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  1. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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    Sillesen, H.; Amarenco, P.; Hennerici, M.G.

    2008-01-01

    BACKGROUND AND PURPOSE: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found that treatment with atorvastatin 80 mg per day reduced the risk of stroke and cardiovascular events in patients with a recent transient ischemic attack (TIA) or stroke. We hypothesized...... this benefit would be greatest in the subgroup of patients with carotid stenosis. METHODS: The SPARCL trial randomized patients with TIA or stroke within 1 to 6 months without known coronary heart disease (CHD) and low-density lipoprotein cholesterol 100 to 190 mg/dL to treatment with atorvastatin 80 mg per...

  2. Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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    Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik

    2010-01-01

    management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients....

  3. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes

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    Amarenco, Pierre; Benavente, Oscar; Goldstein, Larry B

    2009-01-01

    BACKGROUND AND PURPOSE: The SPARCL trial showed that atorvastatin 80 mg/d reduces the risk of stroke and other cardiovascular events in patients with recent stroke or transient ischemic attack (TIA). We tested the hypothesis that the benefit of treatment varies according to index event stroke...... subtype. METHODS: Subjects with stroke or TIA without known coronary heart disease were randomized to atorvastatin 80 mg/d or placebo. The SPARCL primary end point was fatal or nonfatal stroke. Secondary end points included major cardiovascular events (MCVE; stroke plus major coronary events). Cox...

  4. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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    Callahan, Alfred; Amarenco, Pierre; Goldstein, Larry B;

    2011-01-01

    To perform a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, which tested the effect of treatment with atorvastatin in reducing stroke in subjects with a recent stroke or transient ischemic attack, to explore the effects of treatment in su...

  5. Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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    Goldstein, L.B.; Amarenco, P.; Zivin, J.;

    2009-01-01

    strokes in subjects with recent stroke or transient ischemic attack (n=4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the distribution of severities of ischemic cerebrovascular outcomes. METHODS: Severity was assessed with the National Institutes of Health Stroke...... or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (P... outcome events (ischemic and hemorrhagic, Pischemic stroke (ie, excluding those having a transient ischemic attack...

  6. Baseline blood pressure, low- and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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    Amarenco, Pierre; Goldstein, Larry B; Callahan, Alfred

    2009-01-01

    AND RESULTS: The SPARCL trial randomized 4731 patients with recent stroke or transient ischemic attack (TIA) and no known coronary heart disease and LDL-C between 100 and 190 mg/dL to either atorvastatin 80 mg/d or placebo. Baseline assessment included SBP, DBP and measurements of low-density lipoprotein....... There were no interactions between any of these baseline variables and the effect of treatment on outcome strokes. CONCLUSIONS: In patients with recent stroke or TIA and no coronary heart disease, only lower baseline HDL-C predicted the risk of recurrent stroke with HDL-C, triglycerides, and LDL/HDL ratio...

  7. High blood cholesterol levels

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    ... this page: //medlineplus.gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features ... stroke, and other problems. The medical term for high blood cholesterol is lipid disorder, hyperlipidemia, or hypercholesterolemia. ...

  8. What Your Cholesterol Levels Mean

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    ... Disease Venous Thromboembolism Aortic Aneurysm More What Your Cholesterol Levels Mean Updated:Apr 3,2017 Keeping your ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  9. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study

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    Goldstein, L.B.; Amarenco, P.; Szarek, M.;

    2008-01-01

    risk was higher in those having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p age (10 y increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical interactions between these factors......: Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately......BACKGROUND: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having...

  10. Do You Know Your Cholesterol Levels?

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    ... The Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, 6.1 MB) ... Eat Smart Did you know that high blood cholesterol is a serious problem among Latinos? About one ...

  11. Americans' Cholesterol Levels Keep Falling

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    ... and 2013-2014, the CDC reported. Dr. David Friedman is chief of heart failure services at Long ... for cholesterol treatment, all seem to be working," Friedman said. The study was published online Nov. 30 ...

  12. Dairy products and plasma cholesterol levels

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    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  13. Cholesterol levels in fragile X syndrome.

