Effect of carnosic acid on olanzapine induced weight gain and metabolic abnormalities in rat

Introduction: Studies have shown that taking some antipsychtic drugs such as olanzapine is associated with weight gain and metabolic disorders in patients. Rosemary is widely used because of its antioxidant effects. Carnosic acid is the main part of commercial extract of rosemary. It has been shown that carnosic acid possesses antiobesity and lipid lowering effects. In this study, the effect of carnosic acid on obesity and metabolic disorders induced by olanzapine has been evaluated in rats. Materials & Methods: Rats were divided into six groups. Control (olanzapine solvent and carnosic acid solvent), Olanzapine (5mg/kg/day, IP.), Carnosic acid (5, 10, 20 mg/kg/day, oral) plus olanzapine (5 mg/kg/day, IP.), and carnosic acid (20 mg/kg/day, oral). Treatments were continued for 15 days. Body weight changes and food intake were measured during the experiment. Systolic blood pressure, glucose, triglyceride, total cholesterol, HDL cholesterol and plasma leptin levels were evaluated at the end of the study. The effects of olanzapine on the expression of AMPKα, p-AMPK, p-ACC were evaluated in liver by western blot method. Results: The present study showed that olanzapine 5 mg/kg for 15 days caused a significant increase in weight (P <0.001) and food intake (P <0.01) compared to control. Significant increase in serum level of triglyceride (P <0.001), fasting blood glucose (P <0.05), leptin secretion (P <0.01), and systolic blood pressure (P <0.05) were observed at the end of study. Administration of 20 mg/kg of carnosic acid resulted in a significant reduction in the weight and metabolic factors as compared to the olanzapine group receiving 5mg/kg. Also, the expression of AMPK and p-ACC in the liver tissue of olanzapine group, 5mg/kg, significantly decreased (P <0.01) compared to the control group. On the other hand, 20 mg/kg dose of carnosic acid increased the AMPK protein (P <0.05) and p-ACC (P <0.001). Conclusion: Olanzapine increases the amount of leptin secretion that increases nutritional intake and weight gain, which can disrupt the normal metabolic status of the body. On the other hand, the administration of carnosic acid with olanzapine inhibited the increase of leptin level following olanzapine, which resulted in lower food intake and decreased weight and metabolic factors.

کلیدواژه ها:

carnosic acid ، olanzapine ، obesity ، antipsychotic ، AMPK