• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue T_(reg) cells
【24h】

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue T_(reg) cells

机译：PPAR-γ是脂肪组织T_（reg）细胞积累和表型的主要驱动力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation1. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (T_reg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity~2. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT T_reg cell accumulation, phenotype and function. Unexpectedly, PPAR-y expression by VAT T_reg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of T_reg cells with unique functions can be precisely targeted to therapeutic ends.
机译：在过去的几十年中，肥胖和2型糖尿病的发病率显着上升。这两种疾病之间的主要联系之一是慢性低度炎症1。长时间的营养过量会促进内脏脂肪组织（VAT）以及最终其他组织中白细胞的积累和活化，从而导致代谢异常，例如胰岛素抵抗，2型糖尿病和脂肪肝疾病。尽管促炎性巨噬细胞入侵VAT被认为是驱动脂肪组织炎症和胰岛素抵抗的关键事件，但其他免疫系统细胞在这些过程中的作用知之甚少。最近，有一个独特的增值税驻地调节性T细胞（T_reg）参与了脂肪组织炎症状态的控制，从而使胰岛素敏感性约为2。在这里，我们确定过氧化物酶体增殖物激活受体（PPAR）-γ，脂肪细胞分化的“主调节器”，是VAT T_reg细胞积累，表型和功能的关键分子协调器。出乎意料的是，通过噻唑烷二酮药物吡格列酮完全恢复肥胖小鼠的胰岛素敏感性，必须通过VAT_reg细胞表达PPAR-y。这些发现提示了这一重要的噻唑烷二酮类药物的先前未知的细胞机制，并提供了原理证明具有独特功能的离散T_reg细胞群体可以精确地靶向治疗目的。

著录项

  • 来源
    《Nature》 |2012年第7404期|p.549-553|共5页
  • 作者

    Daniela Cipolletta; Markus Feuere; Amy Li1; Nozomu Kamei; Jongsoon Lee; Steven E. Shoelson; Christophe Benoist; Diane Mathis;

  • 作者单位

    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA,Present addresses: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany (M.F.), The University of Tokyo, Tokyo 113-8655, Japan (N.K.);

    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA,Present addresses: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany (M.F.), The University of Tokyo, Tokyo 113-8655, Japan (N.K.);

    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA;

    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA;

    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号