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    Berry-Kravis, Elizabeth; Levin, Rebecca; Shah, Haroon; Mathur, Shaguna; Darnell, Jennifer C; Ouyang, Bichun

    2015-02-01

    Fragile X syndrome (FXS) is associated with intellectual disability and behavioral dysfunction, including anxiety, ADHD symptoms, and autistic features. Although individuals with FXS are largely considered healthy and lifespan is not thought to be reduced, very little is known about the long-term medical health of adults with FXS and no systematically collected information is available on standard laboratory measures from metabolic screens. During the course of follow up of a large cohort of patients with FXS we noted that many patients had low cholesterol and high density lipoprotein (HDL) values and thus initiated a systematic chart review of all cholesterol values present in charts from a clinic cohort of over 500 patients with FXS. Total cholesterol (TC), low density lipoprotein (LDL) and HDL were all significantly reduced in males from the FXS cohort relative to age-adjusted population normative data. This finding has relevance for health monitoring in individuals with FXS, for treatments with cholesterol-lowering agents that have been proposed to target the underlying CNS disorder in FXS based on work in animal models, and for potential biomarker development in FXS.

  14. CHOLESTEROL LEVELS AND SUICIDAL BEHAVIOR: A CASE CONTROL STUDY

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    Nikhil

    2014-06-01

    Full Text Available BACKGROUND: In modern psychiatry, there is a movement to understand mental health, not solely based on behaviors and subjective report, but also based on objective markers of illness. Several studies have focused on a relationship between serum cholesterol levels and aggressive behaviors including suicide. AIM: To identify a potential link between cholesterol and suicidal behavior. MATERIAL AND METHODS: 150 patients with psychiatry diagnosis were divided into three equal groups (50 each: those who had a recent suicidal attempt, those who had suicidal ideations but no attempts and those with psychiatry diagnosis but no suicidal ideations and attempts. Blood sample for total cholesterol level was on IPD or OPD basis. The study was started after taking approval from institute ethical committee. Analysis was done using Chi square test. OBSERVATIONS AND RESULTS: It was found that maximum patients who attempted suicide belonged to major depression and schizophrenia followed by substance dependence and bipolar affective disorder (BPAD with major depression and there was statistical difference in cholesterol levels of patients with suicide attempt, with suicidal ideations and control group. 42% and 44% of major depression and schizophrenia cases respectively had low total serum cholesterol levels (below 160 mg%. CONCLUSION: There is a potential link between serum total cholesterol levels and suicidal behavior. Taking the literature as a whole there is substantial evidence that low cholesterol levels are found in suicidal behaviors of various psychiatric illnesses especially major depressive disorder, schizophrenia, substance dependence and bipolar depressive disorder

  15. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

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    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  16. Cholesterol Levels: What You Need to Know | NIH MedlinePlus the Magazine

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    ... this page please turn Javascript on. Feature: High Cholesterol Cholesterol Levels: What You Need to Know Past Issues / Summer 2012 Table of Contents Measuring Cholesterol Levels Learn more at MedlinePlus: https://medlineplus.gov/ ...

  17. SPARCL1基因在肿瘤中的表达及作用%Expression and role of SPARCL1 gene in tumor

    Institute of Scientific and Technical Information of China (English)

    赵书杰; 周栋

    2016-01-01

    Abnormal expression of secreted protein acidic and rich in cysteine like 1 (SPARCL1 )gene is closely related to the development,metastasis and prognosis of a variety of tumors.Recent studies show that SPARCL1 gene is high expressed in glioma.The protein product of SPARCL1 gene encoded can interact with collagen,thus affecting the metastasis ability of tumor,which is positively correlated with tumor malignant de-gree.SPARCL1 gene is low expressed in gastric cancer,colorectal cancer,prostate cancer and breast cancer, which is negatively correlated with the invasion and metastasis abilities of tumors.At present,the role of speci-fic molecular mechanisms of SPARCL1 gene remains controversial. The expressions and functions of SPARCL1 gene in tumor tissues seem to depend on the tumor microenvironment.%富含半胱氨酸的酸性分泌蛋白类似蛋白1(SPARCL1)基因的异常表达与多种肿瘤的发展、转移及预后密切相关。近年来研究表明,SPARCL1基因在脑胶质瘤中表达升高,其编码的蛋白可以和胶原相互作用,从而影响肿瘤的转移能力,与肿瘤恶性程度呈正相关。SPARCL1基因在胃癌、结直肠癌、前列腺癌及乳腺癌等肿瘤组织中低表达,与肿瘤的侵袭及转移能力呈负相关。目前对于 SPARCL1基因发挥作用的具体分子机制仍存在争议,其在肿瘤组织中的表达和功能似乎依赖于肿瘤微环境。

  18. [Is there a relationship between cholesterol reduction, low levels of cholesterol and mortality?].

