Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice.

Détails

ID Serval
serval:BIB_97909F9D8846
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice.
Périodique
American journal of physiology. Endocrinology and metabolism
Auteur(s)
Isken F., Pfeiffer A.F., Nogueiras R., Osterhoff M.A., Ristow M., Thorens B., Tschöp M.H., Weickert M.O.
ISSN
0193-1849
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
295
Numéro
2
Pages
E350-5
Langue
anglais
Résumé
Menopause and premature gonadal steroid deficiency are associated with increases in fat mass and body weight. Ovariectomized (OVX) mice also show reduced locomotor activity. Glucose-dependent-insulinotropic-polypeptide (GIP) is known to play an important role both in fat metabolism and locomotor activity. Therefore, we hypothesized that the effects of estrogen on the regulation of body weight, fat mass, and spontaneous physical activity could be mediated in part by GIP signaling. To test this hypothesis, C57BL/6 mice and GIP-receptor knockout mice (Gipr(-/-)) were exposed to OVX or sham operation (n = 10 per group). The effects on body composition, markers of insulin resistance, energy expenditure, locomotor activity, and expression of hypothalamic anorexigenic and orexigenic factors were investigated over 26 wk in all four groups of mice. OVX wild-type mice developed obesity, increased fat mass, and elevated markers of insulin resistance as expected. This was completely prevented in OVX Gipr(-/-) animals, even though their energy expenditure and spontaneous locomotor activity levels did not significantly differ from those of OVX wild-type mice. Cumulative food intake in OVX Gipr(-/-) animals was significantly reduced and associated with significantly lower hypothalamic mRNA expression of the orexigenic neuropeptide Y (NPY) but not of cocaine-amphetamine-related transcript (CART), melanocortin receptors (MCR-3 and MCR-4), or thyrotropin-releasing hormone (TRH). GIP receptors thus interact with estrogens in the hypothalamic regulation of food intake in mice, and their blockade may carry promising potential for the prevention of obesity in gonadal steroid deficiency.
Mots-clé
Animals, Body Composition/physiology, Eating/physiology, Energy Metabolism/physiology, Female, Gastric Inhibitory Polypeptide/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity/physiology, Nerve Tissue Proteins/biosynthesis, Nerve Tissue Proteins/genetics, Neuropeptide Y/biosynthesis, Neuropeptide Y/genetics, Obesity/etiology, Obesity/genetics, Ovariectomy, RNA, Messenger/biosynthesis, RNA, Messenger/genetics, Receptors, Gastrointestinal Hormone/deficiency, Receptors, Gastrointestinal Hormone/genetics, Receptors, Melanocortin/biosynthesis, Receptors, Melanocortin/genetics, Reverse Transcriptase Polymerase Chain Reaction, Thyrotropin-Releasing Hormone/biosynthesis, Thyrotropin-Releasing Hormone/genetics
Pubmed
Web of science
Création de la notice
15/06/2009 13:47
Dernière modification de la notice
20/08/2019 14:59
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