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An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance.
Cell Metabolism ( IF 29.0 ) Pub Date : 2020-02-06 , DOI: 10.1016/j.cmet.2020.01.009
Ming He 1 , Hou-Hsien Chiang 1 , Hanzhi Luo 1 , Zhifang Zheng 1 , Qi Qiao 2 , Li Wang 2 , Mingdian Tan 1 , Rika Ohkubo 1 , Wei-Chieh Mu 1 , Shimin Zhao 3 , Hao Wu 2 , Danica Chen 1
Affiliation  

It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown. Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD+-dependent deacetylase and a metabolic sensor. We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance. These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.

中文翻译:

NLRP3炎性体的乙酰化开关调节与衰老相关的慢性炎症和胰岛素抵抗。

有充分的文献证明,可以减缓衰老的速度,但是尚不清楚与衰老相关的条件可以逆转到何种程度。免疫和新陈代谢的界面如何影响糖尿病大流行尚不清楚。在这里,我们显示NLRP3,一种模式识别受体,在巨噬细胞中被乙酰化修饰,并被SIRT2,NAD +依赖性脱乙酰基酶和代谢传感器脱乙酰化。我们已经开发了一种基于细胞的系统,该系统可以模拟与衰老相关的炎症,这是一种定义的共培养系统,可以模拟炎症环境对衰老过程中新陈代谢组织中胰岛素抵抗的影响,以及衰老小鼠模型。并证明SIRT2和NLRP3脱乙酰基可以预防并且可以针对与衰老相关的炎症和胰岛素抵抗进行逆转。
更新日期:2020-02-07
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