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Diet‐induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress
Author(s) -
Stranahan Alexis M.,
Cutler Roy G.,
Button Catherine,
Telljohann Richard,
Mattson Mark P.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07351.x
Subject(s) - endocrinology , medicine , sphingolipid , cholesterol , hippocampal formation , lipid metabolism , oxidative stress , triglyceride , hippocampus , sphingomyelin , ceramide , lipid peroxidation , biology , hyperlipidemia , chemistry , biochemistry , apoptosis , diabetes mellitus
J. Neurochem. (2011) 118 , 611–615. Abstract The structure and function of the hippocampus, a brain region critical for learning and memory, is impaired by obesity and hyperlipidemia. Peripheral cholesterol and sphingolipids increase progressively with aging and are associated with a range of age‐related diseases. However, the mechanisms linking peripheral cholesterol metabolism to hippocampal neuroplasticity remain poorly understood. To determine whether diets that elevate serum cholesterol influence lipid metabolism in the hippocampus, we maintained rats on a diet with high amounts of saturated fat and simple sugars for 3 months and then analyzed hippocampal lipid species using tandem mass spectrometry. The high fat diet was associated with increased serum and liver cholesterol and triglyceride levels, and also promoted cholesterol accumulation in the hippocampus. Increases in hippocampal cholesterol were associated with elevated galactosyl ceramide and sphingomyelin. To determine whether changes in lipid composition exerted biological effects, we measured levels of the lipid peroxidation products 4‐hydroxynonenal‐lysine and 4‐hydroxynonenal‐histidine; both were increased locally in the hippocampus, indicative of cell membrane‐associated oxidative stress. Taken together, these observations support the existence of a potentially pathogenic relationship between dietary fat intake, peripheral cholesterol and triglyceride levels, brain cell sphingolipid metabolism, and oxidative stress.