增加脂肪细胞O2消耗触发HIF-1α,导致炎症和胰岛素抵抗在肥胖中
Yun Sok Lee1, Jung-Whan Kim2, Olivia Osborne1
1Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|June 7, 2014
概括
肥胖会通过脂肪组织缺氧引起胰岛素抵抗. 阻止ANT2或HIF-1α可以防止这种情况,恢复胰岛素敏感性和葡萄糖耐受性.
科学领域:
- 代谢性疾病是一种代谢性疾病.
- 肥胖研究的研究.
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 脂肪组织缺氧和炎症与肥胖引起的胰岛素抵抗有关.
- 启动这种级联的精确分子机制仍然不完全理解.
研究的目的:
- 阐明早期的分子事件,将高脂肪饮食 (HFD) 食与脂肪组织缺氧,炎症和胰岛素抵抗联系起来.
- 确定治疗干预的关键分子标.
主要方法:
- 在动物中使用高脂肪饮食 (HFD) 养模型.
- 研究了脂肪细胞呼吸,氧气消耗和缺氧诱导因子1-alpha (HIF-1α) 的诱导.
- 研究了腺因核酸转位酶2 (ANT2) 在调解和脂肪酸效应中的作用.
- 评估了ANT2和HIF-1α的遗传或药理抑制对代谢参数的影响.
主要成果:
- HFD养诱导了未合的脂肪细胞呼吸,导致缺氧和HIF-1α激活.
- 和脂肪酸刺激了线粒体蛋白质ANT2,导致了脱呼吸.
- 抑制ANT2或HIF-1α改善了脂肪组织炎症和胰岛素抵抗.
- 在干预后观察到恢复胰岛素敏感性和改善葡萄糖耐受性.
结论:
- 脂肪细胞线粒体功能障碍,由ANT2和和脂肪酸介导,在肥胖中启动缺氧和炎症.
- 向ANT2或HIF-1α代表了肥胖引起的胰岛素耐药性的潜在治疗策略.
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