Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ε3 and ε4 knock-in mice

Document Type

Journal Article




Faculty of Health, Engineering and Science


School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care



Grant Number

NHMRC Number : 595312


This article was originally published as: Wei Ling Florence Lim, Sin Man Lam, Guanghou Shui, Alinda Mondal, Daniel Ong, Xinrui Duan, Rhona Creegan, Ian J. Martins, Matthew J. Sharman, Kevin Taddei, Giuseppe Verdile, Markus R. Wenk, Ralph Nigel Martins, Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ɛ3 and ɛ4 knock-in mice, Neurobiology of Aging, Volume 34, Issue 9, September 2013, Pages 2217-2224. Original article available here.


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.



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Not open access