Mechanism of Intermittent Fasting in Improving Olanzapine-induced Metabolic Disorders in Mice
10.12300/j.issn.1674-5817.2022.089
- VernacularTitle:间歇禁食法在改善奥氮平诱导小鼠代谢紊乱中的机制研究
- Author:
Han LI
1
;
Xiaorui ZHANG
2
;
Chengfang ZHANG
3
Author Information
1. Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 201108, China
2. Animal Core Facility of Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
3. Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
- Publication Type:Journal Article
- Keywords:
Intermittent fasting therapy;
Obesity;
Oxidative stress;
Mitochondria;
C57BL/6J mice
- From:
Laboratory Animal and Comparative Medicine
2023;43(1):3-10
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the beneficial role and potential mechanism of intermittent fasting in olanzapine-induced metabolic disorders. MethodsC57BL/6J mice were randomly divided into four groups: Saline + ad libitum (Saline+Ad libitum), Saline + intermittent fasting (Saline +IF), olanzapine administration + ad libitum (Olanzapine+ Ad libitum), and olanzapine administration + intermittent fasting (Olanzapine+IF)， with eight mice in each group. The IF group adopted the 5∶2 scheme, that is, fasting on Monday and Thursday every week, and eating freely in the rest of the time. Ad libitum feeding as the control of intermittent fasting, Saline gavage as the control of olanzapine administration. The experiment lasted for 12 weeks. The differences of body mass, liver mass and epididymal adipose tissue mass were compared between the olanzapine-treated group and the control group after IF intervention. The body fat mass, lean body mass, and visceral fat infiltration of mice were analyzed by nuclear magnetic resonance and HE staining, respectively. Furthermore, the levels of fasting blood glucose, insulin, and insulin resistance index (HOMA-IR) in the process of glucose metabolism were also measured by glucose oxidase method and radioimmunoassay, respectively. The effects of IF on H2O2 release and the level of cytochrome C mRNA, a marker related to mitochondrial damage, were detected by ELISA and real-time fluorescence quantitative PCR. ResultsAfter 12 weeks of treatment, olanzapine induced a significant increase in body mass, body fat, lean body mass and visceral fat infiltration (P<0.05), as well as fasting blood glucose, insulin, and HOMA-IR (P<0.05); however, IF significantly reduced the above indicators (P<0.05). Further studies showed that the release of H2O2 and the expression of Cytochrome C mRNA in adipose tissue of mice after intermittent fasting treatment were significantly decreased (P<0.05). ConclusionIntermittent fasting therapy can alleviate olanzapine-induced metabolic disorders in mice. The underlying mechanism may involve the inhibition of oxidative stress level and the maintenance of mitochondrial functions.
