Diesel Exhaust Particles Exposure Disrupts Cardiac Bioenergetics and Induces a Shift Towards Glycolytic Metabolism in Rats

Air pollution, particularly particulate matter (PM), is a major contributor to cardiovascular morbidity and mortality. We previously showed that diesel exhaust particles (DEPs) exposure increases arrhythmia susceptibility in rats, associated with myocardial oxidative stress and inflammation. However, the impact of DEPs on myocardial metabolism remains incompletely characterized. Here we aim to investigate whether DEP exposure induces time-dependent alterations in cardiac and plasma metabolic profiles following short- and longer-term intratracheal instillations in rats. Sprague–Dawley rats received intratracheal instillations of DEPs or saline three times weekly for one or three weeks. Myocardial and plasma metabolites were analyzed by 1H nuclear magnetic resonance spectroscopy, followed by discriminant and pathway analyses. Myocardial metabolomic profiling proved supportive of group separation, particularly one week after exposure. Seventeen of 22 metabolites were significantly altered. One week of DEP exposure reduced succinate, acetate, formate, 3-hydroxybutyrate, ATP, and ADP levels, a pattern consistent with alterations in mitochondrial oxidative metabolism and β-oxidation. Increased glucose and lactate levels were consistent with a greater reliance on glycolytic metabolism. Amino acid accumulation, along with increased inosine, pointed towards altered amino acid utilization and enhanced nucleotide degradation. Pathway analyses identified purine metabolism, glycolysis, citrate cycle, and pyruvate metabolism as some of the affected pathways, with enrichment of the citric acid cycle and mitochondrial electron transport chain. Most alterations resolved after three weeks. In contrast, changes in plasma were modest. In conclusion, DEP exposure induces transient metabolic remodeling in the myocardium, characterized by alterations consistent with reduced oxidative metabolism, increased glycolytic reliance, and disruption of energy and redox homeostasis, providing mechanistic insight into pollution-induced cardiac dysfunction.