通过线粒体的pyruvate载体分离性取决于性别的脂肪葡萄糖
Christopher E Shannon1,2, Terry Bakewell2, Marcel J Fourcaudot2
1UCD Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland.
bioRxiv : the preprint server for biology
|May 27, 2024
概括
线粒体的酸盐载体 (MPC) 对于脂肪代谢至关重要,特别是在女性身上. MPC 干扰会影响雌性脂肪组织中的葡萄糖使用,但在小鼠中保持整体代谢健康.
科学领域:
- 代谢途径 代谢途径
- 线粒体功能 线粒体功能
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 线粒体的酸盐载体 (MPC) 是一个关键的代谢调节器.
- 脂肪组织功能障碍是肥胖和心脏代谢疾病的核心原因.
- MPC在脂肪组织适应代谢压力的作用尚不清楚.
研究的目的:
- 研究MPC在脂肪组织适应饮食挑战中的作用.
- 确定MPC对脂肪代谢和葡萄糖处理在脂肪细胞和整个动物的影响.
- 探索MPC介导的脂肪组织代谢的性别特异性差异.
主要方法:
- 在3T3L1脂肪细胞和小鼠脂肪扩展体中抑制MPC的药理和遗传学.
- 对甘油三合成,脂质生成和甘油蛋白生成的分析.
- 在人类脂肪组织中评估MPC表达.
- 在各种饮食条件下,生成和代谢表型化脂肪细胞特异的MPC1淘汰赛小鼠 (Mpc1AD-/-).
- 在体内分析中使用了放射性标记的标记物和GC/MS代谢量.
主要成果:
- 抑制MPC会损害皮鲁酸盐在脂肪细胞中的脂质和甘油三的整合.
- 人体脂肪MPC表达与代谢功能障碍相反相关.
- 在小鼠中,脂质特异性MPC删除阻止了酸盐转化为甘油三的过程.
- 在接受无脂肪饮食的雌性小鼠中,MPC删除限制了葡萄糖的纳入脂肪甘油三化物,伴有性别特异的代谢变化.
- 在MPC缺乏的小鼠中,无论性别如何,全身脂肪和代谢健康都保持不变.
结论:
- 脂肪组织在线粒体驱动的甘油三合成中表现出性别特异性差异.
- 在脂质限制期间,MPC在女性脂肪组织中对葡萄糖分裂至脂质合成中发挥着关键作用.
- MPC是代谢疾病的潜在治疗标,在男性和女性代谢中发挥着不同的作用.
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