Gender related differences in paraoxonase 1 response to high-fat diet-induced oxidative stress

Objective: To evaluate the influence of the pro-oxidant and proinflammatory state related to dietary obesity on serum paraoxonase 1 (PON1) activity in male and female rats. Methods and Procedures: Adult Wistar rats of both genders were fed on a high-fat diet to induce weight gain or standard diet for 14 weeks. Body weight was assessed weekly and food intake fortnightly throughout the dietary treatment. Biometrical parameters and serum lipid profile, glucose, insulin, and adipokine levels were measured. To assess the effect of dietary obesity on oxidative stress, levels of liver and serum thiobarbituric acid reactive substances, liver protein carbonyl groups, liver antioxidant enzymes activities, and serum PON1 activities were measured. Results: High-fat diet feeding induced a significant body weight gain in both male and female rats, as well as a reduction of liver antioxidant protection. High-fat diet increased serum lipid peroxides in male rats and reduced serum PON1 activities and serum apolipoprotein A-I (apoA-I) levels in females, although did not alter serum PON1 or apolipoprotein J (apoJ) levels. Discussion: Our results reveal a gender dimorphism in the high-fat diet-induced reduction of serum PON1 activity, which is likely to be related to the greater obese and proinflammatory state achieved in female rats. We suggest that the enhanced oxidative stress caused by dietary increased body weight, on leading to high-density lipoprotein (HDL), apoA-I or PON1 oxidation could entail the destabilization of the PON1 association to HDL or a direct inactivation of PON1 enzymatic activity, thus accounting for the decreased serum PON1 activities observed in female rats.