宏细胞特异性PPARgamma控制了替代激活,并改善了胰岛素抵抗
Justin I Odegaard1, Roberto R Ricardo-Gonzalez, Matthew H Goforth
1Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5103, USA.
Nature
|May 23, 2007
概括
居住的替代激活巨细胞对于组织修复至关重要,在预防肥胖引起的胰岛素抵抗方面发挥着有益的作用. 向巨细胞两极分化可能为治疗2型糖尿病提供了一种新的策略.
科学领域:
- 代谢综合征和炎症的发生
- 免疫学和新陈代谢
背景情况:
- 肥胖和胰岛素抵抗是代谢综合征的标志,与慢性轻度炎症有关.
- 由巨细胞透引起的脂肪组织炎症加剧了胰岛素抵抗.
- 虽然亲炎性巨细胞得到了充分的研究,但替代激活巨细胞在代谢健康中的作用尚不清楚.
研究的目的:
- 研究替代激活巨细胞在饮食诱导的肥胖和胰岛素抵抗中的作用.
- 确定氧酶增殖器激活受体- (PPARgamma) 在替代性巨细胞激活中的必要性及其对代谢平衡的影响.
主要方法:
- 使用了具有巨细胞特异性删除PPARgamma的小鼠.
- 分析了巨细胞透,脂肪组织炎症,胰岛素敏感性和葡萄糖耐受性.
- 进行了骨肌肉和肝脏的基因表达分析.
主要成果:
- 巨细胞特异性PPARgamma删除损害了替代巨细胞激活.
- 这些小鼠对饮食引起的肥胖,胰岛素耐药性和葡萄糖不耐受性敏感性增加.
- 氧化酸化基因表达在肝脏和肌肉中的下调与胰岛素敏感性降低相关.
结论:
- 替代激活的巨细胞,依赖PPARgamma,在调节营养的恒温中起着保护作用.
- 缺陷的替代性巨细胞两极分化有助于肥胖引起的胰岛素抵抗.
- 促进巨细胞偏向替代状态可能是2型糖尿病的治疗策略.
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