Cholesterol Journal Articles

Record 1461 to 1480

Brain cholesterol, statins and Alzheimer's Disease
Kirsch, C., G. P. Eckert, et al. (2003), Pharmacopsychiatry 36 Suppl 2: S113-9.
Abstract: Growing evidence suggests that cellular cholesterol homeostasis is causally involved in different steps leading to pathological events in the brain of Alzheimer's Disease (AD) patients. It was previously demonstrated that the processing of the amyloid beta-peptide precursor protein (APP) is modulated by pronounced alterations in cellular cholesterol levels using statins or cholesterol extracting agents. However, a cholesterol-rich diet was found to enhance amyloid beta-peptide (Abeta) burden in the brain of transgenic mice without clearly affecting total brain cholesterol levels. Recent retrospective epidemiological studies have reported that the use of statins potentially suppresses the development of AD. Although some HMG-CoA reductase inhibitors seem to influence the central cholesterol pool in vivo, the above epidemiological findings are probably not linked to statin-induced changes in brain membrane cholesterol levels per se since not all statins active in preventing AD enter the central nervous system (CNS). Recently, we reported that different statins, regardless of their brain availability, induce alterations in cellular cholesterol distribution in the brain. Such pleiotropic, cholesterol-synthesis independent statin effects might be indirect and are possibly mediated at the blood-brain barrier (BBB) via nitric oxide (NO) or apolipoprotein E (ApoE).

Brain cholesterol: long secret life behind a barrier
Bjorkhem, I. and S. Meaney (2004), Arterioscler Thromb Vasc Biol 24(5): 806-15.
Abstract: Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier efficiently protecting it from exchange with lipoprotein cholesterol in the circulation. Thus, there is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Under steady-state conditions, most of the de novo synthesis of cholesterol in the brain appears to be balanced by excretion of the cytochrome P-450-generated oxysterol 24S-hydroxycholesterol. This oxysterol is capable of escaping the recycling mechanism and traversing the blood-brain barrier. Cholesterol levels and cholesterol turnover are affected in neurodegenerating disorders, and the capacity for cholesterol transport and recycling in the brain seems to be of importance for the development of such diseases. The possibility has been discussed that administration of inhibitors of cholesterol synthesis may reduce the prevalence of Alzheimer disease. No firm conclusions can, however, be drawn from the studies presented thus far. In the present review, the most recent advances in our understanding of cholesterol turnover in the brain is discussed.

Brain does not utilize low density lipoprotein-cholesterol during fetal and neonatal development in the sheep
Turley, S. D., D. K. Burns, et al. (1996), J Lipid Res 37(9): 1953-61.
Abstract: Several lines of evidence have suggested that central nervous system development and function depend upon a supply of cholesterol that comes from low density lipoproteins (LDL-C). These studies test this hypothesis directly by measuring in vivo the uptake of LDL-C in nine regions of the central nervous system at five different stages of development in the fetal and neonatal sheep. The concentration of LDL-C in the plasma decreased from 49 mg/dl in the fetus 90 days before birth (-90 days) to only 10 mg/dl at -13 days. By 17 days postnatal this value increased to nearly 60 mg/dl. Throughout the period of development between -90 days (very early fetus) and 17 days (late neonatal animal) the weight of the brain increased 32-fold (from 2.3 to 73.6 g) and the content of cholesterol rose 100-fold (from 8.6 to 876 mg), yet there was no detectable LDL-C uptake in any of nine areas of the central nervous system at any stage of development (clearances of < 2 microliters/h per g). This was true even in the -90 day fetus prior to closure of the blood brain barrier. In contrast, LDL-C clearance by the adrenal gland increased dramatically (from 91 to 348 microliters/h per g) as it also did in the liver (from 36 to 85 microliters/h per g) during fetal development. These studies strongly suggest, therefore, that cholesterol carried in LDL plays little or no role in the process of sterol acquisition during brain development or in cholesterol turnover in the mature central nervous system. Changes in circulating LDL-C concentration, therefore, should have no effect on brain function.

