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

作者：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^*

来源：Journal of Pharmacy and Pharmacology, 2018, 70(3): 393-403.

DOI：10.1111/jphp.12877

• acanthoic acid
• alcoholic liver disease
• IRAK4
• lipin1
• 2
• lipopolysaccharide
• TLR4

ObjectivesIn 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.
MethodsHSC-T6 cells were treated with ethanol (200 mm) plus LPS (1 g/ml) for 1 h, followed by AA (10 or 20 m) 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 findingsAcanthoic acid significantly decreased the expressions of -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-B increased by EtOH/LPS on HSC cells. Results in vivo were consistent with results in vitro.
ConclusionsOur 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.

• 出版日期2018-3
• 单位延边大学