通过ZBTB9在脂肪细胞中对PPARγ信号的细胞状态依赖调节
bioRxiv : the preprint server for biology
|March 18, 2024
概括
在脂肪细胞生物学中,ZBTB9充当双重调节剂. 它促进成熟细胞中的PPARγ活性,但通过抑制前脂肪细胞中的RB-E2F1信号,抑制脂肪生成,影响肥胖和2型糖尿病.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 分子内分泌学分子内分泌学
背景情况:
- 脂肪细胞对于代谢平衡至关重要.
- 过氧体增殖器激活受体- (PPARγ) 是脂肪细胞分化和功能的关键调节器.
- 通过GWAS研究,ZBTB9与BMI和2型糖尿病 (T2D) 风险有关,并预测与PPARγ相互作用.
研究的目的:
- 研究ZBTB9在脂肪细胞分化和功能中的作用.
- 阐明ZBTB9影响PPARγ活性和脂肪生成的分子机制.
- 了解ZBTB9在代谢平衡中的上下文依赖功能.
主要方法:
- 在3T3-L1细胞和人类前脂肪细胞中进行ZBTB9敲除 (KD).
- 在成熟脂肪细胞中分析PPARγ活性.
- 评估E2F活动和下游基因表达.
- 对RB酸化的研究.
- 使用E2F1抑制剂来阻止ZBTB9缺乏效应.
主要成果:
- ZBTB9积极调节成熟脂肪细胞中的PPARγ活性.
- ZBTB9突击突如其来的增加了前脂肪细胞中的脂肪生成.
- ZBTB9 KD导致E2F活动增加和E2F目标基因的上调.
- 在ZBTB9-KD前脂质细胞中增强了RB酸化.
- 一种E2F1抑制剂逆转了ZBTB9缺乏对脂肪生成的影响.
结论:
- ZBTB9通过RB-E2F1信号通路抑制Pparg表达,作为脂肪生成的负调节剂.
- ZBTB9在脂肪细胞中表现出复杂的,细胞状态依赖的作用,作为PPARγ信号的正和负调节器.
- ZBTB9是一种新的脂肪细胞生物学调节剂,对肥胖和T2D的发病和治疗有潜在的影响.
相关概念视频
01:58Cell Specific Gene Expression
13.6K
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...
13.6K
02:23Master Transcription Regulators
6.9K
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...
6.9K
01:16TGF - β Signaling Pathway
7.3K
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...
7.3K
02:16Transcription Factors
75.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.8K
01:30General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K