Hesperidin Attenuate Olanzapine-Induced Weight Gain, Dysregulation of Lipid and Glucose Metabolism in Rats

Background: Olanzapine causes alterations in lipid and glucose metabolism, indicated by weight gain, and altered metabolic profiles. Hesperidin has been related to numerous positive health benefits including improvements in cardiovascular and metabolic function making it a potentially suitable candidate to counteract the negative effects of olanzapine treatment. Hence the purpose of the study is to investigate the effect of hesperidin on olanzapine-induced weight gain, and associated lipid and glucose metabolic dysfunctions in female Sprague Dawley rats. Materials and Methods: Olanzapine (2 mg/kg b.i.d. i.p.) was administered for 28 days to induce weight gain, dyslipidemia and insulin resistance in rats. Hesperidin was tested at doses of 50, 100, 200 mg/kg p.o. over 28 days. Body weight, food intake, and water intake were noted daily. Locomotor activity was recorded weekly. Novel object recognition test, Oral glucose tolerance test, and Homeostatic Model Assessment for Insulin Resistance and antioxidant biomarkers were measured followed by histopathological examination. Results and Discussion: Treatment with hesperidin notably reduced the weight gain and hyperphagia brought on by olanzapine administration. Significant improvement in locomotor activity was observed upon hesperidin administration. Further, hesperidin resulted in a significant improvement in the discrimination ratio in the Novel object recognition test. Administration of hesperidin significantly reduced the glucose intolerance, insulin resistance and dyslipidemia induced by olanzapine treatment. Furthermore, leptin and adiponectin levels were significantly improved upon hesperidin administration. Additionally, there was a significant improvement in anti -oxidant biomarkers followed by amelioration of histological examination. Conclusion: In conclusion, it was found that hesperidin reduced weight gain, and improved lipid, and glucose dysregulation caused by olanzapine administration. Additionally, it mitigates olanzapine-induced changes in plasma levels of leptin, and adiponectin. Hesperidin also improved cognitive behavior in olanzapine-treated rats.