P38α MAPK 协调线粒体适应骨肌肉中的热量余
Liron Waingerten-Kedem1, Sharon Aviram1, Achinoam Blau1
1Department of Biochemistry, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Bat Galim, Haifa 31096, Israel.
International journal of molecular sciences
|July 27, 2024
概括
在高脂肪饮食期间,骨肌肉中p38α活性降低会使胰岛素抵抗和代谢不灵活性恶化. 这导致线粒体功能障碍和营养代谢受损,突出表现p38αα.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 线粒体功能 线粒体功能
- 胰岛素耐药性 胰岛素耐药性是一种
背景情况:
- 过多的卡路里摄入会导致线粒体过载,代谢不灵活和胰岛素抵抗.
- 骨肌肉在葡萄糖和脂肪代谢中起着关键作用.
研究的目的:
- 调查p38α激酶在骨肌肉适应高脂肪饮食 (HFD) 的作用.
- 确定减弱的p38α活性如何影响葡萄糖和脂肪代谢以及线粒体功能.
主要方法:
- 使用了一种小鼠模型,p38α活性减弱 (p38αAF) 被食高脂肪饮食.
- 评估体重增加,胰岛素耐受性,血清胰岛素水平和骨肌肉胰岛素信号.
- 分析了肌肉代谢物,线粒体形态和肌管呼吸能力.
主要成果:
- p38αAF小鼠的体重增加,胰岛素水平提高,胰岛素耐受性受损.
- 在p38αAF小鼠的骨肌中表现出缺陷的胰岛素信号传递,降低了糖解和β-氧化,以及线粒体异常.
- 来自p38αAF小鼠的肌管已降低了线粒体呼吸能力,并改变了营养物质氧化途径.
结论:
- p38α对于骨肌肉适应热量余至关重要,促进线粒体生物发生和调节营养氧化.
- 减弱的p38α活性导致线粒体过载,代谢不灵活性和胰岛素抵抗增加.
- 准p38α可能为与肥胖相关的代谢障碍提供治疗策略.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
MAPK Signaling Cascades
5.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
Cell Specific Gene Expression
13.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.5K


