Excessive
lipid accumulation in the liver has been proposed to cause
hyperlipidemia, diabetes and
fatty liver disease.
4-Hydroxyderricin (4HD),
xanthoangelol (XAG),
cardamonin (CAR) and
flavokawain B (FKB) are
chalcones that have exhibited various biological effects against
obesity,
inflammation, and diabetes; however, little is known about the inhibitory effects of these
chalcones on
fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce
lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of
fatty acids (FAs;
palmitic acid :
oleic acid = 1 : 2 ratio), significant
lipid accumulation was observed. Under the same experimental conditions, addition of
chalcones at 5 μM significantly suppressed the FA-induced
lipid accumulation. We found that the expression of
sterol regulatory
element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these
chalcone-treated cells. We also found that these
chalcones increased the expression of
peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these
chalcones increased phosphorylation of
AMP-activated protein kinase (AMPK) and liver
kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an
AMPK inhibitor, compound C, reversed
chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated
lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells.