Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice

Abstract Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with immunomodulatory and anti-inflammatory effects. Beyond its direct effects, the metabolic products of EPA also regulate various immune responses. Animal experiments demonstrated that EPA reduces adipose inflammation in high fat diet-i...

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Autores principales:	Toshiharu Onodera, Atsunori Fukuhara, Jihoon Shin, Tomonori Hayakawa, Michio Otsuki, Iichiro Shimomura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52fdea8ceec344e98b9398d4679dc61c
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spelling	oai:doaj.org-article:52fdea8ceec344e98b9398d4679dc61c2021-12-02T16:08:12ZEicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice10.1038/s41598-017-04474-22045-2322https://doaj.org/article/52fdea8ceec344e98b9398d4679dc61c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04474-2https://doaj.org/toc/2045-2322Abstract Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with immunomodulatory and anti-inflammatory effects. Beyond its direct effects, the metabolic products of EPA also regulate various immune responses. Animal experiments demonstrated that EPA reduces adipose inflammation in high fat diet-induced obese mouse. However, the effects of EPA on infiltrated immune cell populations in adipose tissue and underlying mechanisms remain to be elucidated. We performed flow cytometry of stromal vascular fraction of epididymal adipose tissues from C57BL/6J and ob/ob mice fed normal chow mixed with or without 5% EPA. The numbers of hematopoietic cells, including Tregs, were higher in both C57BL/6J and ob/ob mice fed EPA diet compared with control diet. EPA enhanced the induction of Tregs in co-cultures of adipose tissue macrophages (ATMs) and naïve T cells. Among EPA metabolites, 5-HEPE was the most potent inducer of Tregs. GPR119 and GPR120 are receptors for 5-HEPE and EPA, respectively, and antagonist of GPR119 blocked Treg induction by EPA in the presence of ATMs. Alox5 gene encodes 5-lipoxygenase enzyme catalyzing EPA into 5-HEPE, and inhibitor of 5-lipoxygenase down-regulated EPA-mediated induction of adipose tissue Tregs in ob/ob mice. The study findings demonstrated that both EPA and 5-HEPE enhance ATM-mediated Treg induction.Toshiharu OnoderaAtsunori FukuharaJihoon ShinTomonori HayakawaMichio OtsukiIichiro ShimomuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Toshiharu Onodera Atsunori Fukuhara Jihoon Shin Tomonori Hayakawa Michio Otsuki Iichiro Shimomura Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
description	Abstract Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with immunomodulatory and anti-inflammatory effects. Beyond its direct effects, the metabolic products of EPA also regulate various immune responses. Animal experiments demonstrated that EPA reduces adipose inflammation in high fat diet-induced obese mouse. However, the effects of EPA on infiltrated immune cell populations in adipose tissue and underlying mechanisms remain to be elucidated. We performed flow cytometry of stromal vascular fraction of epididymal adipose tissues from C57BL/6J and ob/ob mice fed normal chow mixed with or without 5% EPA. The numbers of hematopoietic cells, including Tregs, were higher in both C57BL/6J and ob/ob mice fed EPA diet compared with control diet. EPA enhanced the induction of Tregs in co-cultures of adipose tissue macrophages (ATMs) and naïve T cells. Among EPA metabolites, 5-HEPE was the most potent inducer of Tregs. GPR119 and GPR120 are receptors for 5-HEPE and EPA, respectively, and antagonist of GPR119 blocked Treg induction by EPA in the presence of ATMs. Alox5 gene encodes 5-lipoxygenase enzyme catalyzing EPA into 5-HEPE, and inhibitor of 5-lipoxygenase down-regulated EPA-mediated induction of adipose tissue Tregs in ob/ob mice. The study findings demonstrated that both EPA and 5-HEPE enhance ATM-mediated Treg induction.
format	article
author	Toshiharu Onodera Atsunori Fukuhara Jihoon Shin Tomonori Hayakawa Michio Otsuki Iichiro Shimomura
author_facet	Toshiharu Onodera Atsunori Fukuhara Jihoon Shin Tomonori Hayakawa Michio Otsuki Iichiro Shimomura
author_sort	Toshiharu Onodera
title	Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
title_short	Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
title_full	Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
title_fullStr	Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
title_full_unstemmed	Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice
title_sort	eicosapentaenoic acid and 5-hepe enhance macrophage-mediated treg induction in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/52fdea8ceec344e98b9398d4679dc61c
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Eicosapentaenoic acid and 5-HEPE enhance macrophage-mediated Treg induction in mice

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