Abstract
Rationale
Second-generation antipsychotic (SGA) medications can produce abnormal weight gain and metabolic dysfunction in children, but little is known about the post-treatment consequences of adolescent SGA exposure.
Objectives
The objective of this study was to determine the long-term, post-treatment effects of adolescent olanzapine exposure on weight and metabolic function and whether dietary fish oil (FO) modulated any observed effects of olanzapine.
Methods
Male and female mice were fed a high-fat, high-sugar (HF-HS) diet or an HF-HS diet supplemented with fish oil (HF-HS-FO) and were treated with olanzapine or vehicle for 29 days beginning on postnatal day 37.
Results
In male mice, adolescent olanzapine treatment suppressed weight gain during and after treatment and improved metabolic function in adulthood; dietary fish oil reduced weight gain, increased expression of fatty acid oxidation genes, and decreased expression of genes associated with fatty acid synthesis and inflammation. In contrast, few effects were observed in female mice.
Conclusions
The current results suggest that adolescent olanzapine exposure can produce long-term alterations in weight and metabolic function in male mice and that dietary fish oil can reduce adverse effects of lifelong consumption of an HF-HS diet. Because expected adverse effects of adolescent olanzapine treatment were not observed, the potential beneficial effects of dietary fish oil for SGA-induced weight gain and metabolic dysfunction could not be evaluated.
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Acknowledgements
We want to thank Dr. Michael Young for guidance on conducting and interpreting the multilevel linear and non-linear models.
Funding
The current studies were supported by funding from the Obesity Research Cluster at Texas Tech University. The Obesity Research Cluster played no role in the design or conduct of the experiments.
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Soto, P.L., Ramalingam, L., George, B. et al. Long-term effects of adolescent exposure to olanzapine in C57BL/6 J mice and the impact of dietary fish oil supplementation. Psychopharmacology 239, 3117–3131 (2022). https://doi.org/10.1007/s00213-022-06193-7
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DOI: https://doi.org/10.1007/s00213-022-06193-7