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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/11/480 |
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| author | Alma M. Astudillo Clara Meana Miguel A. Bermúdez Alfonso Pérez-Encabo María A. Balboa Jesús Balsinde |
| author_facet | Alma M. Astudillo Clara Meana Miguel A. Bermúdez Alfonso Pérez-Encabo María A. Balboa Jesús Balsinde |
| author_sort | Alma M. Astudillo |
| collection | DOAJ |
| 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 A<sub>2</sub> 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. |
| first_indexed | 2024-03-10T15:03:20Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T15:03:20Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-adadf244280b489e95e62bbecac982e92023-11-20T20:00:41ZengMDPI AGBiomedicines2227-90592020-11-0181148010.3390/biomedicines8110480Release of Anti-Inflammatory Palmitoleic Acid and Its Positional Isomers by Mouse Peritoneal MacrophagesAlma M. Astudillo0Clara Meana1Miguel A. Bermúdez2Alfonso Pérez-Encabo3María A. Balboa4Jesús Balsinde5Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto CINQUIMA, Departamento de Química Orgánica, Universidad de Valladolid, 47011 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainPositional 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 A<sub>2</sub> 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.https://www.mdpi.com/2227-9059/8/11/480palmitoleic acidphospholipid hydrolysisphospholipase A<sub>2</sub>lipid mediatorsfatty acid esters of hydroxy fatty acidsinflammation |
| spellingShingle | Alma M. Astudillo Clara Meana Miguel A. Bermúdez Alfonso Pérez-Encabo María A. Balboa Jesús Balsinde Release of Anti-Inflammatory Palmitoleic Acid and Its Positional Isomers by Mouse Peritoneal Macrophages Biomedicines palmitoleic acid phospholipid hydrolysis phospholipase A<sub>2</sub> lipid mediators fatty acid esters of hydroxy fatty acids inflammation |
| title | 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_short | 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 |
| topic | palmitoleic acid phospholipid hydrolysis phospholipase A<sub>2</sub> lipid mediators fatty acid esters of hydroxy fatty acids inflammation |
| url | https://www.mdpi.com/2227-9059/8/11/480 |
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