Brain in human nutrition and variant Creutzfeldt-Jakob disease risk (vCJD): detection of brain in retail liver sausages using cholesterol and neuron specific enolase (NSE) as markers
Lucker, E., S. Horlacher, et al. (2001), Br J Nutr 86 Suppl 1: S115-9.
Abstract: No information is available about the consumption of brain via meat products. With respect to the new variant of Creutzfeldt-Jakob disease (vCJD) and the presumed food-borne transmission of bovine spongiform encephalopathy (BSE) to humans, a preliminary survey for brain and/or spinal cord (tissues of the central nervous system, CNS) was conducted. We applied a previously developed integrated procedure using cholesterol and neuron specific enolase (NSE) as markers. Quantification of cholesterol had to be backed up by NSE immunochemistry in order to account for low specificity and relatively high variances. Out of 126 high-quality finely graded liver sausages, five samples (4 %) showed positive NSE immunoresponses. In four of these samples a transgression of the normal maximum cholesterol content was obtained. The identification of such a considerable number of CNS-positive sausages indicates that brain consumption is not as rare as previously assumed. Overall, the present integrated method could be successfully applied for the detection of CNS in heat-treated meat products. Its routine application in official food control would deter illegal practice and thus help to control transmissible spongiform encephalopathies.

Brain membrane cholesterol domains, aging and amyloid beta-peptides
Wood, W. G., F. Schroeder, et al. (2002), Neurobiol Aging 23(5): 685-94.
Abstract: Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. These domains consist of the exofacial and cytofacial leaflets, cholesterol pools, annular lipids, and lipid rafts. Membrane lipid domains have been proposed to be involved in a variety of different functions including e.g. signal transduction, lipid transport and metabolism, and cell growth. Membrane lipid domains have been identified in brain and can be modified by different experimental conditions, aging and certain neurodegenerative diseases. Recent data reveal the very interesting possibility that membrane lipid domains may be a target of Alzheimer's disease. There is a growing body of evidence showing an association between cholesterol and Alzheimer's disease, and cholesterol is a major component of membrane lipid domains. Here we discuss recent data on brain membrane lipid domains emphasizing the structural and functional role of cholesterol. In addition, lipid domains and aging, and the potential interaction of lipid domains and amyloid beta-peptides (Abeta) that are a major component of senile plaques in brains of Alzheimer's patients are considered. We propose that age changes in the asymmetric distribution of cholesterol in contrast to total or bulk cholesterol in neuronal plasma membranes provides a cooperative environment for accumulation of Abeta in plasma membranes and the accumulation of Abeta is due in part to a direct physico-chemical interaction with cholesterol in the membrane exofacial or outer leaflet.

Brain Na+ K+ ATPase and cholesterol in acute experimental trypanosomiasis
Nok, A. J., K. A. Esievo, et al. (1992), Cell Biochem Funct 10(4): 233-6.
Abstract: Brain Na+ K+ ATPase activity has been found to decrease in experimental trypanosomiasis in rats infected with Trypanosoma congolense. Some physical features that affect membrane fluidity were also observed to be altered. The levels of cholesterol in the brain and free fatty acids in the serum were found to increase in the infected animals. These findings might be relevant to the development of brain lesions.

Brain-membrane cholesterol in Alzheimer's disease
Eckert, G. P., C. Kirsch, et al. (2003), J Nutr Health Aging 7(1): 18-23.
Abstract: Cholesterol represents an important determinant of the physical state of biological membranes. Growing evidence indicate that changes in brain cholesterol and variations in neuronal membrane structure are involved in the development of Alzheimer's disease (AD). Cholesterol modulates the cleavage of the amyloid precursor protein and thus affect cellular production of beta-amyloid peptides (Ab). On the other hand, cholesterol seems to be protective against the neurotoxic and membrane disordering properties of Ab. Present review summarizes reports focusing on brain membrane changes in AD and the effects of Ab on these structures. Since it has been shown that these Ab effects are cholesterol dependent, recent findings are presented indicating that the modulation of membrane cholesterol refers to different cholesterol pools within the membranes. Further, consequences thereof for possible pharmacological strategies are discussed.

Bran fibers and cholesterol concentration in rats
Mongeau, R. (1994), J Nutr 124(10): 2039-40.

Branched phosphatidylcholines stimulate activity of cytochrome P450SCC (CYP11A1) in phospholipid vesicles by enhancing cholesterol binding, membrane incorporation, and protein exchange
Kisselev, P., R. Wessel, et al. (1998), J Biol Chem 273(3): 1380-6.
Abstract: Phosphatidylcholines (PCs) with branched fatty acyl chains substituted in the two positions of the main chains (branched PCs) have been shown to be potent activators of the side chain cleavage activity of cytochrome P450SCC (CYP11A1) (Schwarz, D., Kisselev, P., Wessel, R., Jueptner, O., and Schmid, R. D. (1996) J. Biol. Chem. 271, 12840-12846). The present study reports on the effect of a series of branched PC on cholesterol binding, membrane integration, and protein exchange in large unilamellar vesicles prepared by an extrusion technique. Enzyme kinetics using vesicles as well as optical titration using a micelle system with the detergent Tween 20 demonstrate that activation is correlated with the fraction of P450SCC in the high spin form. The potency of branched PCs both to activate the enzyme and to induce spin state changes increases with increasing lengths of both the branched and main fatty acyl chains. We found that the extent as well as the rate of integration of P450SCC into vesicle membranes studied by gel chromatography and stopped flow kinetics were increased by branched PC. Finally, it is demonstrated by measurement of the enzymatic activity in primary and secondary vesicles that branched PCs are potent in retaining a very rapid exchange of P450SCC between vesicles, in contrast to cardiolipin, that partially inhibits this exchange process. The data suggest that different properties of P450SCC in membrane systems including cholesterol binding, membrane integration, and protein exchange are affected by branched PCs and probably by other phospholipids, too, and therefore must be considered in an explanation of the observed high stimulation of activity.

Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins
Grunler, J., J. Ericsson, et al. (1994), Biochim Biophys Acta 1212(3): 259-77.

Brefeldin A (BFA) inhibits basolateral membrane (BLM) delivery and dimerization of transcobalamin II receptor in human intestinal epithelial Caco-2 cells. BFA effects on BLM cholesterol content
Bose, S., S. J. Chapin, et al. (1998), J Biol Chem 273(26): 16163-9.
Abstract: Brefeldin A (BFA) treatment of Caco-2 cells (5 microg/ml for 12 h) reduced by 90% the cholesterol, but not the phospholipid (PL), levels of the basolateral membrane (BLM), thus altering its PL/cholesterol molar ratio from 2.6 to 22.0, and decreasing its steady state fluorescent anisotropy (rs) from 0.27 to 0.15. BFA treatment for 12 h also resulted in complete loss of transcobalamin II receptor (TC II-R) activity/protein levels in the BLM and the disappearance of trans-Golgi network (TGN) morphology as revealed by confocal immunofluorescence microscopy using antibody to TGN 38. However, BFA treatment had no effect on either total cellular cholesterol, TC II-R activity, or PL levels. When cells treated with BFA for 12 h were exposed to BFA-free medium for 0-24 h, all of the effects were reversed, including reappearance of normal TGN morphology. TC II-R delivered to the BLM during this period was progressively sialylated and changed its physical state from a monomer (8 h) to a dimer (12 h), coinciding with increased delivery (11-53 pmol) of cholesterol to the BLM and an increase in the BLM rs from 0.15 to 0.21. These results indicate that cholesterol, but not PL, delivery to the BLM of Caco-2 cells is BFA-sensitive, and cholesterol, by influencing the higher order of the BLM, is essential for TC II-R dimerization.

Bringing the cholesterol message to the public: dietitians must be proactive in nutrition counseling
Yetiv, J. Z. and A. M. Del Tredici (1990), J Am Diet Assoc 90(10): 1383-6.

Brisk walking and high density lipoprotein cholesterol
Bain, S. C. and A. F. Jones (1990), Bmj 300(6718): 195-6.

Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain
Mast, N., R. Norcross, et al. (2003), Biochemistry 42(48): 14284-92.
Abstract: The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol. This reaction produces biologically active oxysterol, 24(S)-hydroxycholesterol, and is also the first step in enzymatic degradation of cholesterol in the brain. We report here that P450 46A1 can further metabolize 24(S)-hydroxycholesterol, giving 24,25- and 24,27-dihydroxycholesterols in both the cell cultures transfected with P450 46A1 cDNA and the in vitro reconstituted system with recombinant enzyme. In addition, P450 46A1 was able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone). Also, P450 46A1 was found to metabolize xenobiotics carrying out dextromethorphan O- and N-demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation. Thus, substrate specificities of P450 46A1 are not limited to cholesterol and include a number of structurally diverse compounds. Activities of P450 46A1 suggest that, in addition to the involvement in cholesterol homeostasis in the brain, this enzyme may participate in metabolism of neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system.

Budget fat to control cholesterol
Rasmussen, J. (1991), Nebr Nurse 24(1): 35.

Building up of the liquid-ordered phase formed by sphingomyelin and cholesterol
Chachaty, C., D. Rainteau, et al. (2005), Biophys J 88(6): 4032-44.
Abstract: The long-range and molecular orders and dynamics in codispersions of egg sphingomyelin-cholesterol have been investigated by synchrotron x-ray diffraction and electron spin resonance using phosphatidylcholine spin-labeled at several positions on the sn-2 chain. Mixtures containing 0, 17, 33, 41, 50 mol% cholesterol exhibited a single phase by x-ray diffraction methods. The temperature dependence of the d-spacing between 20 and 50 degrees C is attenuated with increasing proportions of cholesterol, becoming invariant for cholesterol contents of 41 and 50 mol% on completion of the liquid-ordered phase. Electron spin resonance revealed two sites for 17 and 33 mol% cholesterol. One site is highly ordered and the other is less ordered than the fluid phase of pure sphingomyelin as shown by the molecular and the intramolecular order parameters reflecting the segmental motions of the probe. The two-sites exchange rate indicates a mean lifetime of the sites of approximately 0.1 micros during which the lipid displacement is approximately 1 nm. The short lifetime of the sites probed by ESR and the single phase detected by x-ray diffraction support in this binary mixture, the building up of the Lo phase by a progressive accumulation of randomly distributed sphingomyelin-cholesterol condensed complexes rather than by diffusional exchange between extended domains.

