• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell metabolism >The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity.
【24h】

The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity.

机译：炎性体介导的caspase-1激活控制脂肪细胞分化和胰岛素敏感性。

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-induced inflammation originating from expanding adipose tissue interferes with insulin sensitivity. Important metabolic effects have been recently attributed to IL-1beta and IL-18, two members of the IL-1 family of cytokines. Processing of IL-1beta and IL-18 requires cleavage by caspase-1, a cysteine protease regulated by a protein complex called the inflammasome. We demonstrate that the inflammasome/caspase-1 governs adipocyte differentiation and insulin sensitivity. Caspase-1 is upregulated during adipocyte differentiation and directs adipocytes toward a more insulin-resistant phenotype. Treatment of differentiating adipocytes with recombinant IL-1beta and IL-18, or blocking their effects by inhibitors, reveals that the effects of caspase-1 on adipocyte differentiation are largely conveyed by IL-1beta. Caspase-1 and IL-1beta activity in adipose tissue is increased both in diet-induced and genetically induced obese animal models. Conversely, mice deficient in caspase-1 are more insulin sensitive as compared to wild-type animals. In addition, differentiation of preadipocytes isolated from caspase-1(-/-) or NLRP3(-/-) mice resulted in more metabolically active fat cells. In vivo, treatment of obese mice with a caspase-1 inhibitor significantly increases their insulin sensitivity. Indirect calorimetry analysis revealed higher fat oxidation rates in caspase-1(-/-) animals. In conclusion, the inflammasome is an important regulator of adipocyte function and insulin sensitivity, and caspase-1 inhibition may represent a novel therapeutic target in clinical conditions associated with obesity and insulin resistance.
机译：肥胖引起的源自脂肪组织扩张的炎症会干扰胰岛素敏感性。重要的新陈代谢作用最近归因于IL-1beta和IL-18，这是IL-1细胞因子家族的两个成员。 IL-1beta和IL-18的加工需要被caspase-1裂解，caspase-1是一种被称为炎症小体的蛋白质复合物调节的半胱氨酸蛋白酶。我们证明炎症小体/ caspase-1控制脂肪细胞分化和胰岛素敏感性。 Caspase-1在脂肪细胞分化过程中被上调，并引导脂肪细胞趋向于更具有胰岛素抵抗的表型。用重组IL-1beta和IL-18处理分化的脂肪细胞，或用抑制剂阻断其作用，表明caspase-1对脂肪细胞分化的作用在很大程度上由IL-1beta传递。在饮食诱导和遗传诱导的肥胖动物模型中，脂肪组织中的Caspase-1和IL-1beta活性均增加。相反，与野生型动物相比，缺乏caspase-1的小鼠对胰岛素更敏感。此外，从caspase-1（-/-）或NLRP3（-/-）小鼠中分离的前脂肪细胞的分化导致更多的具有代谢活性的脂肪细胞。在体内，用caspase-1抑制剂治疗肥胖小鼠可显着提高其胰岛素敏感性。间接量热分析显示在caspase-1（-/-）动物中脂肪氧化率更高。总之，炎性小体是脂肪细胞功能和胰岛素敏感性的重要调节剂，在肥胖和胰岛素抵抗相关的临床疾病中，caspase-1的抑制可能代表了新的治疗目标。

著录项

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