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    LaRosa, J C

    1995-01-01

    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  19. Association between blood cholesterol level with periodontal status of coronary heart disease patients

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    Valensia, Rosy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

    2017-02-01

    Coronary heart disease (CHD) is an abnormal narrowing of heart arteries associated with local accumulation of lipids, in the form of cholesterol and triglycerides. Periodontal disease is a chronic inflammatory that suggests link to the development of CHD. In periodontitis have been reported changes in lipid profile, include increased of cholesterol levels of blood. Objective: to analyse correlation between blood cholesterol level with periodontal status of CHD and non CHD subjects. Methods: Periodontal status and blood cholesterol level of 60 CHD and 40 non CHD subjects was measured. Result: Blood cholesterol level in CHD subjects differs from non CHD subjects (p=0.032). Blood cholesterol level correlates with pocket depth (p=0.003) and clinical attachment loss (CAL) (p=0.000) in CHD subjects. Blood cholesterol level correlates with pocket depth (p=0.010) in non CHD subjects. There is no significant correlation between blood cholesterol level and bleeding on probing (BOP) in CHD subjects. There is no significant correlation between blood cholesterol level with BOP and CAL in non CHD subjects. Conclusion: Blood cholesterol level in control group is higher than CHD patients. Blood cholesterol level positively associated with pocket depth (r=0.375) and CAL (r=0.450) in CHD patients. Blood cholesterol level is positively associated with pocket depth (r=0.404) in control group.

  20. The Effect of Biliary Sphincterotomy on Serum Cholesterol Levels in Postcholecystectomy Patients: A Pilot Study

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    Waleed M Alazmi

    2007-01-01

    Full Text Available BACKGROUND: Cholesterol, in the form of bile salts, is reabsorbed from the small intestine via the enterohepatic circulation. Biliary sphincterotomy increases the delivery of bile to the terminal ileum. If the absorptive capacity is exceeded, cholesterol excretion may increase, resulting in a decrease in serum cholesterol levels and improvement in serum lipid profiles.

  1. Trypanosoma cruzi Epimastigotes Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions

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    Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T.; Vidal, Juliana Cunha; Godinho, Joseane L. P.; De Cicco, Nuccia N. T.; Atella, Geórgia C.; de Souza, Wanderley; Cunha-e-Silva, Narcisa

    2015-01-01

    Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes. PMID:26068009

  2. Effect of serum cholesterol levels on meta-chlorophenylpiperazine-evoked neuroendocrine responses in healthy subjects.

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    Terao, T; Yoshimura, R; Ohmori, O; Takano, T; Takahashi, N; Iwata, N; Suzuki, T; Abe, K

    1997-05-01

    This study was undertaken to test the hypothesis that serum cholesterol levels might be associated with serotonergic receptor function. The participants were 10 healthy male subjects. After an overnight fast, the subjects received meta-chlorophenylpiperazine (m-CPP) or identical placebo capsules orally in a randomized, double-blind, cross-over design. Blood was obtained for measurement of prolactin, cortisol, adrenocorticotropic hormone (ACTH), and cholesterol. There were some significantly positive correlations between serum cholesterol levels and hormonal responses to m-CPP administration. These results suggest that serum cholesterol levels may be positively associated with serotonergic receptor function.

  3. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

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    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion.

  4. Correlation of Friedewald's calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital

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    Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K

    2017-01-01

    Background: One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. Aim: To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. Materials and Methods: We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P values with Friedewald's formula. Results: There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. Conclusion: This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.

