Metabolic and endocrinal effects of N-desmethyl-olanzapine in mice with obesity: Implication for olanzapine-associated metabolic changes.

Abstract

Clinical use of the antipsychotic drug olanzapine (OLA) is associated with metabolic side effects to variable degrees. N-desmethyl-olanzapine (DMO) is one major metabolite of OLA, but its potential involvement in the metabolic responses remains unclear. Here we examined whether DMO can directly impact the metabolic, endocrinal and inflammatory parameters under conditions of metabolic disturbance. DMO administration (2 mg/kg, i.g.) to high-fat diet induced obesity mice for 4 weeks induced a remarkable loss of body weight and fat mass. DMO improved insulin resistance and energy expenditure in mice, but had no significant effects on dyslipidemia or hepatic steatosis. Moreover, DMO induced morphological changes in the white adipose tissue, accompanied by reduced interleukin-1β (IL-1β) production and increased UCP1 expression. These findings demonstrate that DMO is devoid of the metabolic side effects commonly observed for OLA during obesity, which suggests that the N-desmethyl metabolism may function to regulate the metabolic responses to OLA.

• Authors: Xueli Zhang, Yi Zhao, Hua Shao, Xiao Zheng
• Journal: Psychoneuroendocrinology (Psychoneuroendocrinology) Vol. 108 Pg. 163-171 (10 2019) ISSN: 1873-3360 [Electronic] England
• PMID: 31302499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Blood Glucose
• Insulin
• Benzodiazepines
• Pirenzepine
• desmethylolanzapine
• Olanzapine

Topics

• Animals
• Benzodiazepines (adverse effects)
• Blood Glucose
• Body Weight (drug effects)
• Dyslipidemias
• Energy Metabolism (drug effects)
• Fatty Liver
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy, metabolism)
• Olanzapine (adverse effects)
• Pirenzepine (analogs & derivatives, metabolism, pharmacology)