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在ANGPTL4水平和功能的性二态的特征
Mingjuan Deng1, Sander Kersten2
1Nutrition, Metabolism, and Genomics group, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
Journal of lipid research
|March 2, 2024
概括
雄性小鼠显示较高的angiopoietin-like 4 (ANGPTL4) 水平和脂质效应比雌性. 然而,在两种性别中,ANGPTL4 失活的好处是相似的,这表明 ANGPTL4 是心血管风险的可行的治疗点.
科学领域:
- 内分泌学和新陈代谢学
- 心血管研究研究心血管研究
- 分子生物学分子生物学
背景情况:
- 血管类4 (ANGPTL4) 是血甘油三和心血管风险的关键调节剂.
- 临床前研究主要使用雄性小鼠,在了解ANGPTL4的性二态性方面存在差距.
- 对于有针对性的药理干预来说,调查性二态度至关重要.
研究的目的:
- 调查ANGPTL4mRNA和蛋白质水平中的性二态以及其功能影响.
- 用转基因和淘汰赛小鼠模型探索ANGPTL4在肝脏禁食新陈代谢中的作用.
- 为了比较小鼠和人类的不同性别的ANGPTL4调节和功能.
主要方法:
- 在雄性和雌性小鼠和人类组织 (肝脏,脂肪) 中对ANGPTL4mRNA和蛋白质水平的比较分析.
- 使用Angptl4-转基因和Angptl4-/-小鼠进行功能研究,以评估血脂调节.
- 对人类ANGPTL4功能丧失变异的遗传分析和对快速吃饭的小鼠肝脏基因表达变化的评估.
主要成果:
- 与雌性相比,雄性小鼠表现出更高的肝脏和脂肪ANGPTL4水平,以及对遗传ANGPTL4调节的更强的反应.
- 人体组织在ANGPTL4水平中显示出最小的性二态,但女性的ANGPTL8水平更高.
- ANGPTL4 缺乏导致雌性小鼠的脂肪LPL增加,由 ANGPTL4 过度表达逆转;人类遗传 ANGPTL4 变异在两性中都显示出类似的甘油三降低.
结论:
- ANGPTL4水平及其对血脂物的影响在小鼠中显示性变态,但在人类中不显著.
- 预计ANGPTL4失活会为男性和女性的甘油三降低提供类似的代谢益处.
- 脂肪组织的ANGPTL8表达具有高度的两性变异性,在女性中观察到更高的水平.
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