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空气污染通过HDAC9和KDM2B的表观遗传调节调节棕色脂肪组织功能
Rengasamy Palanivel1, Jean-Eudes Dazard1, Bongsoo Park2
1Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
JCI insight
|September 23, 2025
概括
暴露于空气污染,特别是细颗粒物 (PM2.5),会对新陈代谢和棕色脂肪组织 (BAT) 功能产生负面影响. 这项研究揭示了PM2.5改变了BAT基因表达和表观遗传修饰,导致胰岛素抵抗.
科学领域:
- 环境健康 环境健康
- 代谢性疾病 代谢性疾病
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 空气污染越来越多地与胰岛素耐药性和2型糖尿病等代谢障碍有关.
- 颗粒物 (PM2.5) 是空气污染的主要组成部分,已知对健康的影响.
研究的目的:
- 研究PM2.5吸入对新陈代谢和棕色脂肪组织 (BAT) 功能的影响.
- 在BAT中阐明PM2.5诱导的代谢功能障碍背后的分子机制.
主要方法:
- 全身吸入暴露于缩的PM2.5或过空气24周.
- 使用18F-氧葡萄糖正子发射断层扫描对葡萄糖吸收的评估.
- 在BAT中对差异甲基化区域,染色质可访问性和基因表达的分析.
- 染色体免疫沉 (ChIP) 测试以确认蛋白质-DNA相互作用.
主要成果:
- 暴露于PM2.5会损害新陈代谢和改变BAT功能,影响热生成,氧化还原应激,脂质沉积和纤维化.
- 在PM2.5暴露后的BAT中观察到显著的差异甲基化和染色质重塑.
- 组织素脱乙酶HDAC9和组织素脱甲酶KDM2B被确定为PM2.5诱导的BAT变化中的关键调节剂.
- 降低Hdac9/Kdm2b改善了BAT代谢,而过度表达则损害了它.
结论:
- 暴露于PM2.5会诱导棕色脂肪组织的有害表观遗传和转录变化,导致代谢功能障碍.
- HDAC9和KDM2B在调解PM2.5对BAT和整体新陈代谢的不良影响方面发挥着至关重要的作用.
- 这些发现为空气污染如何导致胰岛素耐药性和2型糖尿病的病变产生提供了机械的见解.
相关概念视频
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...

