The Ossabaw pig is a suitable translational model to evaluate dietary patterns and coronary artery disease risk

Authors: MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Solano-Aguilar, Gloria; MENG, HUICUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GOLDBAUM, AUDREY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WALKER, MAURA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Jang, Saebyeol; Lakshman, Sukla; Molokin, Aleksey; XIE, YUE - Sichuan Agricultural University; Beshah, Ethiopia; STANLEY, JAMES - Alizée Pathology; Urban, Joseph; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/26/2017
Publication Date: 4/11/2018
Citation: Matthan, N.R., Solano Aguilar, G., Meng, H., Lamon-Fava, S., Goldbaum, A., Walker, M.E., Jang, S., Lakshman, S., Molokin, A., Xie, Y., Beshah, E., Stanley, J., Urban Jr, J.F., Lichtenstein, A.H. 2018. The Ossabaw pig is a suitable translational model to evaluate dietary patterns and coronary artery disease risk. Journal of Nutrition. 148(4):542-552. https://doi.org/10.1093/jn/nxy002.
DOI: https://doi.org/10.1093/jn/nxy002

Interpretive Summary: The Ossabaw miniature pig has been established as a model for metabolic syndrome, non-alcoholic fatty liver, and coronary artery disease (CAD) when fed a diet high in trans fatty acids and fructose in caloric excess. However, lacking is a comprehensive assessment of the response of this animal model to diets designed to mimic those typically consumed by humans. Thus, the study objective was to adjudicate the Ossabaw pig as a CAD model to study dietary patterns and drug interactions. Specifically, we evaluated the effect of a Western Diet (WD, high in saturated fat, cholesterol, refined grains) and Heart Healthy Diet (HHD, high in unsaturated fat, whole grain, fruits/vegetables), with/without atorvastatin (Statin) therapy, on cardiometabolic risk factors and atherosclerosis development. Thirty-two pigs were randomly assigned to 4 groups: WD, WD+Statin, HHD and HHD+Statin and fed the respective diets for 8 months, with statin provided during the last 6 months. Results indicate that pigs fed the Western diet manifested dyslipidemia and chronic inflammation that was accompanied by early stages of atherosclerosis development compared to pigs fed the heart health diet, with or without statins. This unfavorable risk profile was modestly improved in the Western diet-fed pigs that were on statins. This presents a new experimental model of CAD in which to further study various dietary patterns and to elucidate potential mechanistic pathways.

Technical Abstract: Background-The Ossabaw pig is an established model for obesity related metabolic disorders when fed extreme diets in caloric excess. To increase the translational nature of this model, we evaluated the effect of isocaloric diets resembling two human dietary patterns: Western Diet (WD, high in saturated fat, cholesterol, refined grains) and Heart Healthy Diet (HHD, high in unsaturated fat, whole grain, fruits/vegetables), with/without atorvastatin (S) therapy, on cardiometabolic risk factors and atherosclerosis development. Methods and Results-Thirty-two pigs were randomly assigned to 4 groups: WD, WD+S, HHD and HHD+S and fed the respective diets for 8 months, with S provided during the last 6 months. Body composition, cardiometabolic risk profile and coronary histopathology were assessed using standard methodology. Pigs in the HHD groups had significantly lower LDL-C, nHDL-C and alkaline phosphatase (HHD and HHD+S vs. WD and WD+S), as well as hsCRP (HHD vs. WD), HDL-C (HHD+S vs. WD and WD+S) and TG (HHD+S vs. WD) levels. Histopathological evaluation documented less atheromatous change/lesion incidence in the coronary arteries, and lower aortic lipid deposition in HHD and HHD+S vs. WD fed pigs. Modest improvements in cardiometabolic risk factors and lower degree of lesion formation was observed in WD+S vs. WD fed pigs. Conclusions-Ossabaw pigs manifested a dyslipidemic profile accompanied by early stage atherosclerosis when fed a WD compared to a HHD and HHD+S, which was moderately attenuated in the WD+S group. This phenotype presents a new translational model to examine mechanistic pathways of food based dietary patterns on atherosclerosis development.