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.