  5. Knowledge of cholesterol levels and targets in patients with coronary artery disease.

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    Cheng, Susan; Lichtman, Judith H; Amatruda, Joan M; Smith, Grace L; Mattera, Jennifer A; Roumanis, Sarah A; Krumholz, Harlan M

    2005-01-01

    Little is known about the extent to which patients are aware of nationally-recommended cholesterol and lipid subfraction targets. The authors interviewed 738 patients hospitalized with coronary artery disease to assess their knowledge of their low-density lipoprotein, high-density lipoprotein, and total cholesterol levels as well as corresponding national targets. Only 8%, 8%, and 43% of patients could recall their low-density lipoprotein, high-density lipoprotein, and total cholesterol values, respectively. Only 5%, 2%, and 50% could correctly name targets for these values. Knowledge of cholesterol targets was particularly poor among women, nonwhites, and patients without any college education. Patients with multiple cardiac risk factors and patients with a previous history of cardiovascular disease were no more knowledgeable about their cholesterol targets than those without these conditions. These findings suggest that current cholesterol education efforts appear inadequate, particularly for women, nonwhites, and patients without any college education.

  6. Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus after VCO treatment

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    OKID PARAMA ASTIRIN

    2009-07-01

    Full Text Available Harini M, Astirin OP. 2009. Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus after VCO treatment. Nusantara Bioscience 1: 53-58. This study aims to determine treatment effect of VCO on blood cholesterol levels in hypercholesterolemic white rat (Rattus norvegicus L.. This study used 25 male rats of Wistar strain divided into five treatment groups, namely: control, simvastatin (1.3 mL/270 g BW, cholesterol (9:1 lard, VCO 1 (1 mL/270 g BW, and VCO 2 (1.3 mL/270 g BW. Treatment was given orally. Total cholesterol, LDL and HDL cholesterol levels were measured at day 1, day 14 and day 28. Cholesterol data (total cholesterol, LDL and HDL were analyzed by Ancova and followed by contrast test at significance level of 5%.. The results showed that treatment of VCO at different doses significantly affected the decrease in blood total cholesterol, blood LDL levels, increasing blood HDL in hipercholesterolemic white rat.

  7. Association analyses of the INSIG2 polymorphism in the obesity and cholesterol levels of Korean populations

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    Shin Hyoung

    2009-09-01

    Full Text Available Abstract Background While INSIG2 has been reported to be associated with BMI in many populations, conflicting results have prevented consensus over its role. In analyses of mice and cell cultures the gene has been found to be involved in the regulation of cholesterol synthesis; however, no relationship has been found with cholesterol metabolism in human epidemiological research. Therefore, this study attempts to assess the effect of rs7566605 near INSIG2 on both obesity- and cholesterol-related traits in Koreans. Methods The rs7566605 polymorphism was genotyped with 2,364 Koreans, and associations with obesity- and cholesterol-related traits were analyzed statistically via an ANOVA or T-test. Results Replication of an association with BMI, WHR, fat mass, fat percent, and abdominal fat area failed, and the C allele of rs7566605 was not associated significantly with total cholesterol, HDL cholesterol, or triglyceride. However, it was found in a meta-analysis of a dominant model that the C allele of rs7566605 appeared to affect the level of the total cholesterol, especially in female subjects. Conclusion We failed to show associations of rs7566605 with cholesterol- and obesity-related phenotypes, although we newly suggest the possible involvement of INSIG2 with the plasma level of the total cholesterol in women.

  8. Systematic construction of a conceptual minimal model of plasma cholesterol levels based on knockout mouse phenotypes

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Soffers, A.E.M.F.; Freidig, A.P.; Ommen, B. van; Woutersen, R.A.; Rietjens, I.M.C.M.; Graaf, A.A. de

    2010-01-01

    Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define th

  9. Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: The China Cholesterol Education Program (CCEP)

    Institute of Scientific and Technical Information of China (English)

    XIE Jiang; GUAN Fei; WANG Jia-hong; HU Da-yi

    2011-01-01

    Background The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects.Methods Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire,some of which were about basic knowledge of lipids.Results About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P <0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P<0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P <0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels.Conclusions Management of hypercholesterolemia should be an important component of health strategy in Beijing.Education is imperative for residents as well as for physicians.

  10. Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice.

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    Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S

    2015-03-01

    We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism.

  11. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study.

