Classical Activation of Macrophages Leads to Lipid Droplet Formation Without de novo Fatty Acid Synthesis

被引:52
作者
Rosas-Ballina, Mauricio [1 ]
Guan, Xue Li [2 ]
Schmidt, Alexander [3 ]
Bumann, Dirk [1 ]
机构
[1] Univ Basel, Focal Area Infect Biol, Biozentrum, Basel, Switzerland
[2] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore
[3] Univ Basel, Prote Core Facil, Biozentrum, Basel, Switzerland
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
基金
瑞士国家科学基金会;
关键词
lipid metabolism; macrophage activation; lipid droplet (LD); beta-oxidation; interferon; inflammation; NITRIC-OXIDE; TRIGLYCERIDE ACCUMULATION; CELL RESPIRATION; S-NITROSYLATION; IN-VIVO; INHIBITION; METABOLISM; POLARIZATION; GAMMA; ATHEROSCLEROSIS;
D O I
10.3389/fimmu.2020.00131
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Altered lipid metabolism in macrophages is associated with various important inflammatory conditions. Although lipid metabolism is an important target for therapeutic intervention, the metabolic requirement involved in lipid accumulation during pro-inflammatory activation of macrophages remains incompletely characterized. We show here that macrophage activation with IFN gamma results in increased aerobic glycolysis, iNOS-dependent inhibition of respiration, and accumulation of triacylglycerol. Surprisingly, metabolite tracing with C-13-labeled glucose revealed that the glucose contributed to the glycerol groups in triacylglycerol (TAG), rather than to de novo synthesis of fatty acids. This is in stark contrast to the otherwise similar metabolism of cancer cells, and previous results obtained in activated macrophages and dendritic cells. Our results establish a novel metabolic pathway whereby glucose provides glycerol to the headgroup of TAG during classical macrophage activation.
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页数:12
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