Abstract 386: Dietary Oxidized Linoleic Acid Modulates PCSK9 and Associated Genes

Introduction: We have previously shown that oxidized linoleic acid (OxLA) modulate plasma lipids. In this study we investigated the role of dietary OxLA on PCSK-9 and its associated genes. Method: Liver tissue from four groups of normal C57BL6 mice were feed; plain chow, chow supplemented with linoleic acid (9mg), chow supplemented with a low concentration of OxLA (9mg) and chow supplemented with a high concentration of OxLA (18mg) were analyzed for PCSK-9 and related genes. RNA from these livers samples was extracted with Trizol, assessed for purity by agarose gel electrophoresis and quantified using fluorometry. cDNA was synthesized from total extracted RNA and subsequently used for qRT-PCR analysis. Gene expressions of PCSK-9, SREBP-1, HNF-1α and PPARα were measured and normalized to GAPDH . Total, free and cholesterol ester levels in the liver were analyzed spectrophotometrically. Experiments were performed in triplicates and the difference between means was determined using a student’s T-test with a p value of <0.05 accepted as statistically significant. Results: PCSK-9 gene expression was markedly elevated in the mice fed high concentration OxLA, SREBP-1 gene levels in these of mice was also significantly elevated in comparison to the other 3 groups which had relatively the same levels of SREBP-1 gene expression. Conversely HNF-1α gene expression levels were elevated in all groups except the mice on low concentration OxLA. PPARα gene levels were significantly down regulated in the mouse on high concentration OxLA. Plasma total cholesterol levels were significantly elevated in both groups on OxLA. Conclusion: Elevated cholesterol levels in the livers of mice fed high concentration OxLA was accompanied with increased PCSK-9 expression. These results show that OxLA modulate PCSK-9 and its associated genes expression and promote accumulation of liver cholesterol.