Effect of different obesogenic diets on pancreatic histology in Ossabaw miniature swine

Obesity paired with hypertension, insulin resistance, and dyslipidemia—the metabolic syndrome—is a growing epidemic and is linked closely with other chronic diseases. In humans, obesity is a risk factor for fat accumulation in the pancreas and is a predictor of the severity of acute pancreatitis,1,2 and small animal models have confirmed these findings. For example, leptin-deficient obese mice were found to have significantly more total pancreatic fat, a condition termed nonalcoholic fatty pancreas disease (NAFPD).3 In another study, the severity of chemical-induced acute pancreatitis was greater in obese mice as compared to lean control mice.4 Ossabaw miniature swine are an excellent large animal model for investigating metabolic syndrome and associated conditions.5 These swine exhibit a thrifty genotype that allows for the storage of large amounts of fat for survival during famine.6 When fed with high-calorie and high-fat atherogenic diets, swine develop several characteristics of metabolic syndrome, including dyslipidemia, obesity, hypertension, and insulin resistance.7 Recently, we reported that feeding swine with a modified atherogenic/nonalcoholic steatohepatitis (NASH) diet consisting of cholesterol and fat calories from hydrogenated soybean oil, coconut oil, and lard induced abnormalities in liver histology that closely resemble those observed in human NASH.8 Because of the tendency of Ossabaw swine to develop obesity and metabolic syndrome, in this study, we evaluated whether swine also exhibited NAFPD and/or nonalcoholic steatopancreatitis (NASP) when fed with high-fructose, atherogenic, or modified atherogenic (NASH) diets.