Butter and total cholesterol
Immich, H. (1993), Versicherungsmedizin 45(6): 195-7.
Abstract: This paper gives reasons for the following statements: 1. Restricted consumption of butter does not influence the physiological cholesterol levels. 2. An association between high cholesterol levels and the incidence of coronary sclerosis can not be demonstrated. 3. Hitherto all intervention trials do not show any effect. 4. No longer serum cholesterol can be considered as a factor of risk.

Butter naturally enriched in conjugated linoleic acid and vaccenic acid alters tissue fatty acids and improves the plasma lipoprotein profile in cholesterol-fed hamsters
Lock, A. L., C. A. Horne, et al. (2005), J Nutr 135(8): 1934-9.
Abstract: Butter, which is naturally enriched in cis-9, trans-11 conjugated linoleic acid (rumenic acid; RA) and vaccenic acid (VA), has been shown to be an effective anticarcinogen in studies with animal models; however, there has been no examination of the effects of a naturally derived source of VA and RA on atherosclerosis-related biomarkers. The current study was designed to determine the effect of a diet containing VA/RA-enriched butter on plasma lipoproteins and tissue fatty acid profiles in cholesterol-fed hamsters. Male Golden Syrian hamsters were fed diets containing 0.2% cholesterol and 20% added fat as: 1) Control, 20% standard butter (CT); 2) 5% standard butter + 15% VA/RA-enriched butter (EB); 3) 15% standard butter + 5% partially-hydrogenated vegetable oil (VO). After 4 wk, plasma lipoproteins were isolated, cholesterol quantified, and tissue fatty acid profiles determined. Tissue concentrations of VA and RA were increased by consumption of the EB diet compared with both the CT and VO diets, whereas the VO diet increased their concentration compared with the CT diet only. Total and LDL cholesterol concentrations were significantly reduced in hamsters fed EB and VO compared with CT, whereas VLDL cholesterol concentrations were reduced in hamsters fed EB compared with those fed CT and VO. HDL cholesterol concentrations did not differ among treatments. The ratio of potentially atherogenic lipoproteins VLDL + intermediate density lipoproteins (IDL) + LDL to antiatherogenic HDL was significantly lower in hamsters fed VA/RA-enriched butter (0.60) than in those fed either control diet (1.70) or the diet containing partially hydrogenated vegetable oil (1.04). Thus, increasing the VA/RA concentration of butter results in a plasma lipoprotein cholesterol profile that is associated with a reduced risk of atherosclerosis.

Butyrate stimulates ApoA-IV-containing lipoprotein secretion in differentiated Caco-2 cells: role in cholesterol efflux
Nazih, H., F. Nazih-Sanderson, et al. (2001), J Cell Biochem 83(2): 230-8.
Abstract: The aim of this study was to determine: (1) whether the Short Chain Fatty Acids (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of intestinal apolipoprotein A-IV-containing lipoproteins and (2) if so, whether these particles are able to promote cholesterol efflux in vitro. For this purpose Caco-2 cells were used for their functional properties of differentiated enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h. Only butyrate stimulated apoA-IV gene expression and this was associated with an increase in apoA-IV secretion. A nondenaturing 2D-PAGE (agarose gel was followed by PAGE) was used to identify apoA-IV-containing lipoproteins in various media, and showed that butyrate stimulated the secretion of two small HDL sized particles. The influence of these secreted particles on cholesterol efflux was investigated using incubation of media with (3)H-cholesterol-labeled Fu5AH cells. The data indicate that conditioned media from Caco-2 cells treated with butyrate resulted in an increase of 20-30% in cholesterol efflux. We conclude that butyrate may regulate apoA-IV secretion and, therefore, modulate reverse cholesterol transport.

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?
Law, M. R., N. J. Wald, et al. (1994), Bmj 308(6925): 367-72.
Abstract: OBJECTIVE--To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. DESIGN--Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). MAIN OUTCOME MEASURE--Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. RESULTS--For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. CONCLUSIONS--The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

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Cholesterol Journal Articles