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Amelioration of Alcoholic Liver Steatosis by Dihydroquercetin through the Modulation of AMPK-Dependent Lipogenesis Mediated by P2X7R–NLRP3-Inflammasome Activation

Author:
Zhang, Yu, Jin, Quan, Li, Xia, Jiang, Min, Cui, Ben-Wen, Xia, Kai-Li, Wu, Yan-Ling, Lian, Li-Hua, Nan, Ji-Xing
Source:
Journal of agricultural and food chemistry 2018 v.66 no.19 pp. 4862-4871
ISSN:
1520-5118
Subject:
Pseudotsuga menziesii, Silybum marianum, adenosine triphosphate, bark, caspase-1, ethanol, fatty liver, human cell lines, interleukin-1beta, lipid peroxidation, lipids, lipogenesis, mice, models, onions, phosphorylation, taxifolin, therapeutics
Abstract:
Dihydroquercetin (TAX) is the most abundant dihydroflavone found in onions, milk thistle, and Douglas fir bark. We investigated whether TAX could inhibit lipid accumulation in alcoholic liver steatosis in vivo and in vitro. An in vivo model was established by intragastrically treating mice with ethanol, and an in vitro model was created by treating HepG2 cells with ethanol. TAX regulated SREBP1 and ACC expression by elevating LKB1 and AMPK phosphorylation. Also, TAX upregulated SIRT1 expression, which was suppressed by ethanol intake. Decreased expression of P2X7R and NLRP3 and suppressed cleavage of caspase-1 by TAX resulted in the inhibition of IL-1β production and release. Additionally, TAX reduced lipogenesis and promoted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cells. TAX downregulated IL-1β cleavage responses to LPS and ATP stimulation in HepG2 cells. P2X7R deficiency attenuated lipid accumulation, characterized by increased AMPK activity and decreased SREBP1 expression in ethanol-treated HepG2 cells. Our data showed that TAX exhibited the ability to inhibit lipogenesis and a hepatoprotective capacity, indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.
Agid:
6042782