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

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·2013·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2013.03.012
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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.

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  • In vitro, ACAT inhibition has cell-specific effects on ABCA1 and cholesterol efflux: it increases ABCA1 levels and cholesterol efflux in cholesterol-loaded macrophages, decreases ABCA1 levels in adipocytes, and decreases ABCA1 levels, lipid catabolism, and cholesterol efflux in APOE4 microglia.

    “In vitro, ACAT inhibition increases ABCA1 levels and cholesterol efflux of cholesterol-loaded macrophages, while decreasing ABCA1 levels in adipocytes [125] and decreasing ABCA1 levels, lipid catabolism, and cholesterol efflux in APOE4 microglia [126–128]”

    From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [126]

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Metadata

Authors
Lim, W. L. F., Lam, S. M., Shui, G., Mondal, A., Ong, D., Duan, X., Creegan, R., Martins, I. J., Sharman, M. J., Taddei, K., Verdile, G., Wenk, M. R., & Martins, R. N.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2013-09
Volume
34
Issue
9
Pages
2217-2224
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2013.03.012
Cited by
37
References
6
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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