Dataset Information

A Western-Type Dietary Pattern Induces an Atherogenic Gene Expression Profile in the Coronary Arteries of the Ossabaw Pig.

ABSTRACT:

Background

Current cardiovascular risk reduction guidance focuses on shifts in dietary patterns, rather than single foods or nutrients. Experimental studies are needed to identify the mechanisms by which food-based diets affect the development and progression of atherosclerosis.

Objectives

The aim of this study was to investigate the effect of 2 food-based dietary patterns and statin therapy on the transcriptome of the left anterior descending coronary artery of the Ossabaw pig.

Methods

Pigs were randomly assigned to 1 of 4 groups and fed isocaloric diets for 6 mo; Heart Healthy-style diet (HHD) (high in unsaturated fat, unrefined grain, fruits/vegetables) or Western-style diet (WD) (high in saturated fat, cholesterol, refined grain), with or without atorvastatin. A 2-factor edge R analysis was used to determine differential gene expression in the left anterior descending coronary artery.

Results

Relative to the HHD, the WD resulted in the differential expression of 143 genes, of which 139 genes were upregulated and 4 genes were downregulated (all log fold change ≥0.6, false discovery rate <0.10). The WD, compared with the HHD, resulted in the statistically significant upregulation of 8 atherosclerosis-associated pathways implicated in immune and inflammatory processes. There were no genes with significant differential expression attributable to statin therapy.

Conclusions

These data suggest that a WD induces alterations in the transcriptome of the coronary artery consistent with an inflammatory atherogenic phenotype in the Ossabaw pig with no significant modification by concurrent statin therapy.

SUBMITTER: Walker ME

PROVIDER: S-EPMC6488722 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

A Western-Type Dietary Pattern Induces an Atherogenic Gene Expression Profile in the Coronary Arteries of the Ossabaw Pig.

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

Current developments in nutrition 20190330 5

<h4>Background</h4>Current cardiovascular risk reduction guidance focuses on shifts in dietary patterns, rather than single foods or nutrients. Experimental studies are needed to identify the mechanisms by which food-based diets affect the development and progression of atherosclerosis.<h4>Objectives</h4>The aim of this study was to investigate the effect of 2 food-based dietary patterns and statin therapy on the transcriptome of the left anterior descending coronary artery of the Ossabaw pig.<h ...[more]

PMID: 31049488

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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.

Dataset Information

A Western-Type Dietary Pattern Induces an Atherogenic Gene Expression Profile in the Coronary Arteries of the Ossabaw Pig.

Background

Objectives

Methods

Results

Conclusions

Publications

A Western-Type Dietary Pattern Induces an Atherogenic Gene Expression Profile in the Coronary Arteries of the Ossabaw Pig.

Similar Datasets

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