Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages
Positional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known of them, palmitoleic acid (cis-9-hexadecenoic acid, 16:1n-7), has been identified as a lipokine with important beneficial actions in metabolic diseases. Hypogeic acid (cis-7-hexade...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/230617 |
| Acceso en línea: | http://hdl.handle.net/10261/230617 |
| Access Level: | acceso abierto |
| Palabra clave: | Palmitoleic acid Phospholipid hydrolysis Phospholipase A2 Lipid mediators Fatty acid esters of hydroxy fatty acids Inflammation Monocytes/macrophages |
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Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophagesAstudillo, Alma M.Meana, ClaraBermúdez, Miguel A.Pérez-Encabo, AlfonsoBalboa, María A.Balsinde, JesúsPalmitoleic acidPhospholipid hydrolysisPhospholipase A2Lipid mediatorsFatty acid esters of hydroxy fatty acidsInflammationMonocytes/macrophagesPositional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known of them, palmitoleic acid (cis-9-hexadecenoic acid, 16:1n-7), has been identified as a lipokine with important beneficial actions in metabolic diseases. Hypogeic acid (cis-7-hexadecenoic acid, 16:1n-9) has been regarded as a possible biomarker of foamy cell formation during atherosclerosis. Notwithstanding the importance of these isomers as possible regulators of inflammatory responses, very little is known about the regulation of their levels and distribution and mobilization among the different lipid pools within the cell. In this work, we describe that the bulk of hexadecenoic fatty acids found in mouse peritoneal macrophages is esterified in a unique phosphatidylcholine species, which contains palmitic acid at the sn-1 position, and hexadecenoic acid at the sn-2 position. This species markedly decreases when the macrophages are activated with inflammatory stimuli, in parallel with net mobilization of free hexadecenoic acid. Using pharmacological inhibitors and specific gene-silencing approaches, we demonstrate that hexadecenoic acids are selectively released by calcium-independent group VIA phospholipase A2 under activation conditions. While most of the released hexadecenoic acid accumulates in free fatty acid form, a significant part is also transferred to other phospholipids to form hexadecenoate-containing inositol phospholipids, which are known to possess growth-factor-like-properties, and are also used to form fatty acid esters of hydroxy fatty acids, compounds with known anti-diabetic and anti-inflammatory properties. Collectively, these data unveil new pathways and mechanisms for the utilization of palmitoleic acid and its isomers during inflammatory conditions, and raise the intriguing possibility that part of the anti-inflammatory activity of these fatty acids may be due to conversion to other lipid mediators.This research was funded by the Spanish Ministry of Science and Innovation, grant numbers SAF2016-80883-R and PID2019-105989RB-I00. M.A.B. (Miguel A. Bermúdez) was supported by a predoctoral fellowship from the Spanish Ministry of Science and Innovation. CIBERDEM is an initiative of Instituto de Salud Carlos III.Multidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/230617reponame: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#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-80883-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105989RB-I00PID2019-105989RB-I00/AEI/10.13039/501100011033http://dx.doi.org/10.3390/biomedicines8110480Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2306172026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| title |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| spellingShingle |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages Astudillo, Alma M. Palmitoleic acid Phospholipid hydrolysis Phospholipase A2 Lipid mediators Fatty acid esters of hydroxy fatty acids Inflammation Monocytes/macrophages |
| title_short |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| title_full |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| title_fullStr |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| title_full_unstemmed |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| title_sort |
Release of anti-inflammatory palmitoleic acid and its positional isomers by mouse peritoneal macrophages |
| dc.creator.none.fl_str_mv |
Astudillo, Alma M. Meana, Clara Bermúdez, Miguel A. Pérez-Encabo, Alfonso Balboa, María A. Balsinde, Jesús |
| author |
Astudillo, Alma M. |
| author_facet |
Astudillo, Alma M. Meana, Clara Bermúdez, Miguel A. Pérez-Encabo, Alfonso Balboa, María A. Balsinde, Jesús |
| author_role |
author |
| author2 |
Meana, Clara Bermúdez, Miguel A. Pérez-Encabo, Alfonso Balboa, María A. Balsinde, Jesús |
| author2_role |
author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) Instituto de Salud Carlos III Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Palmitoleic acid Phospholipid hydrolysis Phospholipase A2 Lipid mediators Fatty acid esters of hydroxy fatty acids Inflammation Monocytes/macrophages |
| topic |
Palmitoleic acid Phospholipid hydrolysis Phospholipase A2 Lipid mediators Fatty acid esters of hydroxy fatty acids Inflammation Monocytes/macrophages |
| description |
Positional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known of them, palmitoleic acid (cis-9-hexadecenoic acid, 16:1n-7), has been identified as a lipokine with important beneficial actions in metabolic diseases. Hypogeic acid (cis-7-hexadecenoic acid, 16:1n-9) has been regarded as a possible biomarker of foamy cell formation during atherosclerosis. Notwithstanding the importance of these isomers as possible regulators of inflammatory responses, very little is known about the regulation of their levels and distribution and mobilization among the different lipid pools within the cell. In this work, we describe that the bulk of hexadecenoic fatty acids found in mouse peritoneal macrophages is esterified in a unique phosphatidylcholine species, which contains palmitic acid at the sn-1 position, and hexadecenoic acid at the sn-2 position. This species markedly decreases when the macrophages are activated with inflammatory stimuli, in parallel with net mobilization of free hexadecenoic acid. Using pharmacological inhibitors and specific gene-silencing approaches, we demonstrate that hexadecenoic acids are selectively released by calcium-independent group VIA phospholipase A2 under activation conditions. While most of the released hexadecenoic acid accumulates in free fatty acid form, a significant part is also transferred to other phospholipids to form hexadecenoate-containing inositol phospholipids, which are known to possess growth-factor-like-properties, and are also used to form fatty acid esters of hydroxy fatty acids, compounds with known anti-diabetic and anti-inflammatory properties. Collectively, these data unveil new pathways and mechanisms for the utilization of palmitoleic acid and its isomers during inflammatory conditions, and raise the intriguing possibility that part of the anti-inflammatory activity of these fatty acids may be due to conversion to other lipid mediators. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2021 2021 2021 |
| 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/10261/230617 |
| url |
http://hdl.handle.net/10261/230617 |
| 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# info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-80883-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105989RB-I00 PID2019-105989RB-I00/AEI/10.13039/501100011033 http://dx.doi.org/10.3390/biomedicines8110480 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Multidisciplinary Digital Publishing Institute |
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Multidisciplinary Digital Publishing Institute |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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