The present study evaluated the protective effects of fenofibrate on liver function, oxidant–antioxidant balance, and insulin resistance (IR) in rats fed high‐fat–high‐fructose diet (HFFD). Twenty‐four male Sprague‐Dawley rats (110–130 gm) were allocated into four equal groups (n = 6). Rats in group I were fed a normal diet for 4 weeks. Rats in group II were fed a normal diet with fenofibrate at 50 mg/kg/day orally for four weeks. Rats in group III were fed a normal diet mixed with 25% palm oil and given 60% fructose solution orally for 4 weeks. Rats in group IV were fed a normal diet mixed with 25% palm oil, 60% oral fructose solution, and fenofibrate at 50 mg/kg/day orally for four weeks. After experimental induction, serum and liver tissue samples were collected to determine lipid profiles, glycemic status, antioxidant status, oxidative and stress markers, and histopathology of liver tissues. The results of the present study revealed that fenofibrate prevents the occurrence of fatty liver, enhancing glycemic status, decreasing oxidative stress, and improving antioxidant status. It can be concluded that fenofibrate has a lipotropic and antidiabetic role.
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