Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells

Masuyama, Satoshi; Mizui, Masayuki; Morita, Masashi; Shigeki, Takatomo; Kato, Hisakazu; Yamamoto, Takeshi; Sakaguchi, Yusuke; Inoue, Kazunori; Namba-Hamano, Tomoko; Matsui, Isao; Okuno, Tatsusada; Yamamoto, Ryohei; Takashima, Seiji; Isaka, Yoshitaka

doi:https://doi.org/10.1016/j.clim.2024.110357

Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells

Masuyama, Satoshi; Mizui, Masayuki; Morita, Masashi et al.

Clinical Immunology, 2024, 268, 110357

Number of Access:2,773（2025-08-14 03:49 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98432

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Title	Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells
Creator	CreatorName Masuyama, Satoshi
	NRID 1000030423106 1000030423106 ORCID 0000-0003-2543-8108 0000-0003-2543-8108 researchmap permalink msmizui msmizui Scopus Author ID 8935909200 8935909200 CreatorName Mizui, Masayuki
	NRID 1000060817659 1000060817659 CreatorName Morita, Masashi
	CreatorName Shigeki, Takatomo
	NRID 1000030589312 1000030589312 ORCID 0000-0003-4619-3680 0000-0003-4619-3680 researchmap permalink kato-hisa-1979 kato-hisa-1979 Scopus Author ID 55476241300 55476241300 CreatorName Kato, Hisakazu
	NRID 1000020756994 1000020756994 ORCID 0009-0007-3817-0557 0009-0007-3817-0557 researchmap permalink tyamamoto-handai3857 tyamamoto-handai3857 Scopus Author ID 55628566248 55628566248 CreatorName Yamamoto, Takeshi
	NRID 1000080756817 1000080756817 researchmap permalink sakaguchi-handai3857 sakaguchi-handai3857 Scopus Author ID 35183980700 35183980700 ORCID 0000-0002-0987-5423 0000-0002-0987-5423 CreatorName Sakaguchi, Yusuke
	NRID 1000010631301 1000010631301 researchmap permalink kznri kznri Scopus Author ID 55124465800 55124465800 CreatorName Inoue, Kazunori
	NRID 1000030734420 1000030734420 researchmap permalink namba-handai3857 namba-handai3857 Scopus Author ID 8577526800 8577526800 CreatorName Namba-Hamano, Tomoko
	NRID 1000060456986 1000060456986 ORCID 0000-0001-8378-6130 0000-0001-8378-6130 researchmap permalink matsui-handai3857 matsui-handai3857 Scopus Author ID 24488796300 24488796300 CreatorName Matsui, Isao
	NRID 1000000464248 1000000464248 researchmap permalink neuroimmunology neuroimmunology Scopus Author ID 9736132000 9736132000 CreatorName Okuno, Tatsusada
	NRID 1000000533853 1000000533853 ORCID 0000-0003-2610-9824 0000-0003-2610-9824 researchmap permalink yamamotor yamamotor Scopus Author ID 13104281900 13104281900 CreatorName Yamamoto, Ryohei
	NRID 1000090379272 1000090379272 researchmap permalink read0118567 read0118567 Scopus Author ID 7402272558 7402272558 CreatorName Takashima, Seiji
	NRID 1000000379166 1000000379166 researchmap permalink isaka-handai3857 isaka-handai3857 Scopus Author ID 16207611100 16207611100 ORCID 0000-0002-0820-7167 0000-0002-0820-7167 CreatorName Isaka, Yoshitaka
Subject	Autoimmunity
	FAO
	Glutaminolysis
	PPARα
	Th17
Description	Masuyama S., Mizui M., Morita M., et al. Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells. Clinical Immunology 268, 110357 (2024); https://doi.org/10.1016/j.clim.2024.110357.
