High-dose supplemental selenite to male Syrian hamsters fed hypercholesterolaemic diets alters Ldlr , Abcg8 and Npc1l1 mRNA expression and lowers plasma cholesterol concentrations

AbstractThe aim of the present study was to elucidate possible cholesterol-lowering mechanism(s) of high-dose supplemental Se in the form ofselenite, a known hypocholesterolaemic agent. Male Syrian hamsters (four groups, ten per group) were fed semi-purified diets for 4weeks containing 0·1% cholesterol and 15% saturated fat with selenite corresponding to varying levels of Se: (1) Se 0·15parts per million(ppm), control diet; (2) Se 0·85ppm; (3) Se 1·7ppm; (4) Se 3·4ppm. Lipids were measured in the bile, faeces, liver and plasma. The mRNAexpression of several known regulators of cholesterol homeostasis (ATP-binding cassette transporters g5 (Abcg5) and g8 (Abcg8),7-hydroxylase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, LDL receptor (LdLr) and Nieman-Pick C1-like 1 protein (Npc1l1)) weremeasured in the liver and/or jejunum. Oxysterols including 24-(S)-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol(27-OHC) were measured in the liver. Significantly lower total plasma cholesterol concentrations were observed in hamsters consumingthe low (0·85ppm) and high (3·4ppm) Se doses. The two highest doses of Se resulted in decreased plasma LDL-cholesterol concentrationsandincreasedmRNAlevelsofhepaticAbcg8,Ldlr andjejunalLdlr.Higherhepatic27-OHCandTAGconcentrationsandlowerlevelsofjejunalNpc1l1 mRNA expression were noted in the 1·7 and 3·4ppm Se-treated hamsters. Overall, Se-induced tissue changes in mRNA expressionincluding increased hepatic Abcg8 and Ldlr, increased jejunal Ldlr and decreased jejunal Npc1l1, provide further elucidation regarding thehypocholesterolaemic mechanisms of action of Se in the form of selenite.Key words: 27-Hydroxycholesterol: ATP binding cassette transporter g8: Niemann-pick C1-like 1 protein: Jejunum