蛋白质体功能下降 恶化 细胞内膜网膜 压力诱导 肥胖脂肪组织慢性炎症
Shimpei Nakagawa1, Aya Fukui-Miyazaki2, Takuma Yoshida1
1Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
The American journal of pathology
|February 29, 2024
概括
蛋白酶体功能受损会增加细胞内网膜 (ER) 的压力,导致白色脂肪组织 (WAT) 炎症. 这种与年龄相关的衰退可能与老年人肥胖有关.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 免疫学 免疫学 免疫学
背景情况:
- 低度慢性炎症与衰老和与年龄相关的疾病有关.
- 与肥胖相关的白脂肪组织 (WAT) 炎症因衰老而加剧.
- 与衰老相关的WAT炎症的分子机制尚不清楚.
研究的目的:
- 研究脂肪细胞衰老对WAT炎症的影响,在小鼠模型中,蛋白质体功能减弱.
- 阐明蛋白质酶体损伤和内质网膜 (ER) 应激在WAT炎症中的作用.
主要方法:
- 使用转基因小鼠,蛋白质体子单元β5t活性受损,表现出与年龄相关的表型.
- 对患有蛋白质体功能障碍的小鼠进行高脂肪饮食.
- 分析了WAT炎症,巨细胞透和脂肪基因表达.
- 在3T3-L1细胞中研究了ER压力标志物和皮细胞素诱导,这些细胞具有受损的蛋白质体活性.
主要成果:
- 蛋白质体功能障碍和高脂肪饮食增加了WAT炎症和M1-类巨细胞透.
- 观察到高水平的单细胞化学吸引蛋白-1,等离子体激活剂抑制剂-1和瘤缩因子-α.
- 受损的蛋白质体活动激活了ER应激通路,并诱导了脂肪细胞中的炎症前类细胞因子.
结论:
- 蛋白质体活性受损通过ER压力和随后的炎症途径促进WAT炎症.
- 与年龄相关的蛋白质体功能下降可能会导致老年人与肥胖相关的炎症.
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