The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns and Coronary Artery Disease Risk.

ABSTRACT:

Background

Animal 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.

Objective

To 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.

Methods

Ossabaw 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.

Results

Serum 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).

Conclusions

Ossabaw 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.

SUBMITTER: Matthan NR 

PROVIDER: S-EPMC6669954 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature