加州大学圣地亚哥分校Michael Karin课题组发现，胆碱摄取和代谢可以调节巨噬细胞IL1β和IL18的产生。 2019年6月，国际知名学术期刊《Cell Metabolism》发表了这一成果。

该研究组发现Toll样受体(TLR)的激活，通过诱导胆碱转运体CTL1提高巨噬细胞和小胶质细胞对胆碱的摄取。阻止CTL1表达或抑制胆碱磷酸化减弱被刺激巨噬细胞中NLRP3炎症体的激活和IL1β和IL18的产生。从机制上讲，胆碱摄取减少会改变线粒体脂质分布，减弱线粒体ATP合成，并激活能量传感器AMP激活蛋白激酶（AMPK）。通过增强线粒体对DRP1的募集，AMPK刺激有丝分裂，有助于终止NLRP3炎症激活。相应地，胆碱激酶抑制剂改善了IL1β依赖性的急性和慢性炎症模型。

据悉，胆碱是一种维生素样营养物质，通过特定的转运体被摄取，并由胆碱激酶代谢，胆碱激酶将其转化为合成新的磷脂酰胆碱(PC)所需的磷酸胆碱，而磷脂酰胆碱是细胞膜的主要磷脂之一。

附：英文原文

Title: Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production

Author: Elsa Sanchez-Lopez, Zhenyu Zhong, Alexandra Stubelius, Stefano Tiziani, Monica Guma, Michael Karin

Issue&Volume: Jun 04, 2019 Volume 29Issue 6

Abstract: Choline is a vitamin-like nutrient that is taken up via specific transporters and metabolized by choline kinase, which converts it to phosphocholine needed for de novo synthesis of phosphatidylcholine (PC), the main phospholipid of cellular membranes. We found that Toll-like receptor (TLR) activation enhances choline uptake by macrophages and microglia through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline phosphorylation attenuated NLRP3 inflammasome activation and IL-1β and IL-18 production in stimulated macrophages. Mechanistically, reduced choline uptake altered mitochondrial lipid profile, attenuated mitochondrial ATP synthesis, and activated the energy sensor AMP-activated protein kinase (AMPK). By potentiating mitochondrial recruitment of DRP1, AMPK stimulates mitophagy, which contributes to termination of NLRP3 inflammasome activation. Correspondingly, choline kinase inhibitors ameliorated acute and chronic models of IL-1β-dependent inflammation.

DOI: https://doi.org/10.1016/j.cmet.2019.03.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30139-1