Thermally Oxidized Coconut Oil as Fat Source in High-Fat Diet Induces Hepatic Fibrosis in Diabetic Rat Model

In the present study, HFD/STZ-mediated type 2 diabetic rodent model was used to comparatively evaluate coconut oil (CO) and thermally oxidized CO (TCO) as fat sources for the development of NAFLD. Female Wistar rats (six in each group; average bwt 200 g) fed HFD containing either CO or TCO for 2 months along with an intraperitoneal injection of streptozotocin (30 mg/kg bwt) at the end of 1-month feeding were found to develop fatty liver and subsequent inflammatory changes when compared to the normal laboratory diet-fed animals over 2-month period. Dyslipidemia as well as enhanced activities of serum hepatic marker enzymes (e.g., AST, ALT, and ALP) were prominent in TCO-fed animals. Further, HFD-fed animals showed alterations in their hepatic redox equilibrium. Hepatic GSH and antioxidant enzyme activities that form the part of a protective mechanism against oxidative/carbonyl stress were found to be increased in HFD-fed rats. Supporting this, CO- and TCO-containing-HFD-fed animals had enhanced lipid peroxidation (increased TBARs). Thus, fatty liver with heightened antioxidant defense, lipid peroxidation, and inflammation indicate hepatosteatosis. Histological details of the hepatic tissues corroborated sufficiently with these observations and showed an increased incidence of macrovesicles, inflammation, and hepatocyte ballooning in the TCO-fed rats than in CO-fed animals. Further, in support of this proposition, hydroxyproline, an index of collagen formation, was found to be significantly increased in TCO-fed rats than in the CO-fed group. Overall, the study shows that the formulation of HFD incorporated with TCO as a fat source, combined with STZ injection, is an efficient dietary model for developing hepatosteatosis with fibrotic stage in rats within 2 months. Administration of this modified diet for a more extended period may be a good model for cirrhotic and hepatocellular carcinoma studies, which need to be further assessed.