Thermoneutral housing and preexisting obesity do not abolish the sexually dimorphic effects of olanzapine on weight gain in mice

Objective In contrast to what is seen clinically, male mice are resistant to antipsychotic‐induced obesity. This is problematic as preclinical studies examining mechanisms of antipsychotic‐induced metabolic dysfunction might be relevant to only half the population. This study sought to determine whe...

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Published in:Obesity (Silver Spring, Md.) Md.), 2023-02, Vol.31 (2), p.454-465
Main Authors: Seguin, Ian, Medak, Kyle D., Shamshoum, Hesham, Hahn, Margaret K., Wright, David C.
Format: Article
Language:English
Subjects:
Animals
Antipsychotic Agents - adverse effects
Antipsychotics
Benzodiazepines - adverse effects
Carbohydrates
Diet
Energy
Fatty acids
Female
Females
Glucose
Homeostasis
Housing
Liver
Male
Metabolism
Metabolites
Mice
Monitoring systems
Obesity
Obesity - metabolism
Olanzapine
Proteins
Psychotropic drugs
Schizophrenia
Temperature
Weight Gain
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Summary:Objective In contrast to what is seen clinically, male mice are resistant to antipsychotic‐induced obesity. This is problematic as preclinical studies examining mechanisms of antipsychotic‐induced metabolic dysfunction might be relevant to only half the population. This study sought to determine whether housing mice at thermoneutrality and under conditions of preexisting obesity, steps that have not been previously considered, would uncover a greater obesogenic effect of the antipsychotic olanzapine (OLZ). Methods C57BL6/J mice were fed a low‐ or high‐fat diet (HFD) for 4 weeks and then switched to a control HFD or an HFD supplemented with OLZ for 6 weeks. Results Irrespective of obesity, OLZ treatment attenuated weight gain and increased energy expenditure in male mice. In females, OLZ increased food intake and potentiated weight gain in mice with preexisting obesity. Conclusions Despite taking steps to increase clinical translatability, this study did not unmask an obesogenic effect of OLZ in male mice. Interestingly, prior studies in female mice could have been underestimating the metabolic consequences of OLZ by not considering the importance of preexisting obesity. Uncovering the mechanisms conferring resistance to weight gain in males may provide clues for approaches to counter the metabolic side effects of antipsychotics clinically.
ISSN:1930-7381
1930-739X
DOI:10.1002/oby.23630