Abstract	While fatty acid oxidation (FAO) in mitochondria is a primary energy source for quiescent lymphocytes, the impact of promoting FAO in activated lymphocytes undergoing metabolic reprogramming remains unclear. Here, we demonstrate that pemafibrate, a selective PPARα modulator used clinically for the treatment of hypertriglyceridemia, transforms metabolic system of T-cells and alleviates several autoimmune diseases. Pemafibrate suppresses Th17 cells but not Th1 cells, through the inhibition of glutaminolysis and glycolysis initiated by enhanced FAO. In contrast, a conventional PPARα agonist fenofibrate significantly inhibits cell growth by restraining overall metabolisms even at a dose insufficient to induce fatty acid oxidation. Clinically, patients receiving pemafibrate showed a significant decrease of Th17/Treg ratio in peripheral blood. Our results suggest that augmented FAO by pemafibrate-mediated selective activation of PPARα restrains metabolic programs of Th17 cells and could be a viable option for the treatment of autoimmune diseases.
Publisher	Elsevier B.V.
Source Title	Clinical Immunology
Volume (Issue)	268
Page	110357
Date of Issued	2024-11-01
Language	English
Handle URL	https://hdl.handle.net/11094/98432
PISSN	15216616
eISSN	15217035
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.clim.2024.110357
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Clinical Immunology. 2024, 268, p. 110357
DC.title	Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells
DC.creator	Masuyama, Satoshi
	Mizui, Masayuki
	Morita, Masashi
	Shigeki, Takatomo
	Kato, Hisakazu
	Yamamoto, Takeshi
	Sakaguchi, Yusuke
	Inoue, Kazunori
	Namba-Hamano, Tomoko
	Matsui, Isao
	Okuno, Tatsusada
	Yamamoto, Ryohei
	Takashima, Seiji
	Isaka, Yoshitaka
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-11-01
DC.identifier	https://doi.org/10.1016/j.clim.2024.110357
DC.subject	Autoimmunity
	FAO
	Glutaminolysis
	PPARα
	Th17
DC.description	Masuyama S., Mizui M., Morita M., et al. Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells. Clinical Immunology 268, 110357 (2024); https://doi.org/10.1016/j.clim.2024.110357.
DCTERMS.abstract	While fatty acid oxidation (FAO) in mitochondria is a primary energy source for quiescent lymphocytes, the impact of promoting FAO in activated lymphocytes undergoing metabolic reprogramming remains unclear. Here, we demonstrate that pemafibrate, a selective PPARα modulator used clinically for the treatment of hypertriglyceridemia, transforms metabolic system of T-cells and alleviates several autoimmune diseases. Pemafibrate suppresses Th17 cells but not Th1 cells, through the inhibition of glutaminolysis and glycolysis initiated by enhanced FAO. In contrast, a conventional PPARα agonist fenofibrate significantly inhibits cell growth by restraining overall metabolisms even at a dose insufficient to induce fatty acid oxidation. Clinically, patients receiving pemafibrate showed a significant decrease of Th17/Treg ratio in peripheral blood. Our results suggest that augmented FAO by pemafibrate-mediated selective activation of PPARα restrains metabolic programs of Th17 cells and could be a viable option for the treatment of autoimmune diseases.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98432
citation_title	Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells
citation_author	Masuyama, Satoshi
	Mizui, Masayuki
	Morita, Masashi
	Shigeki, Takatomo
	Kato, Hisakazu
	Yamamoto, Takeshi
	Sakaguchi, Yusuke
	Inoue, Kazunori
	Namba-Hamano, Tomoko
	Matsui, Isao
	Okuno, Tatsusada
	Yamamoto, Ryohei
	Takashima, Seiji
	Isaka, Yoshitaka
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2024-11-01
citation_journal_title	Clinical Immunology
citation_volume	268
citation_firstpage	110357
citation_doi	https://doi.org/10.1016/j.clim.2024.110357
citation_public_url	https://hdl.handle.net/11094/98432

Enhanced fatty acid oxidation by selective activation of PPARα alleviates autoimmunity through metabolic transformation in T-cells

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