Abstract: As the main bioactive component in pepper, piperine (1-piperoylpiperidine, PIP) has been shown to have a modulating effect on lipid metabolism and obesity. It has been reported that the circadian clock system is involved in the key steps of lipid synthesis and degradation, which maintains lipid homeostasis inside the body. Therefore, regulating the circadian system has become an important strategy in preventing lipid metabolism disorder. In this study, an obese rat model induced by a high-fat diet (HFD) was used to investigate the modulating effect of PIP on circadian misalignment caused by metabolic dysregulation. The results showed that PIP attenuated HFD-induced liver damage and lipid disorders, alleviated the circadian rhythm disruption of hepatic clock genes and lipid metabolism-associated genes, and restored the expression levels of lysobisphosphatidic acids (LBPA) (16:0_18:1), bis-methyl phosphatidic acid (BisMePA) (38:8e), phosphatidyl ethanolamine (PE) (16:0p_22:6) and methylphosphocholine (MePC) (32:4e), which are closely associated with circadian rhythm gene expressions. These findings may provide an important theoretical basis for PIP in regulating circadian rhythms of hepatic lipid metabolism.

Key words: Piperine, obese rats, lipid metabolism, circadian rhythm