Effects of ketone body supplementation on cardiac remodeling induced by the sepsis model in rats

Abstract

Sepsis is organ dysfunction caused by a dysregulated host response to infection. In septic shock, sepsis is associated with worsening circulatory, cellular, and metabolic dysfunction that dramatically increases the risk of death. The effects of septic shock on the cardiovascular system are well studied in the literature, and the resulting cardiac dysfunction is termed septic cardiomyopathy. Several pathways are involved in sepsis-induced myocardial injury, including production of reactive oxygen species (ROS), mitochondrial dysfunction, alteration of microRNAs (miRNAs) expression, alterations in the intestinal microbiota, metabolic profile, and energy metabolism. The cardiac changes resulting from these events are called cardiac remodeling. Among the other substrates for energy production by the myocardium, ketone bodies provide an additional source of fuel for the myocardium when fatty acids and glucose cannot fully meet energy needs, as occurs in cardiac remodeling. In this scenario, supplementing ketone bodies may represent a promising strategy, with ²-hydroxybutyrate (²-OHB) being the most abundant and studied ketone body. Therefore, this study aims to investigate the effect of ketone body supplementation on cardiac remodeling and mortality in the ligature and cecal puncture-induced sepsis model in rats. Male Wistar rats will be submitted to the sepsis induction model and then divided into 4 groups: Sham control (n=25), Sham with supplementation of ketone bodies (n=25), Sepsis control (n=25), and Sepsis with supplementation of ketone bodies (n=25). Euthanasia will be performed after seven days, followed by morphological, functional, and biochemical exams. More specifically, miRNA expression, metabolic profile, oxidative stress, and intestinal microbiota will be evaluated. Values are expressed as mean ± standard deviation and comparisons are performed using the two-way ANOVA test with a significance level of 5%.