Dietary flavones counteract 5'-adenosine monophosphate-activated protein kinase-independent steroid response element binding protein-2 processing in cultured hepatocytes

Abstract

Consumption of fruits and vegetables is generally regarded as beneficial to plasma lipid profile. The mechanism by which the plant foods induce desirable lipid changes remains unclear. Steroid response element binding protein-2 (SREBP-2) is a crucial in cholesterol metabolism, and it is a major regulator of the cholesterol biosynthesis enzyme HMG CoA reductase (HMGCR). Our lab has previously illustrated that apigenin[1] and luteolin[2] could attenuate the nuclear translocation of SREBP-2 through an adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. In the present study, these two flavones were studied for their ability to deter the same in an AMPK-independent signaling route. The processing of SREBP-2 protein was promoted by phorbol 12-myristate 13-acetate (PMA) in the hepatic cells WRL and HepG2, and the increased processing was reversed by apigenin or luteolin co-administration. Electromobility shift assay results demonstrated that the PMA-induced DNA-binding activity was weakened by the flavones. The increased amount of nuclear SREBP-2 in cells was attenuated by the flavonoid as shown by immunocytochemical imaging. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that the transcription of HMGCR under both flavone treatments was reduced. However, apigenin appeared to be stronger than luteolin in restraining PMA-induced HMGCR mRNA expression. Because PMA is a diacylglycerol (DAG) analogue, these findings might have significant implications on conditions like overeating and obesity, leading to hepatic accumulation of DAG.