巨细胞SUCLA2合的谷氨酸分解通过AMPKK操纵肥胖
Chang Peng1,2,3, Haowen Jiang4, Liya Jing1,5
1State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Nature communications
|February 18, 2025
概括
肥胖症涉及脂肪组织巨细胞 (ATM) 的炎症. 谷氨酸溶解为ATM提供燃料,将AMP激活蛋白激酶 (AMPK) 与炎症和肥胖症联系起来,突出了一个新的治疗点.
科学领域:
- 免疫代谢过程中的免疫代谢.
- 细胞的新陈代谢
- 肥胖病原体的产生
背景情况:
- 肥胖与慢性炎症有关,特别是涉及脂肪组织巨细胞 (ATM).
- 在肥胖期间的ATM中免疫代谢重编程的确切作用尚未完全理解.
研究的目的:
- 阐明谷氨酸溶解和AMP激活蛋白激酶 (AMPK) 在ATM代谢重编程中的作用.
- 研究ATM新陈代谢,炎症和肥胖发展之间的联系.
主要方法:
- 研究了谷氨酸溶解作为ATM中的关键代谢途径.
- 在髓状细胞中利用AMPKα的遗传废除和小鼠中的IL-1β中和.
- 在小鼠中使用siRNA介导的基尼-CoA合成酶子单元β (SUCLA2) 的敲除.
- 在人类ATM中与肥胖状况相关的酸化SUCLA2水平.
主要成果:
- 谷氨酸溶解对ATM能量和基质至关重要,它与AMPK活性和酸盐诱导的IL-1β产生有关.
- 骨髓细胞中的AMPKα缺乏会促进促炎性ATM,损害发热,并加剧饮食引起的肥胖症.
- 在AMPKα缺乏模型中,IL-1β中和或废除减轻了肥胖症.
- 谷氨酸溶解衍生的ATP抑制AMPK,导致SUCLA2激活,酸盐/IL-1β过度生产和肥胖.
- SUCLA2 Knockdown可以减少HFD引起的肥胖;酸化的SUCLA2与人类肥胖有负相关性.
结论:
- 一个谷氨酸溶解/AMPK/SUCLA2/IL-1β轴在ATM中调节炎症和肥胖.
- 准这一轴代表着对肥胖的潜在治疗策略.
相关概念视频
01:25cAMP-dependent Protein Kinase Pathways
6.1K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.1K
01:30Regulation of Food Intake
179
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...
179
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
01:36Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K