title: Hepatic nuclear sterol regulatory binding element protein 2 abundance is decreased and that of ABCG5 increased in male hamsters fed plant sterols.
abstract: The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P < 0.0001), 60% (P < 0.0001), and 21% (P = 0.001), respectively, compared with controls. Furthermore, there was a 93% reduction (P < 0.0001) in hepatic total cholesterol and >6-fold (P = 0.029) and >2-fold (P < 0.0001) increases in hepatic beta-sitosterol and campesterol concentrations, respectively, in plant sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P < 0.03) and decreased cholesterol absorption 83% (P < 0.0001) compared with controls. Plant sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada R3T 6C5.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Harding
authors.forename: Todd C
authors.initials: TC
authors.lastname: Rideout
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Jones
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D013261:Sterols / Q000008:administration & dosage*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D001798:Blood Proteins; D008055:Lipids; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols