The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns and Coronary Artery Disease Risk. Issue 4 (11th April 2018)

• Record Type: Journal Article
• Authors: Matthan, Nirupa R; Solano-Aguilar, Gloria; Meng, Huicui; Lamon-Fava, Stefania; Goldbaum, Audrey; Walker, Maura E; Jang, Saebyeol; Lakshman, Sukla; Molokin, Aleksey; Xie, Yue; Beshah, Ethiopia; Stanley, James; Urban Jr., Joseph F; Lichtenstein, Alice H
• Is Part Of: Journal of nutrition. Volume 148:Issue 4(2018)
• Page Start: 542
• Page End: 551
• Publication Date: 2018-04-11
• Subjects: Ossabaw pig -- dietary patterns -- atherosclerosis -- cardiometabolic risk factors -- atorvastatin -- coronary histopathology; Nutrition -- Periodicals; Diet -- Periodicals; 613.205
• DOI: 10.1093/jn/nxy002
• Languages: English
• ISSNs: 0022-3166

Abstract

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.