Acanthoic acid suppresses lipin1/2 via TLR4 and IRAK4 signalling pathways in EtOH‐ and lipopolysaccharide‐induced hepatic lipogenesis

Objectives In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH‐ and LPS‐induced hepatic lipogenesis. Methods HSC‐T6 cells were treated with ethano...

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Published in:Journal of pharmacy and pharmacology 2018-03, Vol.70 (3), p.393-403
Main Authors: Song, Jian, Han, Xin, Yao, You‐Li, Li, Ya‐Mei, Zhang, Jing, Shao, Dan‐Yang, Hou, Li‐Shuang, Fan, Ying, Song, Shun‐Zong, Lian, Li‐Hua, Nan, Ji‐Xing, Wu, Yan‐Ling
Format: Article
Language:English
Subjects:
acanthoic acid
Alcoholic beverages
alcoholic liver disease
Body weight
CD14 antigen
Collagen
Ethanol
Fibrosis
IRAK4
lipin1/2
Lipogenesis
lipopolysaccharide
Lipopolysaccharides
Liver
Liver diseases
Mice
NF-κB protein
Rodents
Signal transduction
Sterol regulatory element-binding protein
TAK1 protein
TLR4
TLR4 protein
Toll-like receptors
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Summary:Objectives In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH‐ and LPS‐induced hepatic lipogenesis. Methods HSC‐T6 cells were treated with ethanol (200 mm) plus LPS (1 μg/ml) for 1 h, followed by AA (10 or 20 μm) for another 6 h. C57BL/6 mice were pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Key findings Acanthoic acid significantly decreased the expressions of α‐SMA, collagen‐I, SREBP‐1, and lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p‐TAK1 and NF‐κB increased by EtOH/LPS on HSC cells. Results in vivo were consistent with results in vitro. Conclusions Our data demonstrated that AA might modulate hepatic fibrosis and lipid deposition in HSC‐T6 cell stimulated with ethanol combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways, and AA might be considered as a potential therapeutic candidate for alcoholic liver disease.
ISSN:0022-3573
2042-7158
DOI:10.1111/jphp.12877