Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2

Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-...

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Autores principales:	Tomokazu Nunoue, Satoshi Yamaguchi, Sanae Teshigawara, Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Toshiro Niki, Jun Wada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/110c99ec57ae431286337d47e898548a
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spelling	oai:doaj.org-article:110c99ec57ae431286337d47e898548a2021-12-02T13:17:55ZLgals9 deficiency ameliorates obesity by modulating redox state of PRDX210.1038/s41598-021-85080-12045-2322https://doaj.org/article/110c99ec57ae431286337d47e898548a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85080-1https://doaj.org/toc/2045-2322Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.Tomokazu NunoueSatoshi YamaguchiSanae TeshigawaraAkihiro KatayamaAtsuko NakatsukaJun EguchiToshiro NikiJun WadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
description	Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.
format	article
author	Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada
author_facet	Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada
author_sort	Tomokazu Nunoue
title	Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
title_short	Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
title_full	Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
title_fullStr	Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
title_full_unstemmed	Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
title_sort	lgals9 deficiency ameliorates obesity by modulating redox state of prdx2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/110c99ec57ae431286337d47e898548a
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Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2

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