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: Huqun Li, Maosheng Fang, Mingzhen Xu, Shihong Li, Juan Du, Weiyong Li, Hui Chen
• Journal: PloS one (PLoS One) Vol. 11 Issue 12 Pg. e0167930 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27973621 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Blood Glucose
• Fatty Acids
• Insulin
• Benzodiazepines
• Palmitic Acid
• Fatty Acid Desaturases
• 8,11,14-Eicosatrienoic Acid
• Olanzapine

Topics

• 8,11,14-Eicosatrienoic Acid (blood)
• Animals
• Antipsychotic Agents (adverse effects)
• Area Under Curve
• Benzodiazepines (adverse effects)
• Blood Glucose (analysis)
• Chronic Disease
• Fatty Acid Desaturases (metabolism)
• Fatty Acids (blood)
• Female
• Glucose Tolerance Test
• Insulin (blood)
• Insulin Resistance
• Mice
• Mice, Inbred BALB C
• Olanzapine
• Palmitic Acid (blood)
• Random Allocation