Presentation description

Obesity and diabetes lead to increased fat and lipids (lipotoxicity) which can alter cardiac electrophysiology and increase the risk of ventricular arrhythmias and sudden cardiac death. Due to the increasing prevalence of both obesity and diabetes and the lack of therapies, it is important to have a better understanding of the underlying cellular pathways. Previous studies have shown that Leukotriene B4 (LTB4), a key lipid mediator involved in inflammation, is highly elevated in diabetic patients, and our lab has shown that its increased expression contributes to ventricular arrhythmogenesis in guinea pigs. This links the LTB4 pathway and cardiac disease due to metabolic disorders. Little is known about the role of the LTB4 pathway on cardiomyocytes, therefore our research focused on analyzing the expression of LTB4 pathway genes from ventricular heart tissue of guinea pigs fed either a high-fat or low-fat diet. We first used reverse transcription and real-time PCR to find the most appropriate reference genes for the project, and then conducted relative quantification on four genes in the LTB4 signaling pathway. We found that two genes were significantly downregulated in high-fat diet guinea pigs, while one was significantly upregulated. Our results may further clarify the role of LTB4 in ventricular arrhythmogenesis due to obesity and diabetes, which could lead to continued improvements in management options, and the development of new therapies for prevention of sudden cardiac death in patients with metabolic disorders.