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

Jul 24, 2018Journal of agricultural and food chemistry

Cichoric Acid May Prevent Fat-Related Fat Metabolism Problems by Controlling a Key Body Clock Protein in Liver Cells

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Abstract

Cichoric acid (CA) treatments improved hepatic lipid levels in a dose-dependent manner.

CA is derived from Echinacea purpurea and may help prevent liver lipid-metabolism disorders associated with obesity.
The treatment improved cell morphology changes in hepatocytes triggered by free fatty acids.
CA regulated the daily expressions of clock genes, affecting circadian rhythm signaling.
Silencing the Bmal1 gene significantly reduced the activity of the p-Akt/Akt and p-GSK3β/GSK3β pathways.
Silencing Bmal1 increased protein and mRNA levels of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC).
CA may offer a natural approach to modulate nonalcoholic fatty liver diseases (NAFLD) through its effects on lipid metabolism.

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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 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.

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

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