A Western-type dietary pattern and atorvastatin induce epicardial adipose tissue interferon signaling in the Ossabaw pig

Abstract

Epicardial adipose tissue (EAT) inflammation is thought to potentiate the development of coronary artery disease (CAD). Overall diet quality and statin therapy are important modulators of inflammation and CAD progression. Our objective was to examine the effects and interaction of dietary patterns and statin therapy on EAT gene expression in the Ossabaw pig. Pigs were randomized to 1 of 4 groups; Heart Healthy diet (high in unsaturated fat, unrefined grain, fruits/vegetables [HHD]) or Western diet (high in saturated fat, cholesterol, refined grain [WD]), with or without atorvastatin. Diets were fed in isocaloric amounts for 6 months. A two-factor edge R analysis identified the differential expression of 21 genes. Relative to the HHD, the WD resulted in a significant 12-fold increase of radical s-adenosyl methionine domain containing 2 (RSAD2), a gene induced by interferon signaling. Atorvastatin led to the significant differential expression of 17 genes predominately involved in interferon signaling. Results were similar using the Porcine Translational Research Database. Pathway analysis confirmed the up-regulation of interferon signaling in response to the WD and atorvastatin independently. An expression signature of the largely interferon related differentially expressed genes had no predictive capability on a histological assessment of atherosclerosis in the underlying coronary artery. These results suggest that a WD and atorvastatin evoke an interferon mediated immune response in EAT of the Ossabaw pig, which is not associated with the presence of atherosclerosis.