期刊
CELL METABOLISM
卷 33, 期 4, 页码 833-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2021.01.015
关键词
-
资金
- Alexander von Humboldt Foundation
- Helmholtz Alliance ICEMED
- Helmholtz Initiative on Personalized Medicine iMed by Helmholtz Association
- German Research Foundation [TRR152, TRR296, SFB1123]
- European Research Council (ERC AdG HypoFlam) [695054]
- European Research Council (ERC STG) [757393]
- German Center for Diabetes Research (DZD e.V.)
- CIHR [154321]
- BBDC-Novo Nordisk Chair in Incretin Biology
- Sinai Health System-Novo Nordisk Foundation Fund in Gut Hormone Physiology
- Helmholtz cross-program topic Metabolic Dysfunction
- European Research Council (ERC) [757393] Funding Source: European Research Council (ERC)
The activation or inhibition of the glucose-dependent insulinotropic polypeptide receptor (GIPR) for the treatment of obesity remains uncertain. Studies show that CNS Gipr plays a key role in controlling energy metabolism, with activation or inhibition having significant effects on body weight and glucose metabolism.
Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据