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Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK

文献类型：期刊论文

作者Peng, Chang8,9,10; Jiang, Haowen10; Jing, Liya1,10; Yang, Wenhua7,10; Guan, Xiaotong8,9; Wang, Hanlin10; Yu, Sike8,9; Cao, Yutang5,6; Wang, Min10; Ma, Huan8,10
刊名NATURE COMMUNICATIONS
出版日期2025-02-18
卷号16期号:1页码:20
DOI10.1038/s41467-025-57044-w
英文摘要Obesity is regarded as a chronic inflammatory disease involving adipose tissue macrophages (ATM), but whether immunometabolic reprogramming of ATM affects obesity remains unclarified. Here we show that in ATM glutaminolysis is the fundamental metabolic flux providing energy and substrate, bridging with AMP-activated protein kinase (AMPK) activity, succinate-induced interleukin-1 beta (IL-1 beta) production, and obesity. Abrogation of AMPK alpha in myeloid cells promotes proinflammatory ATM, impairs thermogenesis and energy expenditure, and aggravates obesity in mice fed with high-fat diet (HFD). Conversely, IL-1 beta neutralization or myeloid IL-1 beta abrogation prevents obesity caused by AMPK alpha deficiency. Mechanistically, ATP generated from glutaminolysis suppresses AMPK to decrease phosphorylation of the beta subunit of succinyl-CoA synthetase (SUCLA2), thereby resulting in the activation of succinyl-CoA synthetase and the overproduction of succinate and IL-1 beta; by contrast, siRNA-mediated SUCLA2 knockdown reduces obesity induced by HFD in mice. Lastly, phosphorylated SUCLA2 in ATM correlates negatively with obesity in humans. Our results thus implicate a glutaminolysis/AMPK/SUCLA2/IL-1 beta axis of inflammation and obesity regulation in ATM.
WOS关键词ADIPOSE-TISSUE ; SIRNA DELIVERY ; TCA CYCLE ; INFLAMMATION ; ACTIVATION ; POLARIZATION ; SUPPRESSES ; EXPRESSION ; IL-1-BETA ; INDUCTION
资助项目National Natural Science Foundation of China (National Science Foundation of China)[82273983] ; National Natural Science Foundation of China (National Science Foundation of China)[32000525] ; National Natural Science Foundation of China (National Science Foundation of China)[82130099] ; National Natural Science Foundation of China (National Science Foundation of China)[92253306] ; National Natural Science Foundation of China[2022YFA1303800] ; National Key R&D Program of China[23ZR1474700] ; Science and Technology Commission of Shanghai Municipality[22Y11908600] ; Medical Innovation Research Special Project of Shanghai ; Shanghai Institute of Materia Medica, Chinese Academy of Science[2022ZZ01013] ; Shanghai Institute of Materia Medica, Chinese Academy of Science[2023HIAS-Y030] ; Shanghai Institute of Materia Medica, Chinese Academy of Science[2023HIAS-V002] ; Shanghai Institute of Materia Medica, Chinese Academy of Science[2024HIAS-N001] ; Research Funds of Hangzhou Institute for Advanced Study, UCAS[YPM202101] ; Research Funds of Hangzhou Institute for Advanced Study, UCAS[YPGWM202401] ; Science and Technology Commission of Yangpu District[2024M760704] ; China Postdoctoral Science Foundation
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001425285400007
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/316317]  
专题新药研究国家重点实验室
通讯作者Jiang, Haowen; Tang, Erjiang; Li, Jia
作者单位1.Lingang Lab, Shanghai 201203, Peoples R China
2.Tongji Univ, Yangpu Hosp, Sch Med, Inst Gastrointestinal Surg & Translat Med, Shanghai 200090, Peoples R China
3.Tongji Univ, Yangpu Hosp, Sch Med, Ctr Clin Res & Translat Med, Shanghai 200090, Peoples R China
4.Fudan Univ, Coll Pharm, Shanghai 210023, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
8.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
9.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Peng, Chang,Jiang, Haowen,Jing, Liya,et al. Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK[J]. NATURE COMMUNICATIONS,2025,16(1):20.
APA Peng, Chang.,Jiang, Haowen.,Jing, Liya.,Yang, Wenhua.,Guan, Xiaotong.,...&Li, Jia.(2025).Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK.NATURE COMMUNICATIONS,16(1),20.
MLA Peng, Chang,et al."Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK".NATURE COMMUNICATIONS 16.1(2025):20.

入库方式： OAI收割

来源：上海药物研究所

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