Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ɛ3 and ɛ4 knock-in mice

• Published in: Neurobiology of aging Vol. 34; no. 9; pp. 2217 - 2224
• Main Authors: Lim, Wei Ling Florence, Lam, Sin Man, Shui, Guanghou, Mondal, Alinda, Ong, Daniel, Duan, Xinrui, Creegan, Rhona, Martins, Ian J, Sharman, Matthew J, Taddei, Kevin, Verdile, Giuseppe, Wenk, Markus R, Martins, Ralph Nigel
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2013
• Subjects: Aging; APOE KI mice; Glycerophospholipids; High cholesterol; High fat; Internal Medicine; Mass spectrometry; Neurology; Oxysterols; APOE KI mice; High fat; Mass spectrometry; Glycerophospholipids; High cholesterol; Oxysterols
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2013.03.012

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 ɛ3 and ɛ4 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 ɛ4 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.