肥胖会破坏 pituitary-hepatic UPR 通信,导致 NAFLD 的进展
Qingwen Qian1, Mark Li1, Zeyuan Zhang1
1Department of Anatomy and Cell Biology, Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Cell metabolism
|May 8, 2024
概括
肥胖会损害垂体腺功能,扰乱对预防非酒精性脂肪肝疾病 (NAFLD) 至关重要的通信. 激活特定的肝脏通路可以改善肥胖个体的NAFLD.
科学领域:
- 内分泌学 在内分泌学.
- 代谢疾病 代谢疾病
- 免疫学 免疫学 免疫学
背景情况:
- 肥胖破坏了调节肝脏免疫代谢平衡的垂体激素,导致非酒精性脂肪肝疾病 (NAFLD).
- 肥胖对 pituitary 腺体内部细胞环境的影响在很大程度上仍未被探索.
研究的目的:
- 为了研究肥胖对内恒温的影响.
- 阐明通过展开蛋白质响应 (UPR) 途径在NAFLD病变发生过程中的垂体-肝脏通信的作用.
主要方法:
- 来自肥胖和对照小鼠和人类的垂体腺体的分析.
- 对需要内醇的酶1α (IRE1α) -X盒结合蛋白1 (XBP1) UPR通路的研究.
- 在小鼠模型中进行基因操纵 (IRE1删除) 和肝通路的药理激活.
主要成果:
- 肥胖的受试者表现出的UPR和脑下垂体的炎症加剧.
- 在肥胖症中缺陷的垂体IRE1α-XBP1信号传递有助于内分泌缺陷和NAFLD进展.
- 甲状腺特异性的IRE1缺失导致甲状腺功能低下,并减少肝脏XBP1激活;激活肝脏THRB-XBP1轴改善NAFLD.
结论:
- 肥胖会导致脑下垂体内的细胞缺陷.
- 垂体-肝脏UPR通信是NAFLD发展和进展的关键因素.
- 针对肝脏THRB-XBP1轴为下垂体功能障碍的背景下NAFLD提供了潜在的治疗策略.
关键词:
爱尔兰的第一名.这是NAFLD.通过UPR进行全日制检查.肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary pituitary甲状腺激素是甲状腺激素的一种.
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