Transgenic Rescue of Adipocyte Glucose-dependent Insulinotropic Polypeptide Receptor Expression Restores High Fat Diet-induced Body Weight Gain

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  • Randi Ugleholdt, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Jens Pedersen, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Maria Rosaria Bassi, Department of International Health Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, DK-1014 Copenhagen, Denmark
  • Ernst-Martin Füchtbauer
  • Signe Marie Jørgensen, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Hanne-Louise Kissow, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Nikolaj Nytofte, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Steen Seier Poulsen, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Mette Marie Rosenkilde, Department of Neuroscience and Pharmacology, University of Copenhagen, DK-2200 Copenhagen , Denmark
  • Yutaka Seino, Department of Diabetes and Clinical Nutrition, Kyoto University, Kyoto 606-8507, Japan
  • Peter Thams, Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
  • Peter Johannes Holst, Department of International Health Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Denmark
  • Jens Juul Holst, Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume286
Issue52
Pages (from-to)44632-44645
Number of pages13
ISSN0021-9258
DOIs
Publication statusPublished - 30 Dec 2011

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