Pulmonary metabolic imbalances and mitochondrial ultrastructural remodeling in lipopolysaccharide-induced acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a critical disease of high mortality. Recent studies have confirmed that metabolic alterations and mitochondrial dysfunction is in involved in the progression of various pulmonary diseases. Moreover, significantly altered metabolite abundances are important in determining the severity of ARDS. Therefore, this study aims to illuminate the pulmonary metabolic profile, investigate the mitochondrial features of ARDS <i>via</i> the integration of metabolomic and transcriptomic analyses, elucidate the pathogenetic mechanism of ARDS. Metabolomic data from ARDS patients were downloaded and reanalyzed. Then Mice were randomly allocated into one of three groups as follows: the sham group; the LPS-2 day group (L2); and the LPS-4 day group (L4). All the mice in LPS group were anesthetized and received an intratracheal instillation of LPS. The sham group mice received only sterile saline. Pulmonary metabolic profiles were measured by integrating metabolomic analyses with transcriptomic analyses, and mitochondrial features in the mouse lungs were investigated <i>via</i> integrative -omics, mitochondrial ultrastructural detection and mitochondrial dynamics quantification. Inflamed lungs induce global metabolic perturbations that limit fatty acid oxidation, facilitate glucose consumption, accelerate amino acid metabolism and anaplerotic flux in the TCA cycle. In addition, impaired energetics followed by mitochondrial morphology alteration and mitochondrial dynamics imbalance are also validated in lung of ARDS. Global metabolic imbalance and substantial mitochondrial ultrastructural remodeling, characterized by a reduction in cristae density with significant activation of mitochondrial fission processes, have been verified to be pathogenic mechanisms in the lungs of ARDS patients.