Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of...

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Autores: Carpéné, Christian, Les, Francisco, Mercader, Josep, Gómez Zorita, Saioa, Grolleau, Jean-Louis, Boulet, Nathalie, Fontaine, Jessica, Iglesias-Osma, Mari Carmen, Garcia-Barrado, Maria José
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/42768
Acceso en línea:http://hdl.handle.net/10810/42768
Access Level:acceso abierto
Palabra clave:adipose tissue
obesity
monoamine oxidase
semicarbazide-sensitive amine oxidase
glucose transport
lipotoxicity
insulin
antidepressant
antipsychotic
harmine
phenelzine
opipramol
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spelling Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight ControlCarpéné, ChristianLes, FranciscoMercader, JosepGómez Zorita, SaioaGrolleau, Jean-LouisBoulet, NathalieFontaine, JessicaIglesias-Osma, Mari CarmenGarcia-Barrado, Maria Joséadipose tissueobesitymonoamine oxidasesemicarbazide-sensitive amine oxidaseglucose transportlipotoxicityinsulinantidepressantantipsychoticharminephenelzineopipramolTreatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity.MDPI2020202020202020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/42768reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.mdpi.com/1424-8247/13/3/41info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).oai:addi.ehu.eus:10810/427682026-06-18T09:23:17Z
dc.title.none.fl_str_mv Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
title Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
spellingShingle Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
Carpéné, Christian
adipose tissue
obesity
monoamine oxidase
semicarbazide-sensitive amine oxidase
glucose transport
lipotoxicity
insulin
antidepressant
antipsychotic
harmine
phenelzine
opipramol
title_short Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
title_full Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
title_fullStr Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
title_full_unstemmed Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
title_sort Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control
dc.creator.none.fl_str_mv Carpéné, Christian
Les, Francisco
Mercader, Josep
Gómez Zorita, Saioa
Grolleau, Jean-Louis
Boulet, Nathalie
Fontaine, Jessica
Iglesias-Osma, Mari Carmen
Garcia-Barrado, Maria José
author Carpéné, Christian
author_facet Carpéné, Christian
Les, Francisco
Mercader, Josep
Gómez Zorita, Saioa
Grolleau, Jean-Louis
Boulet, Nathalie
Fontaine, Jessica
Iglesias-Osma, Mari Carmen
Garcia-Barrado, Maria José
author_role author
author2 Les, Francisco
Mercader, Josep
Gómez Zorita, Saioa
Grolleau, Jean-Louis
Boulet, Nathalie
Fontaine, Jessica
Iglesias-Osma, Mari Carmen
Garcia-Barrado, Maria José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv adipose tissue
obesity
monoamine oxidase
semicarbazide-sensitive amine oxidase
glucose transport
lipotoxicity
insulin
antidepressant
antipsychotic
harmine
phenelzine
opipramol
topic adipose tissue
obesity
monoamine oxidase
semicarbazide-sensitive amine oxidase
glucose transport
lipotoxicity
insulin
antidepressant
antipsychotic
harmine
phenelzine
opipramol
description Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/42768
url http://hdl.handle.net/10810/42768
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.mdpi.com/1424-8247/13/3/41
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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