在巨细胞中由炎症酶驱动的甲醇化会在衰老过程中减弱脂解
Christina D Camell1,2, Jil Sander3, Olga Spadaro1,2
1Department of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|September 28, 2017
概括
衰老会通过降低上腺素的可用性来减轻脂肪的分解 (脂解). 在巨细胞中向NLRP3炎症酶和单胺氧化酶A (MAOA) 恢复脂解,在衰老中提供代谢健康益处.
科学领域:
- 免疫学
- 代谢过程
- 老龄化研究
背景情况:
- 随着年龄的增长, catecholamine 诱导的脂解对能量产生至关重要.
- 这种与年龄相关的下降与内脏脂肪,运动能力下降和温度调节受损有关.
- 尽管脂肪细胞的信号传递正常,但衰老中脂肪溶解受损的确切机制尚不清楚.
研究的目的:
- 调查脂肪组织巨细胞在与年龄相关的脂解减少中的作用.
- 识别衰老中脂肪动员受损的分子途径.
- 探索与年龄相关的代谢功能障碍的潜在治疗点.
主要方法:
- 老鼠脂肪组织巨细胞的全转录组分析.
- 对NLRP3炎症组分和特定基因 (GDF3,MAOA) 的遗传删除.
- 测量脂解,上腺素水平和关键的脂解酶 (ATGL,HSL).
主要成果:
- 衰老通过NLRP3炎症体对脂肪巨中的甲醇胺降解基因进行上调.
- 通过降低GDF3和MAOA的调节,NLRP3的删除恢复了脂解.
- 抑制MAOA可以逆转与年龄相关的上腺素下降并恢复脂解.
结论:
- 脂肪组织的巨细胞通过甲醇胺降解来调节与年龄相关的脂解损伤.
- 针对神经免疫代谢轴,特别是NLRP3和MAOA,可以恢复脂解.
- 这项研究提出了减轻年龄相关代谢衰退和炎症的新方法.
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