Fatty acids stimulate lipid accumulation in parallel with increased expression of adipose differentiation -related protein (ADRP) in liver cells. Although it is generally considered that the fatty acid effect on ADRP expression is mediated by PPARs, we identified here an additional molecular mechanism using NMuLi mouse liver non-parenchymal cell line which expresses PPAR and , but not . Oleic acid (OA) and specific ligands for PPARand stimulated ADRP expression as well as the -2090bp ADRP promoter activity which encompasses the PPAR response element (PPRE) adjacent to an Ets/AP-1 site. When the AP-1 site was mutated, OA failed to stimulate the activity despite the presence of the PPRE, while ligands for PPARanddid stimulate it and so did a PPAR ligand under the co-expression of PPAR. DNA binding of AP-1 was stimulated by OA, but not by PPAR ligands. Since we previously demonstrated that Pycnogenol (PYC), a French maritime pine bark extract, suppressed ADRP expression in macrophages partly by suppression of AP-1 activity, we tested the effect of PYC on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression of lipid droplet formation. However, PYC neither suppressed the OA-stimulated ADRP promoter activity nor DNA binding of AP-1, but instead, reduced the ADRP mRNA half-life. All these results indicate that the effect of OA on ADRP expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression in part by facilitating mRNA degradation. PYC, a widely used dietary supplement, could be beneficial for the prevention of excessive lipid accumulation such as hepatic steatosis.