title: Chronic Olanzapine Treatment Induces Disorders of Plasma Fatty Acid Profile in Balb/c Mice: A Potential Mechanism for Olanzapine-Induced Insulin Resistance.
abstract: BACKGROUND
  Atypical antipsychotics such as olanzapine cause metabolic side effects leading to obesity and insulin resistance. The underlying mechanisms remain elusive. In this study we investigated the effects of chronic treatment of olanzapine on the fatty acid composition of plasma in mice.
  
  
  METHODS
  Twenty 8-week female Balb/c mice were randomly assigned to two groups: the OLA group and the control group. After treatment with olanzapine (10 mg/kg/day) or vehicle intraperitoneally for 8 weeks, fasting glucose, insulin levels and oral glucose tolerance test were determined. Effects on plasma fatty acid profile and plasma indices of D5 desaturase, D6 desaturase and SCD1 activity were also investigated.
  
  
  RESULTS
  Chronic administration of olanzapine significantly elevated fasting glucose and insulin levels, impaired glucose tolerance, but did not increase body weight. Total saturated fatty acids and n-6 polyunsaturated fatty acids were significantly increased and total monounsaturated fatty acids were significantly decreased, while total n-3 polyunsaturated fatty acids showed no prominent changes. Chronic olanzapine treatment significantly up-regulated D6 desaturase activity while down-regulating D5 desaturase activity. Palmitic acid (C16:0), dihomo-γ-linolenic acid (C20:3n-6) and D6 desaturase were associated with an increase probability of insulin resistance, whereas nervonic acid (C24:1) and SCD1 were significantly associated with a lower insulin resistance probability.
  
  
  CONCLUSIONS
  All results indicated that such drug-induced effects on fatty acid profile in plasma were relevant for the metabolic adverse effects associated with olanzapine and possibly other antipsychotics. Further studies are needed to investigate geneticand other mechanisms to explain how plasma fatty acids regulate glucose metabolism and affect the risk of insulin resistance.
authors.affiliation: Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Huqun
authors.initials: H
authors.lastname: Li
authors.affiliation: Wuhan Mental Health Center, Wuhan, PR China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000097:blood; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D001569:Benzodiazepines / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D002908:Chronic Disease; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D000077152:Olanzapine; D019308:Palmitic Acid / Q000097:blood; D011897:Random Allocation
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D001569:Benzodiazepines; D019308:Palmitic Acid; D044943:Fatty Acid Desaturases; D015126:8,11,14-Eicosatrienoic Acid; D000077152:Olanzapine