12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice

Abstract Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by...

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Autores principales:	Takahiro Nagatake, Yuki Shibata, Sakiko Morimoto, Eri Node, Kento Sawane, So-ichiro Hirata, Jun Adachi, Yuichi Abe, Junko Isoyama, Azusa Saika, Koji Hosomi, Takeshi Tomonaga, Jun Kunisawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46db4e714e7349749bbe4ce5c4ec444c
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spelling	oai:doaj.org-article:46db4e714e7349749bbe4ce5c4ec444c2021-12-02T15:45:31Z12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice10.1038/s41598-021-89707-12045-2322https://doaj.org/article/46db4e714e7349749bbe4ce5c4ec444c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89707-1https://doaj.org/toc/2045-2322Abstract Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.Takahiro NagatakeYuki ShibataSakiko MorimotoEri NodeKento SawaneSo-ichiro HirataJun AdachiYuichi AbeJunko IsoyamaAzusa SaikaKoji HosomiTakeshi TomonagaJun KunisawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takahiro Nagatake Yuki Shibata Sakiko Morimoto Eri Node Kento Sawane So-ichiro Hirata Jun Adachi Yuichi Abe Junko Isoyama Azusa Saika Koji Hosomi Takeshi Tomonaga Jun Kunisawa 12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
description	Abstract Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.
format	article
author	Takahiro Nagatake Yuki Shibata Sakiko Morimoto Eri Node Kento Sawane So-ichiro Hirata Jun Adachi Yuichi Abe Junko Isoyama Azusa Saika Koji Hosomi Takeshi Tomonaga Jun Kunisawa
author_facet	Takahiro Nagatake Yuki Shibata Sakiko Morimoto Eri Node Kento Sawane So-ichiro Hirata Jun Adachi Yuichi Abe Junko Isoyama Azusa Saika Koji Hosomi Takeshi Tomonaga Jun Kunisawa
author_sort	Takahiro Nagatake
title	12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
title_short	12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
title_full	12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
title_fullStr	12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
title_full_unstemmed	12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
title_sort	12-hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/46db4e714e7349749bbe4ce5c4ec444c
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12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice

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