Evaluation of metabolic reprogramming and lipid droplet accumulation in the heart during experimental sepsis and its consequences on long-term cardiovascular changes

Sepsis is a life-threatening organ dysfunction resulting from a dysregulated immunometabolic response of the host to infection, and it is one of the leading causes of death in intensive care units. Survival in sepsis does not necessarily equate to the restoration of quality of life or improved outcomes for survivors. Cardiovascular changes are among the long-term manifestations, but the mechanisms involved are not yet fully understood. Evidence suggests that the systemic inflammatory response and metabolic changes contribute to cardiac dysfunction. Among the main metabolic changes observed in sepsis, dysregulation of lipid metabolism stands out, including increased accumulation of lipid droplets (LDs) in various tissues. LCs are important structures for cellular lipid and energy homeostasis. In this context, the role of dysregulation of lipid metabolism and LCs in the cardiac pathophysiology of sepsis still requires investigation. Our hypothesis is that metabolic reprogramming and the accumulation of LCs in the myocardium contribute to the cardiac changes observed during sepsis and its long-term consequences. The objective of this study is to characterize changes in lipid metabolism and the accumulation of CL in the cardiac pathophysiology of experimental sepsis. To this end, mice underwent cecal ligation and puncture (CLP) to induce experimental sepsis, and hearts were collected for analysis of lipid metabolism at 24 h, 48 h, and 15 days. Our data indicate that sepsis induces increased expression of genes associated with lipid metabolism at 48 h and 15 days. Furthermore, the sepsis-induced cardiac inflammatory response appears to be compartmentalized, with greater evidence in the atrium rather than in the entire heart. Taken together, the results indicate that lipid metabolism is reprogrammed in the hearts of animals subjected to sepsis, during both the acute and late phases of sepsis.