title: Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ε3 and ε4 knock-in mice.
abstract: Apolipoprotein E (ApoE) is important in facilitating the transport of lipids (cholesterol, phospholipids, and sulfatides) and plays a fundamental role in normal lipid metabolism. High cholesterol levels increases the risk of developing Alzheimer's disease. In this study, we investigated the effects of a high-fat high cholesterol (HFHC) diet on brain lipid profiles in 95 young and aged APOE ε3 and ε4 knock-in mice to determine whether diet leads to altered brain levels of a number of glycerophospholipids, sphingolipids, cholesterol precursors, cholesterol, cholesterol oxidation products, and cholesterol esters. The results in this study revealed significant changes in lipid levels. The HFHC-enriched diet influenced the levels of cholesterol esters. A sharp increase in cholesterol ester levels, particularly in the aged APOE ε4 diet-enriched group, might be suggestive of abnormal acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT) activity and/or levels. Age exerts appreciable effects on the brain lipidome, especially with regard to polar lipid species.
authors.affiliation: School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Nedlands, Australia.
authors.forename: Wei Ling Florence
authors.initials: WL
authors.lastname: Lim
authors.forename: Sin Man
authors.initials: SM
authors.lastname: Lam
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Alinda
authors.initials: A
authors.lastname: Mondal
authors.forename: Daniel
authors.initials: D
authors.lastname: Ong
authors.forename: Xinrui
authors.initials: X
authors.lastname: Duan
authors.forename: Rhona
authors.initials: R
authors.lastname: Creegan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Martins
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sharman
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Verdile
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Ralph Nigel
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics* / Q000502:physiology*; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D059305:Diet, High-Fat / Q000009:adverse effects*; D055879:Gene Knock-In Techniques; D005838:Genotype; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D013433:Sulfoglycosphingolipids; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1