附件A1与PDZ和LIM域7结合,以抑制脂肪生成和预防肥胖
Lu Fang1, Changjie Liu2, Zong-Zhe Jiang3,4
1The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, 100191, Beijing, China.
Signal transduction and targeted therapy
|August 22, 2024
概括
附件A1 (ANXA1) 通过促进SMAD4降解来抑制脂肪生成,为肥胖提供了一个新的治疗点. 降低ANXA1会加剧肥胖和代谢功能障碍,突出其关键作用.
科学领域:
- 分子生物学分子生物学
- 代谢性疾病研究研究.
- 生物化学 生化学
背景情况:
- 肥胖是一个全球性的健康问题,需要新的治疗策略.
- 素A1 (ANXA1) 具有抗炎性,但其在肥胖中的作用尚不清楚.
- 了解ANXA1的分子病原体对于开发有效的肥胖治疗非常重要.
研究的目的:
- 调查素A1 (ANXA1) 在肥胖和脂肪生成中的作用和机制.
- 确定ANXA1作为代谢障碍的潜在治疗点.
主要方法:
- 从肥胖个体的脂肪组织中分析ANXA1水平.
- 在全身和脂肪细胞特定模型中对ANXA1进行基因操纵.
- 调查ANXA1与MYCBP2,PDLIM7和SMAD4在流体血管部分 (SVF) 的相互作用.
- 评估Ac2-26对脂肪生成和肥胖的影响.
主要成果:
- 肥胖患者的ANXA1水平升高,其缺失会使代谢障碍恶化.
- 通过防止MYCBP2-SMAD4相互作用,从而导致SMAD4降解,ANXA1抑制脂肪生成.
- SMAD4降解降低了PPARγ转录的调节,减少了脂肪细胞的分化.
- 来自ANXA1的Ac2-26具有抗肥胖和抗原作用.
结论:
- ANXA1在调节脂肪生成和预防肥胖方面发挥着至关重要的作用.
- 这项研究阐明了ANXA1通过MYCBP2-PDLIM7-SMAD4途径抑制脂肪生成的分子机制.
- ANXA1及其Ac2-26代表了肥胖干预的有希望的治疗点.
相关概念视频
01:20The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.4K
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...
5.4K
01:25cAMP-dependent Protein Kinase Pathways
6.2K
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,...
6.2K
01:30Regulation of Food Intake
205
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...
205
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
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