2. Academic Validation
  3. Exogenous acetate attenuates inflammatory responses through HIF-1α-dependent glycolysis regulation in macrophage

Exogenous acetate attenuates inflammatory responses through HIF-1α-dependent glycolysis regulation in macrophage

  • Cell Mol Life Sci. 2024 Dec 27;82(1):21. doi: 10.1007/s00018-024-05521-8.
Na Li # 1,  Yi Gong # 2 3,  Yalin Zhu # 1 4,  Bo Li # 1,  Changli Wang 1,  Zhefan Wang 5,  Jun Wang 1,  Jie Huang 1,  Jinjun Bian 6,  Yan Zhang 7
Affiliations

Affiliations

  • 1 Faculty of Anesthesiology, Changhai Hospital (First Affiliated Hospital of Naval Medical University), Naval Medical University, Shanghai, 200433, China.
  • 2 Department of Respiratory Diseases and Critical Medicine, Quzhou Hospital Affiliated to Wenzhou Medical University, Quzhou, Zhejiang, 324000, China.
  • 3 Department of Respiratory Diseases and Critical Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China.
  • 4 Department of Anesthesiology, Naval Hospital of Eastern Theater, Zhoushan, China.
  • 5 Senior High School of Yangpu District, Shanghai, 200433, China.
  • 6 Faculty of Anesthesiology, Changhai Hospital (First Affiliated Hospital of Naval Medical University), Naval Medical University, Shanghai, 200433, China. jinjunbian@smmu.edu.cn.
  • 7 Faculty of Anesthesiology, Changhai Hospital (First Affiliated Hospital of Naval Medical University), Naval Medical University, Shanghai, 200433, China. Zhangyansmmu@163.com.
  • # Contributed equally.
PMID: 39725781 DOI: 10.1007/s00018-024-05521-8
Abstract

Cytokine storm is a hallmark for acute systemic inflammatory disease like sepsis. Intrinsic microbiome-derived short-chain fatty acid (SCFAs) like acetate modulates immune cell function and metabolism has been well studied. However, it remains poorly investigated about the effects and the underlying mechanism of exogenous acetate in acute inflammation like sepsis. Here, we observed that serum acetate accumulates in patients undergoing abdominal gastrointestinal surgery and in septic mice. Short exposure to high-dose exogenous acetate protects mice from sepsis by inhibiting glycolysis in macrophages, both in vivo and in vitro. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) stabilization or overexpression reverses the decreased glycolysis and pro-inflammatory cytokine production in macrophages and abrogates acetate's protective effect in septic mice. Meanwhile, we also found acetyl-CoA synthetase-2, but not GPR41 or GPR43, plays a key role in acetate's immunosuppressive effect. Acetate transiently increases acetyl-coenzyme A production, promoting histone acetylation and decreasing acetyl-transfer to NF-κB p65. These findings suggest that short exposure to mM-level acetate inhibits macrophage immune response linked to HIF-1α-dependent glycolysis. Taken together, we demonstrate short-term exposure of exogenous acetate could regulate inflammatory responses through attenuating HIF-1α-dependent glycolysis.

Keywords

Acetate; Glycolysis; HIF-1alpha; Inflammation; Macrophage.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z