Stearic acid reduces gene expression in FHs 74 Int and HepG2 cells

Abstract

Dietary stearic acid (18:0), in contrast to other saturated fatty acids, has cholesterol-lowering or neutral effects on plasma LDL and liver cholesterol concentration. Several mechanisms of action have been suggested, including reduced cholesterol absorption, increased bile acid excretion, and increased endogenous cholesterol excretion. We therefore hypothesized that several regulatory genes in liver and small intestine may be responsive to 18:0. Using human intestinal cell line FHs 74 Int and liver-derived HepG2 cells, we measured gene expression of Niemann-Pick C1-Like 1 (NPC1L1), HMG-CoA reductase (HMGR), acyl-CoA:cholesterol acyltransferase (ACAT2), ABCG5 sterol transporter (ABCG5), and LDL receptor (LDLR). Cells were incubated 24 h with 100 μM of 18:0 or palmitic acid (16:0) complexed to BSA, and mRNA was quantified by real time PCR. Results indicate: these genes are responsive to fatty acids in both FHs 74 Int and HepG2 cells, FHs 74 Int cells treated with 18:0 relative to 16:0 had significantly lower NPC1L1, HMGR, ABCG5 and ACAT2 gene expression, HepG2 cells treated with 18:0 relative to 16:0 had significantly lower HMGR gene expression. We conclude that the hypocholesterolemic effects of 18:0 are due to its ability to down-regulate genes involved in cholesterol transport and synthesis. (Supported by NSF EPSCoR grant EPS-0346476)