来自富含甘油三醇的脂蛋白的脂解产物诱导骨质母细胞中ATF3压力蛋白
Jennifer M Rutkowsky1, Alice Wong2, Chrisoula A Toupadakis2
1Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA.
概括
高脂肪饮食导致脂质不良,对骨健康产生负面影响. 这项研究表明,富含甘油三的脂蛋白脂解产品通过ATF3诱导骨质细胞应激,但也触发保护性Angptl4.4. 在小鼠中,ATF3删除改善了骨结构.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 骨生物学 骨生物学
背景情况:
- 高脂肪饮食导致脱脂症,其特征是高甘油 (TG) 和富含TG的脂蛋白 (TGRL).
- 脱脂症与心血管疾病,中风,脂肪肝,胰腺炎和骨不良影响有关.
- 脂蛋白脂酶 (LPL) 水解TGRL,产生可能有炎症作用并影响骨细胞 (骨质细胞) 的代谢物.
研究的目的:
- 研究TGRL脂解产品 (TGRL-LP) 对骨质细胞的影响.
- 检查TGRL-LP暴露的骨质细胞中激活转录因子3 (ATF3),反应性氧物种 (ROS) 和血管蛋白类4 (Angptl4) 的作用.
- 评估ATF3缺乏在小鼠的骨后果.
主要方法:
- 用TGRL-LP对MC3T3-E1骨质细胞进行治疗,以测量ATF3,ROS和炎症基因表达 (Ptgs2,IL-6).
- 分析了Angptl4表达及其对TG驱动的ATF3诱导的影响.
- 全球ATF3淘汰赛雄性小鼠使用微CT对骨微架构进行了评估.
主要成果:
- 在骨质细胞中,TGRL-LP显著增加了ATF3表达,Ptgs2,IL-6和ROS.
- TGRL-LP诱导了Angptl4转录,再组合的Angptl4抑制了TG诱导的ATF3表达.
- 缺少ATF3的雄性小鼠表现出增强的椎和皮层骨微架构.
结论:
- TGRL-LP诱导骨质细胞应激,由ATF3上调来证明,可能有助于失脂症的负面骨影响.
- 通过TGRL-LP诱导骨质细胞Angptl4可能提供一种保护机制,防止过度局部脂解.
- 缺少ATF3可以改善骨微架构,这表明ATF3在调解失脂症的骨损伤方面发挥了作用.
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