دورية أكاديمية
NK cells induce hepatic ER stress to promote insulin resistance in obesity through osteopontin production
| العنوان: | NK cells induce hepatic ER stress to promote insulin resistance in obesity through osteopontin production |
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| المؤلفون: | Wu, Junhua, Wu, Danyang, Zhang, Longyao, Lin, Chuxuan, Liao, Jiahao, Xie, Ruyin, Li, Zhulin, Wu, Siyang, Liu, Aimin, Hu, Weining, Xi, Yang, Bu, Shizhong, Wang, Fuyan |
| المساهمون: | Natural Science Foundation of Zhejiang Province, National Natural Science Foundation of China, Ningbo Science and Technology Innovation Team Program, Natural Science Foundation of Ningbo Municipality, Natural Science Foundation of Ningbo |
| المصدر: | Journal of Leukocyte Biology ; volume 107, issue 4, page 589-596 ; ISSN 1938-3673 0741-5400 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cell Biology, Immunology, Immunology and Allergy |
| الوصف: | High-fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD-fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+DX5– tissue-resident NK (trNK) cells. Obesity-induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD-fed mice. OPN treatment enhances the expression of ER stress markers, including p-PERK, p-eIF2, ATF4, and CHOP in both murine liver tissues and HL-7702, a human liver cell line. Pretreatment of HL-7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity-induced hepatic ER stress, and IR through OPN production. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/jlb.3ma1119-173r |
| DOI: | 10.1002/JLB.3MA1119-173R |
| الإتاحة: | https://doi.org/10.1002/jlb.3ma1119-173rTest https://academic.oup.com/jleukbio/article-pdf/107/4/589/48795867/jlb10522.pdfTest |
| حقوق: | https://academic.oup.com/pages/standard-publication-reuse-rightsTest ; http://onlinelibrary.wiley.com/termsAndConditions#vorTest ; http://doi.wiley.com/10.1002/tdm_license_1.1Test |
| رقم الانضمام: | edsbas.773D1D57 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/jlb.3ma1119-173r |
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