Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver

Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)...

Descripción completa

Detalles Bibliográficos
Autores: Ferreira, Vítor, Folgueira, Cintia, Montes-San Lorenzo, Ángela, Rodríguez-López, Andrea, Gonzalez-Iglesias, Eva, Zubiaur, Pablo, Abad-Santos, Francisco, Sabio, Guadalupe, Rada, Patricia, Valverde, Ángela M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/371330
Acceso en línea:http://hdl.handle.net/10261/371330
Access Level:acceso abierto
Palabra clave:Olanzapine
Estrogens
Hypothalamus
Inter-organ crosstalk
Liver
Thermogenesis
id ES_6fd4fa84f08b0d291671d3cae4f2106e
oai_identifier_str oai:digital.csic.es:10261/371330
network_acronym_str ES
network_name_str España
repository_id_str
spelling Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liverFerreira, VítorFolgueira, CintiaMontes-San Lorenzo, ÁngelaRodríguez-López, AndreaGonzalez-Iglesias, EvaZubiaur, PabloAbad-Santos, FranciscoSabio, GuadalupeRada, PatriciaValverde, Ángela M.OlanzapineEstrogensHypothalamusInter-organ crosstalkLiverThermogenesisOlanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17β-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.This work was funded by grants PID2021-122766OB-I00 (to AMV) and PID2019-104399RB-I00 (to GS) funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe” by the European Union (Spain). We also acknowledge grants H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement 721236, European Commission) (to AMV and FA-S), and P2022/BMD-7227 (Comunidad de Madrid, Spain), and CIBERdem (ISCIII, Spain) (to AMV). VF was a recipient of a contract from ITN-TREATMENT and a PhD fellowship from the Portuguese Foundation for Science and Technology (2020.08388.BD, FCT, Portugal)/ERDF. CF was awarded with Sara Borrell contract (CD19/00078, ISCIII, Spain).Peer reviewedMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionComunidad de MadridFundação para a Ciência e a Tecnologia (Portugal)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/371330reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122766OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104399RB-I00info:eu-repo/grantAgreement/EC/H2020/721236P2022/BMD-7227https://doi.org/10.1016/j.bbadis.2024.167227Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3713302026-05-22T06:33:51Z
dc.title.none.fl_str_mv Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
title Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
spellingShingle Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
Ferreira, Vítor
Olanzapine
Estrogens
Hypothalamus
Inter-organ crosstalk
Liver
Thermogenesis
title_short Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
title_full Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
title_fullStr Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
title_full_unstemmed Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
title_sort Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
dc.creator.none.fl_str_mv Ferreira, Vítor
Folgueira, Cintia
Montes-San Lorenzo, Ángela
Rodríguez-López, Andrea
Gonzalez-Iglesias, Eva
Zubiaur, Pablo
Abad-Santos, Francisco
Sabio, Guadalupe
Rada, Patricia
Valverde, Ángela M.
author Ferreira, Vítor
author_facet Ferreira, Vítor
Folgueira, Cintia
Montes-San Lorenzo, Ángela
Rodríguez-López, Andrea
Gonzalez-Iglesias, Eva
Zubiaur, Pablo
Abad-Santos, Francisco
Sabio, Guadalupe
Rada, Patricia
Valverde, Ángela M.
author_role author
author2 Folgueira, Cintia
Montes-San Lorenzo, Ángela
Rodríguez-López, Andrea
Gonzalez-Iglesias, Eva
Zubiaur, Pablo
Abad-Santos, Francisco
Sabio, Guadalupe
Rada, Patricia
Valverde, Ángela M.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Comunidad de Madrid
Fundação para a Ciência e a Tecnologia (Portugal)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Olanzapine
Estrogens
Hypothalamus
Inter-organ crosstalk
Liver
Thermogenesis
topic Olanzapine
Estrogens
Hypothalamus
Inter-organ crosstalk
Liver
Thermogenesis
description Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17β-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/371330
url http://hdl.handle.net/10261/371330
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122766OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104399RB-I00
info:eu-repo/grantAgreement/EC/H2020/721236
P2022/BMD-7227
https://doi.org/10.1016/j.bbadis.2024.167227
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410536727248897
score 15,811543

Similares en LA Referencia