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Cichoric Acid Prevents Free-Fatty-Acid-Induced Lipid Metabolism Disorders via Regulating Bmal1 in HepG2 Cells
journal contribution
posted on 2018-07-23, 00:00 authored by Rui Guo, Beita Zhao, Yijie Wang, Dandan Wu, Yutang Wang, Yafan Yu, Yuchen Yan, Wentong Zhang, Zhigang Liu, Xuebo LiuCichoric
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 μM) regulated
the circadian rhythm expressions of clock genes and the relatively
shallow daily oscillations. Moreover, silencing Bmal1 significantly blocked the p-Akt/Akt pathway to 80.1% ± 1.5%
and the p-GSK3β/GSK3β pathway to 64.7% ± 2.8% (p < 0.05). Furthermore, silencing Bmal1 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% ± 18.5% and 131.4% ± 5.5% in mRNA levels (p < 0.05). Therefore, our results demonstrated that CA
has a Bmal1 resistance to lipid accumulation by enhancing
the Akt/GSK3β 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.