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    Saito, Nobue; Sairenchi, Toshimi; Irie, Fujiko; Iso, Hiroyasu; Iimura, Kyoko; Watanabe, Hiroshi; Muto, Takashi; Ota, Hitoshi

    2013-01-01

    Liver cancer a global public health concern and well known for poor prognosis. The association between low total cholesterol level and liver cancer has been reported. However, the association between low low-density lipoprotein (LDL) cholesterol levels and liver cancer is still unclear. The aim of this study was to examine the relationship between LDL cholesterol level and liver cancer mortality. A total of 16,217 persons (5,551 men and 10,666 women) aged 40-79 years in 1993 were followed until 2008. LDL cholesterol levels were divided into four categories (LDL cholesterol level for liver cancer mortality was calculated using a multivariable Cox proportional hazards model. Covariates were age, sex, alanine transaminase, body mass index, alcohol intake and smoking status, all of which were correlated with LDL cholesterol levels. There were 51 deaths (32 men and 19 women) from liver cancer. Multivariable hazard ratios of liver cancer deaths for LDL cholesterol levels of LDL cholesterol levels of 80-99 mg/dl was 1.03 (95% CI: 0.42, 2.53), and for LDL cholesterol levels of ≥120 mg/dl was 0.43 (95% CI: 0.20, 0.92) compared with LDL cholesterol levels of 100-199 mg/dl (p for trendLDL cholesterol levels are associated with elevated risk of liver cancer mortality. Low LDL cholesterol may be a predictive marker for death due to liver cancer.

  12. Impact of prescription size on statin adherence and cholesterol levels

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    Mehler Phillip S

    2007-10-01

    Full Text Available Abstract Background Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol. Methods We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression. Results After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P Conclusion In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.

  13. High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

    Institute of Scientific and Technical Information of China (English)

    Ulf Gustafsson; Staffan Sahlin; Curt Einarsson

    2003-01-01

    AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile.METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition,presence of crystals and nucleation time were analyzed.RESULTS: A subgroup of gallstone patients displayeda higher proportion of DCA in bile than gallstone free subjects.By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids)were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA.CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

  14. Isoflavone supplementation reduces low-density lipoprotein cholesterol levels in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2015-12-01

    Baseline subject characteristics and lipid profile in the two groups were comparable. In the isoflavone and control groups after 6 months of supplementation LDL cholesterol levels were 124.9 ± 35.2 mg/dL vs 112 .7 ± 29.7 mg/dL (p=0.013*, respectively, and after 12 months 116.9 ± 31.7 mg/dL vs 109.1 ± 29.8 mg/dL (p=0.086. There were no significant differences in the other lipid levels at 6 and 12 months. Conclusions Soy isoflavone supplementation for 6 months was capable of significantly reducing LDL cholesterol levels in postmenopausal women. No significant changes in total cholesterol, triacylgycerol, and HDL cholesterol were found after isoflavone supplementation.

  15. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    Science.gov (United States)

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  16. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    Science.gov (United States)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  17. Improvement of HDL- and LDL-cholesterol levels in diabetic subjects by feeding bread containing chitosan.

    Science.gov (United States)

    Ausar, S F; Morcillo, M; León, A E; Ribotta, P D; Masih, R; Vilaro Mainero, M; Amigone, J L; Rubin, G; Lescano, C; Castagna, L F; Beltramo, D M; Diaz, G; Bianco, I D

    2003-01-01

    In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy.

  18. Malaria parasite status and cholesterol level of malaria patients in parts of the IMO River Basin of Nigeria

    Institute of Scientific and Technical Information of China (English)

    Chukwuocha UM; Eke KN

    2011-01-01

    Objective:To investigate the relationship between malaria parasite status and cholesterol level of 110consenting subjects (55patients and55controls) in parts of the Imo River Basin of Nigeria. Methods:Giemsa staining was used for malaria parasite examination while Randox cholesterol kit was used for cholesterol level estimation.Results:About49 persons (90%) with malaria had low cholesterol (<180mg/dL). Highest mean cholesterol levels were274 mg/dL for study patients and220 mg/dL for controls respectively; Lowest mean cholesterol levels were168mg/dL (patients) and138 mg/dL (controls) respectively. Low cholesterol levels (<180 mg/dL) were found in patients(84%)and controls(6%) respectively. However, 16.4% of controls and 6% of patients had borderline cholesterol level (200-239mg/dL). This study establishes a significant correlation (12.9%,P<0.01) between malaria parasite status and cholesterol level.Conclusions:These findings imply that cholesterol level estimation may be a potential concurrent and valuable diagnosis for malaria status.

