Increased cholesterol is vital to the development of coronary artery disease and type 2 diabetes in Ossabaw swine

Abstract

Ossabaw swine fed excess kcal high fat/cholesterol diet develop metabolic syndrome. Many studies have linked a high‐fructose diet to development of metabolic syndrome without dyslipidemia. We tested the hypothesis that a high fructose diet will induce metabolic syndrome (MetS) and a high fructose/fat/cholesterol diet will induce more severe, dyslipidemic MetS (DMetS). We fed healthy, lean Ossabaw swine control chow (N=9), high fructose diet (MetS; N=8), or high fructose/fat/cholesterol diet (DMetS; N=6) for 28 weeks. Compared to lean pigs, both MetS and DMetS developed obesity, glucose intolerance, hypertriglyceridemia, and hypertension. However, increased cholesterol was seen only in DMetS compared to lean, while MetS was not different from lean. Importantly, DMetS developed type 2 diabetes, as evidenced by significantly increased fasting blood glucose and pancreatic beta‐cell failure (lack of both hyperinsulinemic response to intravenous glucose tolerance test and beta‐cell immunohistochemistry). Intravascular ultrasound revealed very minimal CAD in lean and MetS, but CAD in DMetS was occlusive and diffuse. In conclusion, although several risk factors for CAD are present in MetS Ossabaw swine, dyslipidemia is a crucial component in the development of type 2 diabetes and CAD. The data are consistent with a role of lipotoxicity. Support: NIH RR013223, HL062552.