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Chronic Antipsychotic Treatment Increases Weight Gain and Energy Expenditure in Mice in a Sexually Dimorphic Manner

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Title: Chronic Antipsychotic Treatment Increases Weight Gain and Energy Expenditure in Mice in a Sexually Dimorphic Manner
Author: Seguin, Ian
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Wright, David
Abstract: Olanzapine (OLZ) is a second-generation antipsychotic that is used to treat schizophrenia and other mental health disorders. While effective at reducing psychoses, OLZ induces negative metabolic side effects including weight gain, dyslipidemia and impairments in glucose metabolism. While negative metabolic side effects of OLZ are reported clinically in both men and women, preclinical rodent models display sexual dimorphism with male mice being resistant to OLZ-induced weight gain. There are several limitations in the design of preclinical studies that could potentially be masking the effect of OLZ in male mice including housing temperature and using lean healthy mice. Therefore, the purpose of this thesis was to determine if housing mice under thermal neutral conditions and alongside pre-existing obesity would worsen the metabolic effects of OLZ. To test this hypothesis, we housed male and female C57BL6J at thermoneutrality (TN; 29oC) and fed them either a LFD or HFD for 4 weeks. Following this period, mice were then given a control HFD or HFD w/ OLZ (4 mg/kg/day) for 6 weeks. A clear sexual dimorphic response was seen with male mice displaying increases in energy expenditure and weight loss with OLZ treatment, whereas females were hyperphagic and gained weight, effects that were more pronounced in mice with pre-existing obesity. Collectively our results provide evidence of clear sex differences in the response to chronic OLZ treatment in mice housed at thermal neutrality.
URI: https://hdl.handle.net/10214/26967
Date: 2022-05
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