Selective effect of dyslipidemic human sera on in vitro gene expression

Since serum lipids are affected by nutritional intake and endogenous metabolism, we assayed the ability of human sera, differing in several metabolic and nutritional parameters, to affect specific gene expression in human hepatoma cells using sera from hypercholesterolemic subjects (LDL-cholesterol median is 260mg/dl) vs normolipidemic subjects (LDL-cholesterol median is 160mg/dl).Hypercholesterolemic sera decreased sterol regulatory element binding protein 1c (SREBP-1c) mRNA by 40% (p<0.05). UDP-glucuronosyltransferase 1A1 (UGT1A1) mRNA expression was significantly increased by hypercholesterolemic sera by 84% (p<0.01).Determination of fatty acids levels in sera showed that arachidonic acid (AA) was 88% more abundant in high cholesterol subjects (p<0.01) while docosahexaneoic and eicosopentanoic acids (DHA and EPA), as quota of total detected fatty acids, were significantly higher in low cholesterol subjects by 25% (p<0.05) and by 80% (p<0.01) respectively. Higher DHA EPA and AA concentrations link to a 2 fold higher expression of UGT1A1.Although individual serum components accounting for the observed effects cannot be distinguished, our data indicate that the serum cholesterol containing lipoproteins directly affect gene expression pathways involved in metabolic regulation.This work was supported from the FARB 2007 and 2008 grants of the University of Salerno.