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

Cellular and Molecular Neuroscience Section, Laboratory of Neurosciences, National Institute on Aging, Biomedical Research Center, Baltimore, Maryland, USA.
Journal of Neurochemistry (Impact Factor: 4.28). 06/2011; 118(4):611-5. DOI: 10.1111/j.1471-4159.2011.07351.x
Source: PubMed


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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Available from: Roy G Cutler, Jul 07, 2015
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    • "Lipid provides more energy value than carbohydrates because it contains more carbon and hydrogen atoms than carbohydrates but the dietary level of fat should not exceed 6 to 7% of dry matter (Doreau et al., 1997; Cooper, 2000). On the other hand, the serum lipid profile may be changed upon consumption of fat, and it is evidenced that serum cholesterol is directly related to lipid metabolism (Stranahan et al., 2011). "
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    ABSTRACT: The objective of the study was to investigate the effect of diets with inclusion of beef tallow on growth, carcass characteristics, meat quality and lipid profile of growing lambs. The experiment was conducted on 15 lambs for 63 days. The lambs were randomly allotted into three dietary treatments (T0, T1, and T2) with five animals in each group; T0 (control diet without beef tallow), T1 (diet with 2% beef tallow), and T2 (diet with 4% beef tallow). The body weight and feed conversion ratio (FCR) were significantly (P<0.05) increased in T1 group as compared to other groups. Dressing percentage of warm carcass in T0, T1 and T2 group was 43.93, 42.87 and 44.05%, respectively. There were no significant differences (P>0.05) on meat quality and chemical composition among the three dietary groups. Group T1 showed the highest increase of cholesterol concentration (11.5%) at the end of experiment but serum triglyceride concentration was not significantly (P>0.05) correlated with any of the three dietary groups. To sum up, the use of beef tallow at 2% level in lamb diet can increase their performance without having any deleterious effect on carcass, meat quality and lipid profile.
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    • "Though cholesterol cannot cross the BBB and dietary cholesterol does not directly affect the total levels of cholesterol and sulfatides in the brain (Darwish et al., 2010), cholesterol accumulation in the hippocampus is indeed promoted by both dietary cholesterol (Stranahan et al., 2011) and experience (Darwish et al., 2010). Therefore, the changes in hippocampal synaptic plasticity may not be directly modulated by hypercholesterolemia in cholesterol fed rabbits, but the gamut of modulators for LTP impairments in cholesterol fed rabbits could range from brain cholesterol metabolism (Darwish et al., 2010; Martin et al., 2014; Stranahan et al., 2011), accumulated beta-amyloid and senile plaque-like structures (Gengler et al., 2010; Sparks and Schreurs, 2003), down regulation of postsynaptic protein and dendritic spine-specific protein (Bhat and Thirumangalakudi, 2013) and dendritic microtubule associated protein (Freeman et al., 2011), alterations in dendrite morphology as shown in this manuscript, to synaptic ultrastructural changes in synapses of hippocampus Schaffer collateral pathway (Ya et al., 2013). Previous studies have shown that copper can affect both the sensitivity and the facilitation capability of hippocampal excitatory glutamatergic synapses (Gaier et al., 2014; Goldschmith et al., 2005; Peters et al., 2011) either directly by impaired copper homeostasis in the brain (Gaier et al., 2014; Goldschmith et al., 2005; Peters et al., 2011) or by increased beta amyloid accumulation (Sparks and Schreurs, 2003), therefore, copper may produce additive effect on these altered synaptic "
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    • "In addition, the single most important genetic risk factor for late-onset sporadic AD is the presence of the í µí¼€4 allele of the apolipoprotein E (apoE), the major brain lipoprotein, which mediates transport of cholesterol and other lipids [18] [19]. Epidemiological and animal studies suggested that a high-fat diet is a serious risk factor for the development of the disease, as it may elevate peripheral cholesterol, perturbate central lipid metabolism, and increase oxidative stress [20] [21] [22] [23] [24]. Among different lipid classes, ceramides have attracted much attention in recent years as key contributors in the pathology of AD as they are able to affect both Aí µí»½ generation and tau phosphorylation [25] [26]. "
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