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STING协调多不饱和脂肪酸代谢和炎症反应之间的相互作用
作者:小柯机器人 发布时间:2022/1/5 14:47:18

法国蒙彼利埃大学Nadine Laguette、Isabelle K. Vila等研究人员合作发现,STING协调多不饱和脂肪酸代谢和炎症反应之间的相互作用。该研究于2022年1月4日发表于国际一流学术期刊《细胞—代谢》。

研究人员揭示了核酸依赖性炎症反应和代谢平衡的协调。研究人员发现,STING(干扰素基因的刺激因子)蛋白通过抑制脂肪酸去饱和酶2(FADS2)在多不饱和脂肪酸(PUFA)去饱和中的限速酶来调节代谢平衡。STING敲除和激动剂介导的降解增加了与FADS2相关去饱和酶的活性,并导致了驱动产热的PUFA衍生物积累。STING激动剂直接激活了FADS2依赖性的去饱和,促进了代谢的改变。PUFA反过来抑制了STING,从而调节了抗病毒反应,有助于解决STING相关的炎症。

因此,研究人员揭示了STING和FADS2之间的负向调节反馈回路,这能够对炎症反应进行微调。这些结果强调了代谢改变在与STING异常激活和STING靶向治疗相关人类病症中的作用。

据悉,免疫和代谢平衡的协同改变是几种与炎症有关的病症的基础,从代谢综合症到传染病。

附:英文原文

Title: STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses

Author: Isabelle K. Vila, Hanane Chamma, Alizée Steer, Mathilde Saccas, Clara Taffoni, Evgenia Turtoi, Line S. Reinert, Saqib Hussain, Johanna Marines, Lei Jin, Xavier Bonnefont, Mathieu Hubert, Olivier Schwartz, Soren R. Paludan, Gaetan Van Simaeys, Gilles Doumont, Bijan Sobhian, Dimitrios Vlachakis, Andrei Turtoi, Nadine Laguette

Issue&Volume: 2022/01/04

Abstract: Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the STING (stimulator of interferon genes) protein regulates metabolic homeostasis through inhibition of the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in polyunsaturated fatty acid (PUFA) desaturation. STING ablation and agonist-mediated degradation increased FADS2-associated desaturase activity and led to accumulation of PUFA derivatives that drive thermogenesis. STING agonists directly activated FADS2-dependent desaturation, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolving STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING-targeting therapies.

DOI: 10.1016/j.cmet.2021.12.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00626-4

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx