Abstract: Objective: This study investigated the regulatory effect of theabrownin (TB) from Pu-erh tea on lipid metabolism disorder induced by lipopolysaccharides (LPS) and its alleviating effect on metabolism-associated circadian rhythm disorders. Methods: SPF C57BL/6J mice were randomly divided into five groups: normal control, LPS model, low-dose TB (LTB), medium-dose TB (MTB), and high-dose TB (HTB). After completion of the intervention, the mice were slaughtered at zeitgeber time (ZT)0, ZT6, ZT12, ZT18, and ZT24. Enzyme-linked immunosorbent assay (ELISA) was used to detect blood lipids, liver lipids, serum hormones and liver injury indicators. The recovery from hepatic fibrosis and lipid droplet aggregation and accumulation were detected by hematoxylin-eosin (HE) staining and red O staining. The expression of genes and proteins linked to liver circadian rhythm were measured using real-time quantitative-polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Results: Compared with the normal control group, LPS treatment significantly increased the body mass and organ indices of mice as well as the activities of serum alanine aminotransferase (ALT) and aspartate transaminase (AST). LPS treatment was accompanied by lipid metabolism disorders and liver lipid metabolism disorders and changes in circadian rhythm. LPS treatment elevated serum endotoxin (ET) levels and caused abnormal secretion rhythm of melatonin (MT). LPS-induced pathological abnormalities were significantly reduced after TB intervention. Further analysis revealed that TB intervention alleviated LPS-induced lipid metabolism disorders, which was closely linked to the regulation of circadian rhythm-related gene and protein expression, such as circadian locomotor output cycle kaput (CLOCK), brain and muscle-Arnt-like protein 1 (BMAL1), and period circadian regulator 1 (PER1). Conclusion: TB can alleviate LPS-induced lipid metabolism disorders and further ameliorate the associated circadian rhythm disturbances in mice.

Key words: Pu-erh tea theabrownin; lipopolysaccharide; lipid metabolism disorders; circadian rhythm; liver