Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress

Alexis Michelle Stranahan, Roy G. Cutler, Catherine Button, Richard Telljohann, Mark P. Mattson

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)611-615
Number of pages5
JournalJournal of Neurochemistry
Volume118
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Oxidative stress
Nutrition
Lipid Metabolism
Oxidative Stress
Cholesterol
Diet
Serum
Hippocampus
Sphingolipids
Lipids
Metabolism
Brain
Triglycerides
Fats
Galactosylceramides
Computer peripheral equipment
Neuronal Plasticity
Sphingomyelins
Dietary Fats
High Fat Diet

Keywords

  • ceramide
  • cholesterol
  • high fat diet
  • hippocampus
  • sphingomyelin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress. / Stranahan, Alexis Michelle; Cutler, Roy G.; Button, Catherine; Telljohann, Richard; Mattson, Mark P.

In: Journal of Neurochemistry, Vol. 118, No. 4, 01.08.2011, p. 611-615.

Research output: Contribution to journalArticle

@article{207fd45d2b4a403bbbdd2fe3bf868160,
title = "Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress",
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.",
keywords = "ceramide, cholesterol, high fat diet, hippocampus, sphingomyelin",
author = "Stranahan, {Alexis Michelle} and Cutler, {Roy G.} and Catherine Button and Richard Telljohann and Mattson, {Mark P.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1111/j.1471-4159.2011.07351.x",
language = "English (US)",
volume = "118",
pages = "611--615",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress

AU - Stranahan, Alexis Michelle

AU - Cutler, Roy G.

AU - Button, Catherine

AU - Telljohann, Richard

AU - Mattson, Mark P.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

KW - ceramide

KW - cholesterol

KW - high fat diet

KW - hippocampus

KW - sphingomyelin

UR - http://www.scopus.com/inward/record.url?scp=79960563493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960563493&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2011.07351.x

DO - 10.1111/j.1471-4159.2011.07351.x

M3 - Article

C2 - 21682722

AN - SCOPUS:79960563493

VL - 118

SP - 611

EP - 615

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -