Macrophage apoptosis contributes to acute lung injury (ALI). However, the relationship between cell metabolism and the apoptosis of macrophages remains unclear. In our study, murine alveolar macrophages (MH-S) were stimulated by lipopolysaccharide (LPS) to induce an apoptosis model; cell viability, mitochondrial membrane potential (MMP) and apoptosis rate were determined. TCA metabolites and fatty acids were measured; qPCR and western blot were used to detect gene and protein expressions. The LPS-induced ALI mice model was established, and pathological changes, inflammatory cytokines, and protein acetylation were evaluated. The results showed that LPS exposure impaired cell viability and increased apoptosis of alveolar macrophages (AM) in a concentration-dependent manner. LPS also downregulated the expression of the FAO rate-limiting enzyme carnitine palmitoyl transferase 1A (CPT1A), which was accompanied by suppression of fatty acid oxidation (FAO) and alterations of the fatty acid profile. CPT1A inhibitor etomoxir also promoted cell apoptosis of AM and decreased MMP. Overexpression of CPT1A ameliorated cell apoptosis of AM induced by LPS. Etomoxir and LPS decreased acetyl-CoA levels, and supplementation of acetyl-CoA prevented LPS-induced cell apoptosis. In addition, LPS led to the alteration of acetylated protein profiles. In vivo study, excessive cell apoptosis, decreased expression of proteins related to FAO, and decreased acetyl-CoA levels were detected in ALI animal models. Acetyl-CoA could relieve the apoptosis and inflammation in the lung induced by LPS. These findings suggested the essential role of CPT1A and acetyl-CoA in cell apoptosis of AM induced by LPS.
基金：
National Key Research and Development Project of China (grant number 2022YFA1304300), the NationalNatural Science Foundation of China (grant number 82200024, 82370025), the Shanghai Municipal Hospital Respiratory and Critical Care MedicineSpecialist Alliance, and the Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (grant number20dz2261100)
第一作者机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Pulm & Crit Care Med, Shanghai, Peoples R China[2]Shanghai Jiao Tong Univ, Inst Resp Dis, Sch Med, Shanghai, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Pulm & Crit Care Med, Shanghai, Peoples R China[2]Shanghai Jiao Tong Univ, Inst Resp Dis, Sch Med, Shanghai, Peoples R China
推荐引用方式(GB/T 7714)：
Shi Guochao,Wang Rong,Huang Chunrong.Augmenting Macrophages Apoptosis Induced by Carnitine Palmitoyl Transferase 1A Inhibition via Acetyl-CoA-Associated Protein Acetylation[J].IMMUNOLOGY.2025,doi:10.1111/imm.13917.
APA：
Shi, Guochao,Wang, Rong&Huang, Chunrong.(2025).Augmenting Macrophages Apoptosis Induced by Carnitine Palmitoyl Transferase 1A Inhibition via Acetyl-CoA-Associated Protein Acetylation.IMMUNOLOGY,,
MLA：
Shi, Guochao,et al."Augmenting Macrophages Apoptosis Induced by Carnitine Palmitoyl Transferase 1A Inhibition via Acetyl-CoA-Associated Protein Acetylation".IMMUNOLOGY .(2025)
