Cichoric Acid Prevents Free-Fatty-Acid-Induced Lipid Metabolism Disorders via Regulating Bmal1 in HepG2 Cells

Cichoric acid (CA), a polyphenol component from Echinacea purpurea, exhibits preventive effects on liver lipid metabolism disorders in obesity. This research aimed to determine the role of circadian rhythm signaling during the process of CA-attenuated lipid accumulation in hepatocytes. In the current study, CA treatments improved cell morphology changes and hepatic lipid levels, which were triggered by free fatty acids (2:1, oleate: palmitate) in a dose-dependent way. Besides, CA (200 mu M) regulated the circadian rhythm expressions of clock genes and the relatively shallow daily oscillations. Moreover, silencing Bmall significantly blocked the p-Akt/Akt pathway to 80.1% +/- 1.5% and the p-GSK3 beta/GSK3 beta pathway to 64.7% +/- 2.8% (p < 0.05). Furthermore, silencing Bmall elevated the expressions of FAS and ACC to 122.4% +/- 5.6% and 114.9% +/- 1.7% in protein levels (p < 0.05) and to 166.5% +/- 18.S% and 131.4% +/- 5.5% in mRNA levels (p < 0.05). Therefore, our results demonstrated that CA has a Bmall resistance to lipid accumulation by enhancing the Akt/GSK3 beta signaling pathways and modulating the downstream expressions related to lipid metabolism, which indicated that CA might be useful as a natural and promising nonalcoholic fatty liver diseases (NAFLD) modulator.