通过双重YAP-RhoA和PPARγ激活,ARHGEF3协调脂肪细胞缩和分化
Sana Abdul Khaliq1, Shi-Young Park2, Syeda Maham3
1Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea; Department of Molecular Medicine, Gachon University College of Medicine, Incheon 21999, Republic of Korea.
Journal of advanced research
|April 11, 2025
概括
氨酸核酸交换因子3 (ARHGEF3) 调节脂肪细胞的分化和体重. 在小鼠中,ARHGEF3 缺乏会通过调节 YAP-RhoA 信号和 PPARγ 活性来减少体重增加和脂肪细胞大小.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 代谢研究的研究.
背景情况:
- 肥胖是一个主要的全球健康问题.
- 了解脂肪生成和脂肪组织调节至关重要.
- 在这些过程中ARHGEF3的作用在很大程度上是未知的.
研究的目的:
- 研究ARHGEF3在脂肪细胞分化和缩中的功能.
- 确定ARHGEF3对脂肪生成和体重调节的影响.
- 阐明ARHGEF3影响这些过程的分子机制.
主要方法:
- 使用ARHGEF3缺乏的小鼠和野生类型的 littermates 接受高脂肪饮食 (HFD).
- 使用C3H10T1/2细胞进行了全面的代谢表型和体外研究.
- 采用定量PCR,西部涂抹,ChIP,IP,免疫染色和光酶报告测试.
主要成果:
- 在HFD和脂肪生成期间,ARHGEF3的表达在白色脂肪组织中被上调.
- 在小鼠中,ARHGEF3 缺乏导致体重增加和脂肪细胞大小减少.
- ARHGEF3促进了YAP核转位,RhoA促进剂结合,并增强了PPARγ活性,为脂肪生成创造了一个积极的反循环.
结论:
- ARHGEF3 是脂肪细胞分化和缩的关键调节者.
- ARHGEF3协调YAP-RhoA信号,并增强PPARγ活动.
- 准ARHGEF3可能为肥胖和代谢障碍提供新的治疗策略.
相关概念视频
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Master Transcription Regulators
6.8K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.8K
PI3K/mTOR/AKT Signaling Pathway
3.3K
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...
3.3K
GPCRs 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
Regulation 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
cAMP-dependent Protein Kinase Pathways
6.0K
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,...
6.0K


