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

Author
item WALKER, MAURA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Solano-Aguilar, Gloria
item Jang, Saebyeol
item Lakshman, Sukla
item Molokin, Aleksey
item FAITS, TYLER - Boston University
item Urban, Joseph
item JOHNSON, W - Boston University
item LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2019
Publication Date: 2/20/2019
Citation: Walker, M., Matthan, N., Solano Aguilar, G., Jang, S., Lakshman, S., Molokin, A., Faits, T., Urban Jr, J.F., Johnson, W.E., Lamon-Fava, S., Lichtenstein, A.H. 2019. A Western dietary pattern and atorvastatin induce epicardial adipose tissue interferon signaling in the Ossabaw pig. Journal of Nutritional Biochemistry. https://doi.org/10.1016/j.jnutbio.2019.02.003.
DOI: https://doi.org/10.1016/j.jnutbio.2019.02.003

Interpretive Summary: Epicardial adipose tissue, adipose tissue in contact with the coronary arteries, is an emerging risk factor for cardiovascular disease. It has yet to be determined if dietary patterns and statin medications may modulate epicardial adipose tissue gene expression. We found that a Western diet, relative to Heart Healthy diet, and statin therapy, relative to no statin, activated genes involved in immune signaling. Changes in gene expression by the Western diet and statin therapy were not associated with cardiovascular disease in the underlying artery.

Technical 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. A significant diet x statin interaction was found for 4 genes. Pathway analysis confirmed the up-regulation of interferon signaling in response to the WD and atorvastatin, and a potential diet x statin interaction indicating the effect of atorvastatin on interferon signaling is down-regulated with the WD relative to the HHD. An expression signature of 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.