulurija, T.A. Lutz, K. Sladko, M. Osto, P.Y. Wielinga, M.F. Bachmann, P. Saudan

    Research output: Contribution to journalArticle

    76 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)1-11
    JournalPLoS One
    Volume3
    Issue number9
    DOIs
    Publication statusPublished - 2008

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