Wang Yan, Li Xianhui, He Zhi, Chen Wenwei, Lu Jiewen
Pharmazie. 2016 Dec 1;71(12):733-737. doi: 10.1691/ph.2016.6695.
Rapamycin (Rap), a specific inhibitor of the mTOR signaling, has been shown to affect lipid metabolism in vitro and in vivo. Sirt-1, an NAD+ dependent deacetylase, regulates a variety of cellular processes, including aging, lifespan extension and glucose and lipid metabolism. Herein, we applied a cellular steatosis model to investigate whether rapamycin's role in lipid metabolism is sirt 1-associated. Cells were exposed to palmitate stimulation for 48 h with or without rapamycin treatment. Lipid droplets in AML12 cells were observed by oil red O staining, and the intracellular lipid content was measured. We found that rapamycin treatment, at a relatively low concentration, significantly attenuated lipid aggregation, whereas knockdown of sirt-1 by siRNA abrogated rapamycin's effect on ameliorating lipid accumulation. Moreover, rapamycin exposure increased the expression levels of sirt-1 and AMPK, and enhanced sirt-1 deacetylase activity in steatotic AML12 hepatocytes. This is the first report demonstrating that rapamycin ameliorates lipid accumulation through upregulating sirt-1 signaling supporting the hypothesis that rapamycin may positively influence sirt-1 signaling in maintaining metabolic homeostasis.
雷帕霉素（Rap）是mTOR信号通路的特异性抑制剂，已被证明在体外和体内均可影响脂质代谢。Sirt-1是一种依赖NAD+的脱乙酰酶，可调节多种细胞过程，包括衰老、寿命延长以及葡萄糖和脂质代谢。在此，我们应用细胞脂肪变性模型来研究雷帕霉素在脂质代谢中的作用是否与Sirt-1相关。将细胞在有或无雷帕霉素处理的情况下暴露于棕榈酸刺激48小时。通过油红O染色观察AML12细胞中的脂滴，并测量细胞内脂质含量。我们发现，相对低浓度的雷帕霉素处理可显著减轻脂质聚集，而通过siRNA敲低Sirt-1可消除雷帕霉素对改善脂质积累的作用。此外，雷帕霉素处理可增加脂肪变性的AML12肝细胞中Sirt-1和AMPK的表达水平，并增强Sirt-1脱乙酰酶活性。这是第一份证明雷帕霉素通过上调Sirt-1信号通路改善脂质积累的报告，支持了雷帕霉素可能在维持代谢稳态中对Sirt-1信号通路产生积极影响的假设。
