title: Differential regulation of cholesterol homeostasis in transgenic mice expressing human cholesterol ester transfer protein.
abstract: We investigated whether expression of cholesterol ester transfer protein (CETP) in mice alters the regulation of cholesterol metabolism. Transgenic mice expressing human CETP (CETP-TG) and nontransgenic littermates (non-TG) were fed either a monounsaturated fatty acid (MUFA) or a saturated fatty acid (SFA)-rich diet in the presence or absence of cholesterol. Mice fed with MUFA diet had higher CETP activity compared with SFA-fed mice. Addition of cholesterol to the MUFA diet decreased CETP activity, whereas addition of cholesterol to the SFA diet had no effect. Cholesterol 7alpha-hydroxylase (Cyp7a) activity was higher in CETP-TG mice compared with non-TG mice when fed a MUFA diet, whereas SFA fed CETP-TG mice showed lower Cyp7a activity as compared with non-TG. Microsomal triglyceride transfer protein (MTTP) activity was higher in CETP-TG mice compared with non-TG mice when fed a MUFA diet. HMG-CoA reductase activity was lower in CETP-TG mice compared with non-TG mice when fed a MUFA or a SFA diet. These data demonstrate that the regulation of Cyp7a, HMG-CoA reductase, and MTTP is altered in CETP-TG mice as compared with non-TG mice and these alterations are further modulated by the quality of dietary fats. These findings highlight the importance of CETP in regulating cholesterol homeostasis.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: Alka
authors.initials: A
authors.lastname: Agarwal-Mawal
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Murray
authors.forename: Suresh
authors.initials: S
authors.lastname: Belkhode
authors.forename: Sukhinder Kaur
authors.initials: SK
authors.lastname: Cheema
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood* / Q000235:genetics*; D004041:Dietary Fats / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology
chemical_list: D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004041:Dietary Fats; D008055:Lipids; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase