Diet‐induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress
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J. Neurochem. (2011) 118, 611–615. 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.
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Statin drugs likely alter brain cholesterol through indirect effects of altered systemic lipid metabolism.
“The precise mechanisms by which statin drugs alter brain cholesterol are unknown, but likely include indirect effects of altered systemic lipid metabolism48,49.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [49]
The Abstract reports that diet-induced elevations in peripheral cholesterol in rats accompanied increased hippocampal cholesterol, suggesting crosstalk between systemic and brain lipid metabolism. It does not study statin drugs or establish that their effects on brain cholesterol occur indirectly through systemic lipid changes. (LLM, conf=0.84)
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- Authors
- Stranahan, A. M., Cutler, R. G., Button, C., Telljohann, R., & Mattson, M. P.
- Affiliations
- National Institute on Aging (US)
- National Institutes of Health (US)
- Corresponding author
- Stranahan, Alexis M.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2011-07
- Volume
- 118
- Issue
- 4
- Pages
- 611-615
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC3137681
- OpenAlex
- W1824724965
- Cited by
- 100
- References
- 1
- Citations by year
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- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (F32AG034818)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- hippocampus, serum cholesterol, high-fat diet, saturated fat, sphingolipids, galactosylceramide, sphingomyelin, lipid peroxidation, oxidative stress, 4-hydroxynonenal, triglycerides, hyperlipidemia, neuroplasticity, brain lipid metabolism
- MeSH terms
- Aldehydes, Animals, Ceramides, Cholesterol, Cholesterol, Dietary, Diet, Dietary Carbohydrates, Dietary Fats, Galactosylceramides, Hippocampus, Liver, Male, Neurons, Sphingomyelins, Triglycerides, Rats, Sprague-Dawley, Oxidative Stress, Spectrometry, Mass, Electrospray Ionization, Lipid Metabolism, Rats
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