Aims: The present study aims to detect the effect of
acanthoic acid (AA) on alcohol exposure-induced liver
lipid deposition and
inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of
ethanol (5 g/kg
body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last
ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay. AML-12 cells were pretreated with AA (5, 10, 20 μM), or
AICAR (500 μM),
GW3965 (1 μM),
SRT1720 (6 μM),
Nicotinamide (20 mM) for 2 h, respectively, and then following treated with EtOH (200 mM) and
lipopolysaccharide (LPS) (10 ng/ml) for additional 48 h. Cell
protein and
mRNA were collected for western blot and RT-PCR.
Cytokines interleukin-1β (IL-1β) and
tumor necrosis factor-α (TNF-α) release were detected by ELISA assay. Results: It was found that AA significantly decreased acute
ethanol-induced increasing of the serum ALT/AST, LDH, ALP levels, and hepatic and serum
triglyceride levels, and reduced fat droplets accumulation in mice liver. AA significantly suppressed the levels of
sterol regulatory element binding protein 1 (SREBP-1),
cytochrome P4502E1 (
CYP2E1), IL-1β, and caspase-1 induced by
ethanol. Furthermore, a significant decline of
sirtuin 1 (
Sirt1) and
liver X receptors (LXRs) levels was observed in EtOH group, compared with normal group mice. And AA pretreatment increased the
Sirt1 and LXRs levels, and also ameliorated phosphorylation of liver
kinase B-1 (LKB-1),
adenosine monophosphate-activated
protein kinase (AMPK),
acetyl CoA carboxylase (ACC)
proteins, compared with EtOH group. However, the levels of
peroxisome proliferator activated receptor -α or -γ (
PPAR-α or
PPAR-γ) induced by acute
ethanol were reversed by AA. In EtOH/LPS cultivated AML-12 cells, AA decreased IL-1β and TNF-α levels, lipid droplets, and SREBP-1 and
CYP2E1 expressions, compared with EtOH/LPS treatment. AA also significantly increased
protein expressions of
Sirt1, p-LKB1, p-ACC, PPARα, and decreased
protein expression of PPARγ, compared with EtOH/LPS treatment. Conclusion:
Acanthoic acid can partially prevent alcohol exposure-induced liver
lipid deposition and
inflammation via regulation of LKB1/
Sirt1/AMPK/ACC and LXRs pathways.