Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

Abstract

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.

• Authors: Randi Ugleholdt, Jens Pedersen, Maria Rosaria Bassi, Ernst-Martin Füchtbauer, Signe Marie Jørgensen, Hanne-Louise Kissow, Nikolaj Nytofte, Steen Seier Poulsen, Mette Marie Rosenkilde, Yutaka Seino, Peter Thams, Peter Johannes Holst, Jens Juul Holst
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 52 Pg. 44632-45 (Dec 30 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 22027838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Insulin
• Receptors, Gastrointestinal Hormone
• Receptors, Peptide
• Gastric Inhibitory Polypeptide
• gastric inhibitory polypeptide receptor

Topics

• Adipocytes (metabolism)
• Adipogenesis (genetics)
• Animals
• Dietary Fats (adverse effects, pharmacology)
• Gastric Inhibitory Polypeptide (genetics, metabolism)
• Humans
• Insulin (genetics, metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (metabolism)
• Mice
• Mice, Knockout
• Obesity (genetics, metabolism)
• Receptors, Gastrointestinal Hormone (genetics, metabolism)
• Receptors, Peptide (genetics, metabolism)
• Transgenes
• Weight Gain