Effect of high fat diet‐induced type 2 diabetes on liver and serum paraoxonase activities in C57BL/6J mice

Abstract

Diabetes mellitus is the seventh leading cause of death in the U.S. and is a major risk factor for cardiovascular disease. The causative link between type 2 diabetes, which accounts for 90–95% of all cases of diabetes mellitus, and increased prevalence of cardiovascular disease remains elusive. In recent years it has been discovered that the serum level and activity of paraoxonase‐1 (PON1), a cardioprotective enzyme, is decreased in humans with type 2 diabetes. Therefore, the current study explored the effect of high fat diet‐induced type 2 diabetes on PON1 production and activity in C57BL/6J mice. After twelve weeks, animals in the high fat fed group were obese, hyperinsulinemic, hyperglycemic, dyslipidemic, and hyperleptinemic when compared to low fat fed controls. Serum PON activity, as measured by hydrolysis of paraoxon, was significantly elevated in the high fat fed animals while liver PON activity was unchanged. Serum levels of PON1 and apolipoprotein A‐1 protein were comparable between the two groups. However, hepatic PON1 protein levels were decreased in the high fat fed animals. Thus, the current data demonstrate that high fat diet‐induced diabetes in the present murine model increases PON activity in the serum without a corresponding increase in protein production. The present work was supported by a preliminary data grant from the College of Veterinary Medicine Department of Basic Sciences.