Apple polyphenol extract targets circadian rhythms to improve liver biological clock and lipid homeostasis in C57BL/6 male mice with mistimed high-fat diet feeding

Abstract

To investigate the potential role of apple polyphenol extract (APE) in the prevention and alleviation of circadian rhythm disturbances, eighty male C57BL/6 mice fed a high-fat diet (HFD) were randomized into four groups: 24 h ad libitum feeding (AL), 12 h restricted nighttime feeding (NF) or daytime feeding (DF), and daytime feeding with APE intragastric administration (DF-APE). Five weeks later, the mice were sacrificed at 6 h intervals over 24 h. Disrupted fluctuations in serum lipid profiles and hormones, along with desynchronization of circadian clock genes and metabolic genes were observed after daytime HFD feeding. However, APE treatment improved hepatic steatosis and recovered circadian rhythms of Cry1/2, and genes Acc and Hsl related to lipid synthesis and hydrolysis of cholesteryl esters, and Cyp7a1 in bile acid synthesis. In conclusion, the present study provides new evidence revealing that the circadian clock might be a novel target for APE to regulate metabolic homeostasis.

Keywords

• Apple polyphenol extract
• Bile acids metabolism
• Circadian rhythm
• Lipid metabolism
• Liver clock