小柯机器人

美国加州大学伯克利分校Danica Chen研究组研究发现NLRP3炎性小体的乙酰化开关调节衰老相关的慢性炎症和胰岛素抵抗。该成果在线发表在2020年2月6日的《细胞—代谢》上。

他们表示NLRP3是一种模式识别受体，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。他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，这是一种被定义的共培养系统，可以模拟炎症环境对衰老过程新陈代谢组织中胰岛素抵抗效应，以及衰老小鼠模型。并证明SIRT2和NLRP3脱乙酰化可以预防并且可以对与衰老相关的炎症和胰岛素抵抗进行逆转。这些结果确定了NLRP3炎症小体的乙酰化开关失调是衰老相关慢性炎症的起源，并突出了衰老相关的慢性炎症和胰岛素抵抗的可逆性。

据悉，有充分的文献证明，衰老速度可以被减缓，但是衰老相关的条件可以被逆转到何种程度尚不清楚。免疫和新陈代谢的界面如何影响糖尿病流行基本未知。

附：英文原文

Title: An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance

Author: Ming He, Hou-Hsien Chiang, Hanzhi Luo, Zhifang Zheng, Qi Qiao, Li Wang, Mingdian Tan, Rika Ohkubo, Wei-Chieh Mu, Shimin Zhao, Hao Wu, Danica Chen

Issue&Volume: February 06, 2020

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

DOI: 10.1016/j.cmet.2020.01.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30009-7

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx