相关实验视频
Updated: May 16, 2025
10:28
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
15.3K
在雄性小鼠中,GIPR的激动性和对抗性通过不同的机制降低了体重和食物摄入量
Robert M Gutgesell1,2,3, Ahmed Khalil1,2, Arkadiusz Liskiewicz1,2,4
1Institute for Diabetes and Obesity, Helmholtz, Munich, Germany.
Nature metabolism
|April 29, 2025
概括
葡萄糖依赖的胰岛素型多受体 (GIPR) 反对作用会降低体重和食物摄入量,但需要功能性葡萄糖类-1受体 (GLP-1R) 信号传递. 这与GIPR的激进主义有所不同.
科学领域:
- 代谢调节和神经内分泌学.
- 类激素受体的药理学.
- 控制食欲的分子机制.
背景情况:
- 已知依赖葡萄糖的胰岛素型多受体 (GIPR) 的激活剂和对抗剂可增强因葡萄糖类-1受体 (GLP-1R) 激活作用而导致的体重减轻.
- GIPR激素作用减少体重和食物摄入量独立于GLP-1R信号,通过GABAergicGIPR+神经元起作用.
- GIPR对抗作用影响能量代谢的确切机制尚不清楚.
研究的目的:
- 调查GIPR对抗作用是否通过类似于GIPR对抗作用的机制影响能量代谢.
- 阐明GIPR激动性和对抗性在调节体重和食物摄入中的不同作用.
- 确定GIPR对抗的代谢作用对GLP-1R信号传递和特定神经元群体的依赖性.
主要方法:
- 使用了具有全球或细胞特异缺失Gipr和Glp-1r的转基因小鼠.
- 给药的GIPR抗剂和对体重和食物摄入量的评估影响.
- 在背部阴道综合体中使用单核RNA测序 (snRNA-seq).
- 分析了与突触可塑性相关的基因表达.
主要成果:
- 在全球缺乏Gipr或Glp-1r的小鼠中,GIPR对抗的体重和食物摄入效应被废除.
- 这些效应在Gipr损失的小鼠中保留,特别是在中央GABAergic神经元或外围神经元中.
- 单核RNA测序揭示了GIPR激动性和对抗性在背部阴道综合体中的对立作用,对抗性模仿GLP-1R信号传递.
- GIPR对抗性和GLP-1R对抗性都调节了参与突触可塑性的基因.
结论:
- 通过不同的机制,GIPR的激动性和对抗性会降低体重.
- GIPR对抗对体重和食物摄入的影响取决于功能GLP-1R信号传递.
- 与GIPR激动性不同,GIPR对抗性的代谢作用不是由中央GABAergicGIPR+神经元调解的,而是依赖GLP-1R通路.
相关概念视频
01:30Regulation of Food Intake
155
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
155
01:09GPCRs Regulate Adenylyl Cylase Activity
5.1K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.1K
01:24Glucagon-like Receptor Agonists
272
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
272
01:40Hormonal Regulation
43.0K
Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
43.0K