  19. POSSIBILITIES FOR THE REDUCTION OF FAT AND CHOLESTEROL LEVEL IN MEAT ANIMALS

    Directory of Open Access Journals (Sweden)

    Slavko Čepin

    2000-06-01

    Full Text Available The majority of consumers refuse meat with higher levels of fat, because of possible association between high levels of saturated fat, cholesterol and heart disease. The meat production tries to fit consumers preferences with lowering fat content of meat. Such meat should also contain less cholesterol. In the following contribution the possibilities for reducing fat and cholesterol content and altering fatty acid composition of meat are discussed. In meat animals the estimated heritability for fat content is relatively high (between 0.3 and 0.6. This means that selection represents a powerful tool for fat reduction. Even better possibility for reducing fat and altering fatty acid composition is adequate nutrition. The decrease of animal age and weight at slaughter can also reduce carcass fat content. Also the use of transgenic animals and different growth stimulators represents a wide range of possibilities to reduce fat content in farm animals.

  20. Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory.

    Science.gov (United States)

    Leritz, Elizabeth C; McGlinchey, Regina E; Salat, David H; Milberg, William P

    2016-04-01

    We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging.

  1. Changes during hibernation in different phospholipid and free and esterified cholesterol serum levels in black bears

    Science.gov (United States)

    Chauhan, V.; Sheikh, A.; Chauhan, A.; Tsiouris, J.; Malik, M.; Vaughan, M.

    2002-01-01

    During hibernation, fat is known to be the preferred source of energy. A detailed analysis of different phospholipids, as well as free and esterified cholesterol, was conducted to investigate lipid abnormalities during hibernation. The levels of total phospholipids and total cholesterol in the serum of black bears were found to increase significantly in hibernation as compared with the active state. Both free and esterified cholesterol were increased in the hibernating state in comparison with the active state (P catabolism of phospholipids and cholesterol is decreased during hibernation in black bears, leading to their increased levels in the hibernating state as compared with the active state. In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears. It is proposed that the increase of these lipids may be due to the altered metabolism of lipoproteins that are responsible for the clearance of the lipids. ?? 2002 E??ditions scientifiques et me??dicales Elsevier SAS and Socie??te?? franc??aise de biochimie et biologie mole??culaire. All rights reserved.

  2. Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors.

    Directory of Open Access Journals (Sweden)

    Elahe A Mostaghel

    Full Text Available Prostate cancer (PCa is the second most common cancer in men. Androgen deprivation therapy (ADT leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC. Theories underlying the development of CRPC include androgen receptor (AR mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049 and intratumoral levels of testosterone (R = 0.41, p = 0.0023 in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025 Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the

  3. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

  4. Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters.

    Science.gov (United States)

    Wilson, T A; DeSimone, A P; Romano, C A; Nicolosi, R J

    2000-09-01

    The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol

  5. Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels

    Directory of Open Access Journals (Sweden)

    Hinds David A

    2004-11-01

    Full Text Available Abstract Association studies are used to identify genetic determinants of complex human traits of medical interest. With the large number of validated single nucleotide polymorphisms (SNPs currently available, two limiting factors in association studies are genotyping capability and costs. Pooled DNA genotyping has been proposed as an efficient means of screening SNPs for allele frequency differences in case-control studies and for prioritising them for subsequent individual genotyping analysis. Here, we apply quantitative pooled genotyping followed by individual genotyping and replication to identify associations with human serum high-density lipoprotein (HDL cholesterol levels. The DNA from individuals with low and high HDL cholesterol levels was pooled separately, each pool was amplified by polymerase chain reaction in triplicate and each amplified product was separately hybridised to a high-density oligonucleotide array. Allele frequency differences between case and control groups with low and high HDL cholesterol levels were estimated for 7,283 SNPs distributed across 71 candidate gene regions spanning a total of 17.1 megabases. A novel method was developed to take advantage of independently derived haplotype map information to improve the pooled estimates of allele frequency differences. A subset of SNPs with the largest estimated allele frequency differences between low and high HDL cholesterol groups was chosen for individual genotyping in the study population, as well as in a separate replication population. Four SNPs in a single haplotype block within the cholesteryl ester transfer protein (CETP gene interval were significantly associated with HDL cholesterol levels in both populations. Our study is among the first to demonstrate the application of pooled genotyping followed by confirmation with individual genotyping to identify genetic determinants of a complex trait.

  6. Evidence for low high-density lipoprotein cholesterol levels in Australian indigenous peoples: a systematic review

    OpenAIRE

    Lyons, Jasmine G.; O’Dea, Kerin; Karen Z Walker

    2014-01-01

    Background Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia’s Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors...

