在Mc4r表达细胞中的CRTC1对于周围新陈代谢和系统能量恒温是必需的
Haruka Miyamori1, Takumi Yokokawa1, Motoki Miyakita1
1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Diabetes
|September 12, 2024
概括
在表达黑色皮质素-4受体 (Mc4r) 的细胞中,CREBP调节的转录协活性剂-1 (CRTC1) 对能量平衡至关重要. 它的缺乏会导致肥胖和代谢功能障碍,因为它会损害能量消耗和热生成.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 神经内分泌学神经内分泌学
- 分子生物学分子生物学
背景情况:
- 黑色皮质-4受体 (Mc4r) 通过cAMP信号调节能量平衡.
- 通过CREBP调节的转录协激活剂-1 (CRTC1) 影响神经元可塑性和能量恒温.
- CRTC1活动依赖于cAMP,这表明它在黑色素皮质蛋白通路中起作用.
研究的目的:
- 研究CRTC1在Mc4r表达细胞中在调节能量代谢中的生理作用.
- 阐明CRTC1对黑色皮质蛋白系统控制能量平衡的贡献.
主要方法:
- 产生具有CRTC1缺陷的小鼠,特别是表达Mc4r细胞的小鼠.
- 评估代谢参数,包括体重,耐葡萄糖,胰岛素耐药性和脂质概况.
- 测量系统能量消耗,热生成和适应黑色皮质激素激动剂.
- 对关键代谢组织中与热生和脂生程序相关的基因表达的分析.
主要成果:
- 在表达Mc4r细胞中的CRTC1缺乏导致了适度的肥胖,葡萄糖不耐受,胰岛素耐药性,高胰岛素血症和高脂血症.
- 小鼠的系统能量消耗降低,热生成受损.
- 作为对黑色皮质素激动剂的反应,能量消耗和食物摄入的适应被抑制.
- 棕色脂肪组织和骨肌肉中的热生成和氧化途径受损.
- 肝脏和白色脂肪组织中的脂质生成程序得到了增强.
结论:
- 在Mc4r表达细胞中的CRTC1在调节系统能量平衡方面发挥着重要作用.
- 缺少CRTC1会破坏能量消耗,热生成和代谢平衡.
- 这些发现为由黑色皮质素系统控制的能量平衡的分子机制提供了新的见解.
相关概念视频
01:46Electron Transport Chain: Complex I and II
12.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
12.2K
01:31Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K