Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice

<div><p>Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and “off-label” indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessi...

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Main Author: Mostafa M. Abbas (17058093) (author)
Other Authors: Paul Soto (18300805) (author), Latha Ramalingam (18300808) (author), Yasser El-Manzalawy (5659075) (author), Halima Bensmail (10400) (author), Naima Moustaid-Moussa (66960) (author)
Published: 2022
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_version_ 1864513519275212800
author Mostafa M. Abbas (17058093)
author2 Paul Soto (18300805)
Latha Ramalingam (18300808)
Yasser El-Manzalawy (5659075)
Halima Bensmail (10400)
Naima Moustaid-Moussa (66960)
author2_role author
author
author
author
author
author_facet Mostafa M. Abbas (17058093)
Paul Soto (18300805)
Latha Ramalingam (18300808)
Yasser El-Manzalawy (5659075)
Halima Bensmail (10400)
Naima Moustaid-Moussa (66960)
author_role author
dc.creator.none.fl_str_mv Mostafa M. Abbas (17058093)
Paul Soto (18300805)
Latha Ramalingam (18300808)
Yasser El-Manzalawy (5659075)
Halima Bensmail (10400)
Naima Moustaid-Moussa (66960)
dc.date.none.fl_str_mv 2022-01-14T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/nu14020349
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Sex_Differences_in_Fish_Oil_and_Olanzapine_Effects_on_Gut_Microbiota_in_Diet-Induced_Obese_Mice/25539583
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Agricultural, veterinary and food sciences
Food sciences
Biomedical and clinical sciences
Nutrition and dietetics
second-generation antipsychotic (SGA)
obesity
fish oil
dc.title.none.fl_str_mv Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and “off-label” indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an “obesogenic” profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37–65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Nutrients<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/nu14020349" target="_blank">https://dx.doi.org/10.3390/nu14020349</a></p>
eu_rights_str_mv openAccess
id Manara2_ae2de35c22783066b76c4bc238256c18
identifier_str_mv 10.3390/nu14020349
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25539583
publishDate 2022
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spelling Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese MiceMostafa M. Abbas (17058093)Paul Soto (18300805)Latha Ramalingam (18300808)Yasser El-Manzalawy (5659075)Halima Bensmail (10400)Naima Moustaid-Moussa (66960)Agricultural, veterinary and food sciencesFood sciencesBiomedical and clinical sciencesNutrition and dieteticssecond-generation antipsychotic (SGA)obesityfish oil<div><p>Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and “off-label” indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an “obesogenic” profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37–65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Nutrients<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/nu14020349" target="_blank">https://dx.doi.org/10.3390/nu14020349</a></p>2022-01-14T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/nu14020349https://figshare.com/articles/journal_contribution/Sex_Differences_in_Fish_Oil_and_Olanzapine_Effects_on_Gut_Microbiota_in_Diet-Induced_Obese_Mice/25539583CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255395832022-01-14T03:00:00Z
spellingShingle Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
Mostafa M. Abbas (17058093)
Agricultural, veterinary and food sciences
Food sciences
Biomedical and clinical sciences
Nutrition and dietetics
second-generation antipsychotic (SGA)
obesity
fish oil
status_str publishedVersion
title Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
title_full Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
title_fullStr Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
title_full_unstemmed Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
title_short Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
title_sort Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice
topic Agricultural, veterinary and food sciences
Food sciences
Biomedical and clinical sciences
Nutrition and dietetics
second-generation antipsychotic (SGA)
obesity
fish oil