Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA.
Int J Mol Sci. 2022 May 17;23(10):5611. doi: 10.3390/ijms23105611.
Metabolic disorders are closely associated with the dysregulation of circadian rhythms. Many bioactive components with lipid metabolism-regulating effects have been reported to function through circadian clock-related mechanisms. As the main pungent principle of black pepper, piperine (PIP) has been demonstrated to possess anti-obesity bioactivity by affecting hepatic lipid metabolism-related factors. However, whether the circadian clock genes and are involved in the protective effect of PIP against lipid metabolism disorders remains unknown. In this work, oleic acid (OA) induced lipid accumulation in HepG2 cells. The effect of PIP on redox status, mitochondrial functions, and circadian rhythms of core clock genes were evaluated. Results revealed that PIP alleviated circadian desynchrony, ROS overproduction, and mitochondrial dysfunction. A mechanism study showed that PIP could activate the SREBP-1c/PPARγ and AMPK/AKT-mTOR signaling pathways in a /-dependent manner in HepG2 cells. These results indicated that and played important roles in the regulating effect of PIP on hepatic lipid homeostasis.
代谢紊乱与昼夜节律失调密切相关。许多具有调节脂质代谢作用的生物活性成分被报道通过与昼夜节律钟相关的机制发挥作用。胡椒碱（PIP）作为黑胡椒的主要辛辣成分，已被证明通过影响肝脏脂质代谢相关因素具有抗肥胖的生物活性。然而，昼夜节律钟基因 和 是否参与 PIP 对脂质代谢紊乱的保护作用尚不清楚。在这项工作中，油酸（OA）诱导 HepG2 细胞脂质积累。评估了 PIP 对氧化还原状态、线粒体功能和核心时钟基因昼夜节律的影响。结果表明，PIP 减轻了昼夜节律的失同步、ROS 产生过多和线粒体功能障碍。一项机制研究表明，PIP 可以在 HepG2 细胞中依赖 /-的方式激活 SREBP-1c/PPARγ 和 AMPK/AKT-mTOR 信号通路。这些结果表明 和 在 PIP 调节肝脂稳态的作用中发挥重要作用。
