Effects of niacin and chromium on the expression of ATP-binding cassette transporter A1 and apolipoprotein A-1 genes in HepG2 cells

Abstract

The ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein A1 (ApoA-1) are both involved in the regulation of cholesterol efflux from cells. The overexpression of ABCA1 and ApoA-1 genes are associated with increased high-density lipoprotein (HDL) levels. Previous studies have shown that niacin and chromium reduce plasma cholesterol while increasing HDL levels. The aim of the present study was to determine the effects of niacin and chromium on HDL formation by investigating the changes in ABCA1 and ApoA-1 transcription in the human hepatoblastoma cell line (HepG2 cells). Cells were treated with either niacin or chromium, or the combination of both. The expression of ABCA1 and ApoA-1 mRNA was measured by a relative quantitative real-time reverse transcriptase-polymerase chain reaction method. Results showed that niacin at concentrations of 1 and 5 mM significantly increased ABCA1 (1.3–1.7-fold), without affecting ApoA-1 (0.8–1.2-fold), whereas chromium at 3 mM significantly increased both ABCA1 (1.7±0.01-fold) and ApoA-1 (1.5±0.1-fold) transcription when compared to untreated cells. Niacin and chromium cotreatment significantly induced the expression of peroxisome proliferator-activated receptor-α (PPARα) mRNA by approximately 1.3–1.8-fold. It was likely that the increases observed for the ABCA1 transcript may be regulated by the increases in PPARα transcription. A combination of niacin and chromium chloride did not significantly increase (3+1 mM) but instead reduced (1+3 mM) ABCA1 gene expression. In the case of ApoA gene, the combination of niacin and chromium chloride at concentrations of 1+3 mM significantly elevated expression; however, this effect was not observed at concentrations of 3+1 mM. When cells were treated with the combination at both concentrations, only slight increases in PPARα mRNA was observed. Niacin, but not chromium, significantly reduced intracellular cholesterol. We hypothesize that the stimulation of ABCA1 gene expression causes an enhanced cholesterol efflux, perhaps mediated by PPARα pathway(s).