补充因子5的删除在肥胖的雄性但不是雌性小鼠中放大了葡萄糖不耐受性
Nathan C Winn1, Vitrag S Patel1, Joslin A Blair1
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.
American journal of physiology. Endocrinology and metabolism
|August 23, 2023
概括
补充因子5 (C5) 缺乏在肥胖的雄性小鼠中恶化了葡萄糖耐受性,但不是雌性小鼠. 这项研究引入了一个新的C5零鼠标模型来研究C5的C5.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢障碍 代谢障碍 代谢障碍
- 遗传学 是一个遗传学.
背景情况:
- 补充因子5 (C5) 激活与肥胖相关的代谢障碍有关,但其致病作用尚不清楚.
- 现有的C5无基因小鼠模型已经显示出非目标基因突变,需要开发改进的基因线.
研究的目的:
- 使用CRISPR-Cas9基因编辑生成一个新的C5无 (C5-/-) 鼠标模型.
- 研究C5在与肥胖相关的代谢功能障碍,特别是葡萄糖耐受性和炎症中的作用.
主要方法:
- 通过CRISPR-Cas9基因编辑生成C5-/-小鼠.
- 给野生型 (WT) 和C5-/-小鼠提供22周的低脂肪饮食 (LFD) 或高脂肪饮食 (HFD).
- 评估体重,耐葡萄糖,胰岛素水平,脂肪组织炎症,脂肪细胞大小,脂肪肝和肝炎.
- 对内毒素暴露的系统性细胞因子反应的评估.
主要成果:
- 在两种饮食中的基因型之间没有观察到体重增加的显著差异.
- 与WT对照组相比,C5-/-雄性小鼠在肥胖条件下表现出较差的葡萄糖耐受性;雌性小鼠没有显示差异.
- 饮食诱导的肥胖男性C5-/-小鼠的胰岛素度较低;脂肪组织或肝脏炎症没有发现差异.
- C5-/-小鼠对内毒素的系统性细胞因子反应降低.
结论:
- 在男性肥胖小鼠中,C5的损失会以性别依赖的方式加剧葡萄糖不耐受.
- 将C5缺乏与葡萄糖不耐受性联系在一起的潜在机制需要进一步研究.
- 新生成的C5无鼠标模型是研究肥胖相关疾病中的补充激活的宝贵工具.
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