Theabrownin ameliorated lipid accumulation via modulating circadian rhythms in oleic acid-induced HepG2 cells

Theabrownin (TB) is the main characteristic component and bioactive substance of Pu-erh tea. Our previous studies have demonstrated interactions among the TB, the circadian rhythm, and obesity, but the underlying mechanism remains unclear. In this study, we focused on the mechanism by which TB ameliorates lipid accumulation caused by oleic acid (OA) by modulating circadian rhythm genes in HepG2 cells. The results showed that TB could reduce triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels, reactive oxygen species (ROS) overproduction and lipid droplet formation. Additionally, TB could regulate OA-mediated circadian desynchrony by regulating the mRNA and protein expression of circadian genes. Furthermore, as revealed by proteomics results, the PPAR pathway is a potential pathway through which TB ameliorates lipid metabolism disorders. After Bmal1 knockdown, the ameliorative effect of TB on OA-induced PPARγ and plin1 protein expression was decreased, which suggested that TB could ameliorate lipid accumulation in HepG2 cells via a Bmal1-dependent pathway.