2. Academic Validation
  3. FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury

FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jun 13;1870(7):167299. doi: 10.1016/j.bbadis.2024.167299.
Jiaqi Kang 1,  Jie Wu 2,  Qinjie Liu 3,  Haiyang Jiang 4,  Weizhen Li 5,  Yangguang Li 1,  Xuanheng Li 1,  Chujun Ni 6,  Lei Wu 7,  Mingda Liu 8,  Haiqing Liu 6,  Liting Deng 9,  Zexing Lin 4,  Xiuwen Wu 10,  Yun Zhao 11,  Jianan Ren 12
Affiliations

Affiliations

  • 1 Research Institute of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, PR China.
  • 2 Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, PR China; Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, PR China.
  • 3 Department of General Surgery, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, PR China.
  • 4 Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, PR China.
  • 5 Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, PR China.
  • 6 Surgical Research Laboratory, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, PR China.
  • 7 Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, PR China.
  • 8 The Core Laboratory, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, PR China.
  • 9 Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.
  • 10 Research Institute of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, PR China. Electronic address: wuxiuwen@nju.edu.cn.
  • 11 Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: zhaoyun0562019@163.com.
  • 12 Research Institute of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, PR China. Electronic address: jiananr@nju.edu.cn.
PMID: 38878833 DOI: 10.1016/j.bbadis.2024.167299
Abstract

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting Enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

Keywords

FASN; Macrophages; Malonyl-CoA; STING.

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