Risperidone upregulates the expression of adhesion molecules VCAM-I, and P-selectin in high-fat diet-induced obese mice

Abstract

Backgrounds: The prevalence of mental disorders has increased in the last decades. Risperidone is a second-generation antipsychotic drug used for major depressive disorder treatment. Our study aims to investigate the effects of risperidone on the expression of adhesion molecules involved in inflammation and other related complications in a pre-established obese mice model. Methods: Two obese treatment groups were administered 0.5 mg/kg and 1 mg/kg risperidone along with high fat. After 6 weeks of treatment, the food intake, body weights, abdominal-fat weights, liver weights, lipid profile (serum triglycerides, total cholesterol, high-density lipoprotein-cholesterol), and liver functions test (serum glutamic pyruvate transaminase, serum glutamate oxaloacetic transaminase, alkaline phosphatase) were evaluated. The relative gene expressions of PPAR-gamma, VCAM-1, P-selectin, and interleukin-6 (IL-6) were also compared. Results: The results showed a significant increase in food intake (p<0.001), body weight (p<0.01), abdominal-fat weight (p<0.01), liver weight (p<0.01), triglycerides (p<0.01), total cholesterol (p<0.05), serum glutamic pyruvate transaminase (p<0.05), serum glutamate oxaloacetic transaminase (p<0.001), alkaline phosphatase (p<0.05) and relative gene expression of PPARγ (p<0.01), VCAM-1 (p<0.05) for risperidone treated groups compared to the obese group. The relative gene expression of IL-6 for both doses was not increased as expected compared to the obese group. Limitations: The molecular pathways of the results were undiscovered. Conclusions: The study revealed that risperidone has an inducible action on fat deposition, liver dysfunction, cardiovascular diseases, and inflammation which may be effective in weight gain management intervention and the safety of risperidone treatment in obese patients. However, further molecular studies can explore the mechanisms behind these findings.

Keywords

• Risperidone
• Obesity
• Inflammation
• Lipid profile
• Gene expression
• Mice model