title: Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study.
abstract: BACKGROUND
  Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine.
  
  
  OBJECTIVE
  The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice.
  
  
  METHODS
  C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29.
  
  
  RESULTS
  Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 [0.16]; P < 0.05).
  
  
  CONCLUSIONS
  Clozapine 10 mg/kg was associated with significant decreases in body weight and significant increases in fasting blood glucose and glucose tolerance in these male C57BL/6 mice.
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Yuan
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Liang
authors.affiliation: Department of Pharmacy, Nanhua Hospital, Nanhua University, Hengyang, China.
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Huan-De
authors.initials: HD
authors.lastname: Li
keywords: blood glucose; body weight; clozapine; insulin resistance; mice; plasma lipid