Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.
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.
Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Randi
R
Ugleholdt
Jens
J
Pedersen
Maria Rosaria
MR
Bassi
Ernst-Martin
EM
Füchtbauer
Signe Marie
SM
Jørgensen
Hanne-Louise
HL
Kissow
Nikolaj
N
Nytofte
Steen Seier
SS
Poulsen
Mette Marie
MM
Rosenkilde
Yutaka
Y
Seino
Peter
P
Thams
Peter Johannes
PJ
Holst
Jens Juul
JJ
Holst
D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D015430:Weight Gain
D004041:Dietary Fats; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D018000:Receptors, Peptide; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor