Kidney plays an important role in ketogenesis induced by risperidone and voluntary exercise in juvenile female rats

The positive role of ketone bodies in the treatment for mental disorders has been demonstrated. Ketogenesis can be triggered by not only exercise and diet but also metabolic disorders. This study aimed to explore the role of risperidone and exercise in ketogenesis. Thirty-two juvenile female Sprague Dawley rats were randomly assigned into four groups: Vehicle-Sedentary, Risperidone (0.9 mg/kg; b.i.d)-Sedentary, Vehicle-Exercise (three hours daily access to running wheels) and Risperidone-Exercise groups for four weeks. Exercise-intervention significantly ameliorated the risperidone-induced increase in white adipose mass, fasting plasma triglyceride and insulin levels. Compared to the vehicle-exercise group, the risperidone-exercise group had significantly higher plasma β-hydroxybutyrate (β-HB) level, which had a positive correlation with plasma non-esterified fatty acid levels. Risperidone-treatment upregulated expression of ketogenic key enzyme, mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (HMGCS2) in the kidney rather than liver. Exercise-intervention significantly enhanced renal carnitine palmitoyltransferase1A (CPT1A) expression. These results suggested that the kidney plays an important role in ketogenesis associated with risperidone and exercise. Therefore, it is important to monitor the levels of plasma ketone bodies while exercise intervention is utilized to prevent risperidone-induced metabolic disorders in young people.