  7. Serum Cholesterol Level Nomograms for Iranian Population; Suggestion for National Cut-Offs

    Directory of Open Access Journals (Sweden)

    Mostafa Hosseini

    2013-02-01

    Full Text Available Background: High cholesterol levels are associated with increased risk of coronary heart disease and stroke. Understanding the distribution of serum cholesterol levels in each country is valuable index for use in public health planning. This study aimed to construct nomograms of total cholesterol (TC levels and establish the cut-points specific to Iranian population.Methods: Data on serum TC levels of 19,630 non-institutionalized individuals aged 25-64 years from third national survey on non-communicable diseases (SuRFNCD in 2007 were used to construct cholesterol nomograms. We proposed cutoff values for borderline and high TC levels based on rounded 75th and 90th percentiles in three age groups (25-34, 35-44 and 45-64 respectively.Results: Average yearly increase of TC for males up to the age of 45 and females up to 64 were 1.15 and 1.03 mg/dl, respectively. TC levels were higher in females. In males, cutoff values for "borderline and high" TC levels were 195 and 220 mg/dl in 25-34, 210 and 240 mg/d in 35-44 and 215 and 245 mg/dl in 45-64 years old individuals. In women, these values were 200 and 225 mg/dl in 25-34,215 and 240 mg/dl in 35-44 and 235 and 265 mg/dl in 45-64 years old individuals respectively.Conclusion: Since TC levels are different in two sexes and change with age, we proposed different cutoffs for sex and age group. We think these cutoffs could be used in national public health planning.

  8. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

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    Eussen Simone RBM

    2011-10-01

    Full Text Available Abstract Background To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. Methods and Results The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. Conclusion We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (reabsorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory mechanisms.

  9. Cholesterol-Induced Suppression of Membrane Elastic Fluctuations at the Atomistic Level

    Science.gov (United States)

    Molugu, Trivikram R.

    2017-01-01

    Applications of solid-state NMR spectroscopy for investigating the influences of lipid-cholesterol interactions on membrane fluctuations are reviewed in this paper. Emphasis is placed on understanding the energy landscapes and fluctuations at an emergent atomistic level. Solid-state 2H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C–2H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of 13C–1H bonds are obtained in separated local-field NMR spectroscopy. The distributions of RQC or RDC values give nearly complete profiles of the order parameters as a function of acyl segment position. Measured equilibrium properties of glycerophospholipids and sphingolipids including their binary and tertiary mixtures with cholesterol show unequal mixing associated with liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids and may drive the formation of lipid rafts. In addition relaxation time measurements enable one to study the molecular dynamics over a wide time-scale range. For 2H NMR the experimental spin-lattice (R1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (SCD) due to collective slow dynamics over mesoscopic length scales. The functional dependence for the liquid-crystalline lipid membranes is indicative of viscoelastic properties as they emerge from atomistic-level interactions. A striking decrease in square-law slope upon addition of cholesterol denotes stiffening relative to the pure lipid bilayers that is diminished in the case of lanosterol. Measured equilibrium properties and relaxation rates infer opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale that potentially affects lipid raft formation in cellular membranes. PMID:27154600

  10. Cholesterol-induced suppression of membrane elastic fluctuations at the atomistic level.

    Science.gov (United States)

    Molugu, Trivikram R; Brown, Michael F

    2016-09-01

    Applications of solid-state NMR spectroscopy for investigating the influences of lipid-cholesterol interactions on membrane fluctuations are reviewed in this paper. Emphasis is placed on understanding the energy landscapes and fluctuations at an emergent atomistic level. Solid-state (2)H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C-(2)H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of (13)C-(1)H bonds are obtained in separated local-field NMR spectroscopy. The distributions of RQC or RDC values give nearly complete profiles of the order parameters as a function of acyl segment position. Measured equilibrium properties of glycerophospholipids and sphingolipids including their binary and tertiary mixtures with cholesterol show unequal mixing associated with liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids and may drive the formation of lipid rafts. In addition relaxation time measurements enable one to study the molecular dynamics over a wide time-scale range. For (2)H NMR the experimental spin-lattice (R1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (SCD) due to collective slow dynamics over mesoscopic length scales. The functional dependence for the liquid-crystalline lipid membranes is indicative of viscoelastic properties as they emerge from atomistic-level interactions. A striking decrease in square-law slope upon addition of cholesterol denotes stiffening relative to the pure lipid bilayers that is diminished in the case of lanosterol. Measured equilibrium properties and relaxation rates infer opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale that potentially affects lipid raft formation in cellular membranes.

