Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2.
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2.
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DOI：
10.1038/s41598-021-85080-1
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发表时间：
2021-03-16
影响因子：
4.6
通讯作者：
Wada J
中科院分区：
文献类型：
--
作者：
Nunoue T;Yamaguchi S;Teshigawara S;Katayama A;Nakatsuka A;Eguchi J;Niki T;Wada J
脂肪组织被认为是一种内分泌器官，分泌具有生物活性的脂肪因子，调节肥胖症的慢性炎症和氧化应激。Gal-9在细胞损伤时分泌出来，与T细胞免疫球蛋白-3（Tim-3）相互作用并诱导活化的Th 1细胞的凋亡。Gal-9还结合蛋白质二硫键异构酶（PDI），维持T细胞表面上的PDI，并增加二硫键/巯基循环中的游离巯基。为了探索肥胖的分子机制，我们研究了喂食高脂肪高蔗糖（HFHS）食物的Gal-9−/−和Gal-9 wt/wt C57 BL/6 J小鼠。与Gal-9 wt/wt小鼠相比，Gal-9−/−小鼠对与附睾和肠系膜脂肪组织减少相关的饮食诱导的肥胖具有抗性，并改善了葡萄糖耐量。然而，附睾脂肪中M1、M2巨噬细胞的数量和M1/M2比率没有改变。在HFHS食物下，接受Gal-9 −/−或Gal-9 wt/wt骨髓衍生细胞（BMC）的Gal-9−/−小鼠的体重显著低于接受Gal-9−/− BMC的Gal-9 wt/wt小鼠。我们通过nanoLC-MS/MS、免疫沉淀和pull-down测定以糖链非依赖性方式鉴定了Gal-9和过氧化物氧还蛋白-2（PRDX 2）之间的结合。在3 T3 L1脂肪细胞中，Gal-9敲低在H2 O2的氧化应激下使PRDX 2单体（还原形式）从PRDX 2二聚体（氧化形式）占主导地位。抑制脂肪细胞中的Gal-9可能是针对肥胖症中的氧化应激和随后的葡萄糖耐受不良的新的治疗方法。
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.
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DOI：
10.1074/jbc.ra117.001254
发表时间：
2018-05-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fazakerley DJ;Minard AY;Krycer JR;Thomas KC;Stöckli J;Harney DJ;Burchfield JG;Maghzal GJ;Caldwell ST;Hartley RC;Stocker R;Murphy MP;James DE
通讯作者：
James DE
影响因子：
3
作者：
Hirashima, M;Kashio, Y;Nakamura, T
通讯作者：
Nakamura, T
影响因子：
3.7
作者：
Moritoki M;Kadowaki T;Niki T;Nakano D;Soma G;Mori H;Kobara H;Masaki T;Kohno M;Hirashima M
通讯作者：
Hirashima M
影响因子：
3
作者：
Maslov LN;Naryzhnaya NV;Boshchenko AA;Popov SV;Ivanov VV;Oeltgen PR
通讯作者：
Oeltgen PR
影响因子：
5.6
作者：
Lai JH;Luo SF;Wang MY;Ho LJ
通讯作者：
Ho LJ