Protein Inhibitor of Activated STAT 1 (PIAS1) Protects Against Obesity-Induced Insulin Resistance by Inhibiting Inflammation Cascade in Adipose Tissue

DOI PDF PDF 被引用文献1件
  • Yang Liu
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Xin Ge
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Xin Dou
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Liang Guo
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Yuan Liu
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Shui-rong Zhou
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Xiang-bo Wei
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Shu-wen Qian
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Hai-yan Huang
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Cong-jian Xu
    Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
  • Wei-Ping Jia
    Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China
  • Yong-jun Dang
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Xi Li
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China
  • Qi-qun Tang
    Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China

書誌事項

公開日
2015-08-31
権利情報
  • http://www.diabetesjournals.org/site/license
DOI
  • 10.2337/db15-0278
公開者
American Diabetes Association

この論文をさがす

説明

<jats:p>Obesity is associated with chronic low-level inflammation, especially in fat tissues, which contributes to insulin resistance and type 2 diabetes mellitus (T2DM). Protein inhibitor of activated STAT 1 (PIAS1) modulates a variety of cellular processes such as cell proliferation and DNA damage responses. Particularly, PIAS1 functions in the innate immune system and is a key regulator of the inflammation cascade. However, whether PIAS1 is involved in the regulation of insulin sensitivity remains unknown. Here, we demonstrated that PIAS1 expression in white adipose tissue (WAT) was downregulated by c-Jun N-terminal kinase in prediabetic mice models. Overexpression of PIAS1 in inguinal WAT of prediabetic mice significantly improved systemic insulin sensitivity, whereas knockdown of PIAS1 in wild-type mice led to insulin resistance. Mechanistically, PIAS1 inhibited the activation of stress-induced kinases and the expression of nuclear factor-κB target genes in adipocytes, mainly including proinflammatory and chemotactic factors. In doing so, PIAS1 inhibited macrophage infiltration in adipose tissue, thus suppressing amplification of the inflammation cascade, which in turn improved insulin sensitivity. These results were further verified in a fat transplantation model. Our findings shed light on the critical role of PIAS1 in controlling insulin sensitivity and suggest a therapeutic potential of PIAS1 in T2DM.</jats:p>

収録刊行物

  • Diabetes

    Diabetes 64 (12), 4061-4074, 2015-08-31

    American Diabetes Association

被引用文献 (1)*注記

もっと見る

問題の指摘

ページトップへ