title: Dietary cholesterol-induced down-regulation of intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity is diminished in rabbits with hyperresponse of serum cholesterol to dietary cholesterol.
abstract: Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was twofold higher in the hyporesponders. The addition of cholesterol (3 g/kg) to the diet caused similar depression of hepatic HMG-CoA reductase activity in the two strains, whereas intestinal HMG-CoA reductase activity was significantly reduced in hyporesponders but not in hyperresponders. Cholesterol feeding induced higher free cholesterol concentrations in hepatic and intestinal microsomes of both hypo- and hyperresponders and higher activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). Hepatic ACAT activity was significantly lower in cholesterol-fed hyperresponders than in hyporesponders, which may have contributed to the observed higher free cholesterol concentrations in hepatic microsomes of cholesterol-fed hyperresponders. Intestinal ACAT activity was similar in hypo- and hyperresponders; cholesterol feeding tended (P = 0.11) to elevate the activity of this enzyme. Hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in cholesterol-fed hyperresponders than in hyporesponders; it was slightly depressed after cholesterol loading in both rabbit strains.
authors: Department of Laboratory Animal Science, University of Utrecht, The Netherlands.
authors: G W
authors: GW
authors: Meijer
authors: M J
authors: MJ
authors: Smit
authors: J G
authors: JG
authors: Van Der Palen
authors: F
authors: F
authors: Kuipers
authors: R J
authors: RJ
authors: Vonk
authors: B F
authors: BF
authors: Van Zutphen
authors: A C
authors: AC
authors: Beynen
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
chemical_list: D002791:Cholesterol, Dietary; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases