Abstract
High fructose consumption is currently linked to metabolic disorders including insulin resistance and dyslipidemia as well as hepatic steatosis. Dimethyl dimethoxy biphenyl dicarboxylate (DDB) is a hepatoprotectant with antioxidant and anti-inflammatory properties. The aim of this study therefore is to evaluate the effect of DDB on high fructose-induced metabolic disturbances and hepatic steatosis in a rat model. Male Wistar rats were allocated into three groups: control, fructose-fed (10% in drinking water and 10% in diet), and fructose-fed DDB (300 mg/kg, orally)-treated groups. Rats were fed a high-fructose diet for 6 weeks, while DDB was administered for an additional 2 weeks. High-fructose consumption elevated serum glucose and insulin levels and impaired oral glucose tolerance test, revealing insulin resistance. It also increased serum triglycerides and alanine aminotransferase as well as visceral fat content and decreased serum high-density lipoprotein. Additionally, histopathological examination revealed that high fructose intake induced hepatic steatosis. These alterations were associated with increased serum uric acid as well as hepatic content of malondialdehyde and nitric oxide (NO) in addition to overexpression of inducible NO synthase (iNOS). DDB administration significantly ameliorated the high fructose-induced hepatic and metabolic alterations. In conclusion, DDB ameliorates high fructose-induced metabolic disorders and hepatic steatosis in rats. Such protection is, at least in part, due to the inhibition of lipid peroxidation, decrease in iNOS overexpression, and reduction of elevated uric acid.