肝肠轴信号调节轮班工人的昼夜能量代谢
Zhenning Yang1,2, Helmut Zarbl2,3, Bo Kong1
1Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
概括
轮班工作扰乱昼夜节律,影响代谢平衡. 纤维细胞生长因子15/19 (FGF15/19) 在调节昼夜能量代谢方面发挥作用,可能是代谢疾病的目标.
科学领域:
- 代谢的恒常状态 (metabolic homeostasis) 是指代谢过程中的恒常状态.
- 时间生物学 时间生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 轮班工作的循环节律扰乱是代谢疾病的危险因素.
- 纤维细胞生长因子15/19 (FGF15/19) 对肝肠轴功能,胆酸合成和胰岛素敏感性至关重要.
- 赛尔图因1 (SIRT1) 将肝脏新陈代谢与昼夜节律联系起来,维持肝脏平衡.
研究的目的:
- 研究夜班工作对人类昼夜节律,FGF19,胆酸概况和SIRT1信号传递的影响.
- 探索FGF15在调节小鼠昼夜节律和肝脏代谢中的作用.
- 评估FGF15/19作为轮班工作引起的代谢障碍的潜在治疗标.
主要方法:
- 临床研究比较夜班 (NS) 和日班 (DS) 护士.
- 使用复合FGF19蛋白和SIRT1抑制剂的体外实验.
- 在体内研究野生型 (WT),Fgf15淘汰 (KO) 和Fgf15转基因 (TG) 的小鼠.
主要成果:
- 夜班护士表现出乱的昼夜节律,血FGF19和胆酸水平的改变,以及SIRT1信号的受损.
- FGF19蛋白在试验室中挽救了破坏的细胞昼夜节律.
- 在小鼠中,Fgf15缺乏导致SIRT1信号传递,胆酸和脂质代谢以及炎症相关的基因的昼夜表达受损,夜间SIRT1信号传递减少.
结论:
- FGF15/19在调节昼夜能量代谢方面发挥着重要作用.
- FGF15/19可以作为与慢性轮班工作相关的代谢疾病的预后生物标志物和治疗标.
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