[Animal Modeling] - Study on the Mechanism of Intermittent Fasting in Improving Metabolic Disorders Induced by Olanzapine in Mice

      Objective To investigate the protective effect and mechanism of intermittent fasting on metabolic disorders induced by olanzapine in mice.

  Methods C57BL/6J mice were randomly divided into four groups: saline+Ad libitum group, saline+intermittent fasting group, olanzapine+Ad libitum group, olanzapine+Ad libitum group, and olanzapine+intermittent fasting group, with 8 mice in each group. In the intermittent fasting group, a 5: 2 regimen was adopted, namely, fasting on Mondays and Thursdays of the week, and eating freely during the rest of the week, with intervention for 12 weeks; Free feeding was used as the control for intermittent fasting, and saline was used as the control for olanzapine administration. To compare the differences in body mass, liver mass, and epididymal adipose tissue mass between the olanzapine treated group and the control group after intermittent fasting intervention, and to analyze the changes in body fat, leptin, and visceral fat infiltration in mice using magnetic resonance and HE staining methods, respectively; At the same time, glucose oxidase assay and radioimmunoassay were used to determine the differences in fasting blood glucose, insulin, and insulin resistance index (HOMA-IR) levels during glucose metabolism in mice. ELISA and real-time fluorescence quantitative PCR were used to determine the content of H2O2 and the level of cytochrome C mRNA, a marker related to mitochondrial damage, respectively.

  Results After 12 weeks of treatment, olanzapine induced significant increases in body mass, body fat, leptin, and visceral fat infiltration in mice (P<0.05), as well as significant increases in fasting blood glucose, insulin, and insulin index (P<0.05); However, intermittent fasting can significantly reduce these indicators (P<0.05). Further research showed that the release of H2O2 and the expression of Cytochrome C mRNA in adipose tissue of mice after intermittent fasting treatment were significantly reduced (P<0.05).

  Conclusion Intermittent fasting can alleviate the metabolic disorder induced by olanzapine in mice, and its mechanism may be related to inhibiting the level of oxidative stress and maintaining mitochondrial function.