Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain
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Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain. / Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hannelouise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul.
In: The Journal of Biological Chemistry, Vol. 286, No. 52, 12.2011, p. 44632-44645.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain
AU - Ugleholdt, Randi
AU - Pedersen, Jens
AU - Bassi, Maria Rosaria
AU - Füchtbauer, Ernst-Martin
AU - Jørgensen, Signe Marie
AU - Kissow, Hannelouise
AU - Nytofte, Nikolaj
AU - Poulsen, Steen Seier
AU - Rosenkilde, Mette Marie
AU - Seino, Yutaka
AU - Thams, Peter
AU - Holst, Peter Johannes
AU - Holst, Jens Juul
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Adipocytes
KW - Adipogenesis
KW - Animals
KW - Dietary Fats
KW - Gastric Inhibitory Polypeptide
KW - Humans
KW - Insulin
KW - Insulin-Secreting Cells
KW - Mice
KW - Mice, Knockout
KW - Obesity
KW - Receptors, Gastrointestinal Hormone
KW - Receptors, Peptide
KW - Transgenes
KW - Weight Gain
U2 - 10.1074/jbc.M111.311779
DO - 10.1074/jbc.M111.311779
M3 - Journal article
C2 - 22027838
VL - 286
SP - 44632
EP - 44645
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 52
ER -
ID: 38321432