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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.

SUBMITTER: Walker ME

PROVIDER: S-EPMC6935368 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Walker Maura E ME Matthan Nirupa R NR Solano-Aguilar Gloria G Jang Saebyeol S Lakshman Sukla S Molokin Aleksey A Faits Tyler T Urban Joseph F JF Johnson W Evan WE Lamon-Fava Stefania S Lichtenstein Alice H AH

The Journal of nutritional biochemistry 20190220

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 di ...[more]

PMID: 30981985

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Project description:BackgroundAnimal models that mimic diet-induced human pathogenesis of chronic diseases are of increasing importance in preclinical studies. The Ossabaw pig is an established model for obesity-related metabolic disorders when fed extreme diets in caloric excess.ObjectiveTo increase the translational nature of this model, we evaluated the effect of diets resembling 2 human dietary patterns, the Western diet (WD) and the Heart Healthy Diet (HHD), without or with atorvastatin (-S or +S) therapy, on cardiometabolic risk factors and atherosclerosis development.MethodsOssabaw pigs (n = 32; 16 boars and 16 gilts, aged 5-8 wk) were randomized according to a 2 × 2 factorial design into 4 groups (WD-S, WD+S, HHD-S, and HHD+S) and were fed the respective diets for 6 mo. The WD (high in saturated fat, cholesterol, and refined grain) and the HHD (high in unsaturated fat, whole grain, and fruit and vegetables) were isocaloric [38% of energy (%E) from fat, 47%E from carbohydrate, and 15%E from protein]. Body composition was determined by using dual-energy X-ray absorptiometry, serum fatty acid (FA) profiles by gas chromatography, cardiometabolic risk profile by standard procedures, and degree of atherosclerosis by histopathology.ResultsSerum FA profiles reflected the predominant dietary FA. Pigs fed the WD had 1- to 4-fold higher concentrations of LDL cholesterol, non-HDL cholesterol, HDL cholesterol, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor α (TNF-α), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) compared with HHD-fed pigs (all P-diet < 0.05). Statin therapy significantly lowered concentrations of LDL cholesterol (-39%), non-HDL cholesterol (-38%), and triglycerides (-6%) (P-statin < 0.02). A greater degree of atheromatous changes (macrophage infiltration, foam cells, fatty streaks) and lesion incidence was documented in the coronary arteries (P-diet < 0.05), as well as 2- to 3-fold higher lipid deposition in the aortic arch or thoracic aorta of WD- compared with HHD-fed pigs (P-diet < 0.001).ConclusionsOssabaw pigs manifested a dyslipidemic and inflammatory profile accompanied by early-stage atherosclerosis when fed a WD compared with an HHD, which was moderately reduced by atorvastatin therapy. This phenotype presents a translational model to examine mechanistic pathways of whole food-based dietary patterns on atherosclerosis development.

Project description:Background & aimsDietary fiber is implicated as a risk factor for diverticulitis. Analyses of dietary patterns may provide information on risk beyond those of individual foods or nutrients. We examined whether major dietary patterns are associated with risk of incident diverticulitis.MethodsWe performed a prospective cohort study of 46,295 men who were free of diverticulitis and known diverticulosis in 1986 (baseline) using data from the Health Professionals Follow-Up Study. Each study participant completed a detailed medical and dietary questionnaire at baseline. We sent supplemental questionnaires to men reporting incident diverticulitis on biennial follow-up questionnaires. We assessed diet every 4 years using a validated food frequency questionnaire. Western (high in red meat, refined grains, and high-fat dairy) and prudent (high in fruits, vegetables, and whole grains) dietary patterns were identified using principal component analysis. Follow-up time accrued from the date of return of the baseline questionnaire in 1986 until a diagnosis of diverticulitis, diverticulosis or diverticular bleeding; death; or December 31, 2012. The primary end point was incident diverticulitis.ResultsDuring 894,468 person years of follow-up, we identified 1063 incident cases of diverticulitis. After adjustment for other risk factors, men in the highest quintile of Western dietary pattern score had a multivariate hazard ratio of 1.55 (95% CI, 1.20-1.99) for diverticulitis compared to men in the lowest quintile. High vs low prudent scores were associated with decreased risk of diverticulitis (multivariate hazard ratio, 0.74; 95% CI, 0.60-0.91). The association between dietary patterns and diverticulitis was predominantly attributable to intake of fiber and red meat.ConclusionsIn a prospective cohort study of 46,295 men, a Western dietary pattern was associated with increased risk of diverticulitis, and a prudent pattern was associated with decreased risk. These data can guide dietary interventions for the prevention of diverticulitis.

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

Publications

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

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