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脂质变异基因Agpat2缺陷在Ldlr-/-小鼠中加剧了超脂血症和动脉样硬化
Kenan Peng1, Xin Chen2, Kexin Pei3
1Laboratory of Lipid Metabolism, Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Laboratory Department of Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
Biochimica et biophysica acta. Molecular basis of disease
|August 17, 2023
概括
在小鼠中,阿格帕2缺乏会恶化超脂血症,肝纤维化和动脉样硬化. 这突出了脂肪组织.
科学领域:
- 生物化学和分子生物学
- 心血管研究研究心血管研究
- 代谢疾病 代谢疾病
背景情况:
- 脂肪组织功能障碍与心血管疾病风险有关.
- 肥胖会加剧动脉样硬化,但脂肪组织损失的影响不太了解.
- AGPAT2基因突变会导致先天性泛化脂质变 (CGL),但其在动脉样硬化中的作用尚未报告.
研究的目的:
- 为了研究Agpat2对高脂血症和动脉样硬化的影响.
- 探索脂肪组织在代谢功能障碍和心血管病理中的作用.
主要方法:
- 使用CRISPR/Cas.生成的Agpat2淘汰小鼠使用CRISPR/Cas.
- 交叉Agpat2淘汰赛小鼠与LDL受体淘汰赛小鼠,创建一个双淘汰赛模型.
- 给小鼠食了12周的动脉动脉致死性高脂肪饮食,监测血脂,胰岛素抵抗,肝脏状况和动脉样硬化病变.
主要成果:
- 阿格帕特2缺乏导致严重的脂肪组织损失和脂肪肝.
- 双重淘汰赛小鼠在高脂肪饮食后显著增加了血总胆固醇和甘油三.
- 观察到高血糖,高胰岛素,胰腺小岛扩大,严重的纤维化脂肪肝和加重的动脉样硬化病变.
结论:
- 阿格帕2缺乏会加剧高脂血症,肝纤维化和动脉样硬化.
- 这些发现强调了脂肪组织在调节脂质代谢和心血管健康方面的关键作用.
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