  11. Effect of saturated and unsaturated fat on the performance, serum and meat cholesterol level in broilers

    Directory of Open Access Journals (Sweden)

    M. Senthilkumar

    2013-06-01

    Full Text Available Aim: A biological trial was conducted for a period of seven weeks to study the effect of graded levels of tallow (saturated and sunflower oil (un saturated or combination of both on the production performance, carcass characteristics, serum and meat cholesterol level in broilers. Materials and Methods: The experimental feeds were prepared by the addition of tallow (2% and 4% and sunflower oil (2% and 4% either alone or in combination of both (SF oil 1% + tallow 1% and SF oil 2% + tallow 2%. Results: Neither the fat source (sunflower oil or tallow nor their combinations had influenced the growth rate, feed consumption, feed efficiency, livability and carcass characteristics in broilers. However, at 49 days of age, broilers fed with tallow alone had higher (P<0.01 abdominal fat than the rest of the treatment groups. When compared to control and tallow alone fed groups, the broilers fed with sunflower oil alone and mixture of sunflower oil and tallow had significantly (P<0.01 lower total serum and meat cholesterol level. Conclusion: The data suggest that the abdominal fat yield, serum and meat total cholesterol level of commercial broilers are inversely proportional to the level of polyunsaturated fatty acids in the diet. [Vet World 2013; 6(3.000: 159-162

  12. Systematic construction of a conceptual minimal model of plasma cholesterol levels based on knockout mouse phenotypes knockout mouse phenotypes

    NARCIS (Netherlands)

    Pas, van de N.; Soffers, A.E.M.F.; Freidig, A.P.; Ommen, van B.; Woutersen, R.A.; Rietjens, I.M.C.M.; Graaf, de A.A.

    2010-01-01

    Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define th

  13. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

    Science.gov (United States)

    Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

  14. Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin : cholesterol acyltransferase and lipid transfer protein activity levels

    NARCIS (Netherlands)

    Riemens, SC; vanTol, A; Hoogenberg, K; vanGent, T; Scheek, LM; Sluiter, WJ; Dullaart, RPF

    1997-01-01

    Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) choles

  15. Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type-2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lund, S.S.; Petersen, Martin; Frandsen, M.

    2008-01-01

    Objective. Low density lipoprotein cholesterol (LDL-C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL-C profile in patients with type-2 diabetes (T2DM......). We aimed to study the postprandial levels of LDL-C in T2DM patients. Material and methods. After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat-rich meal of 3,515 kJ containing 54 % fat, 13 % protein and 33 % carbohydrates. Only drinking water...... inhibitors; lipoproteins; low density lipoprotein cholesterol (LDL-C); postprandial period; statins; ultracentrifugation...

  16. Low cell cholesterol levels increase NFkappaB activity through a p38 MAPK-dependent mechanism.

    Science.gov (United States)

    Calleros, Laura; Lasa, Marina; Toro, María J; Chiloeches, Antonio

    2006-12-01

    Cholesterol, p38 MAPK and NFkappaB have been shown to participate in inflammation and cellular differentiation. Here, we examined the effect of cholesterol on NFkappaB-dependent transcription and the mechanisms underlying this effect in NIH3T3 cells. We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment resulted in a significant increase in NFkappaB-dependent transcription, NFkappaB-DNA binding, IkappaBalpha degradation and p65/NFkappaB translocation to the nucleus, and the addition of exogenous cholesterol reversed these effects. Previously, we have shown that low cell cholesterol levels activate p38 MAPK. Here, we found that inhibition of p38 MAPK with the specific inhibitor SB203580 blocked the increase in NFkappaB activity, IkappaBalpha degradation and p65/NFkappaB translocation to the nucleus induced by cholesterol depletion. Moreover, the inhibition of the p38 MAPK downstream effector MSK1 with the specific inhibitor H89, or the overexpression of a kinase defective MSK1 abrogated the NFkappaB-dependent transcription induced by cholesterol depletion. On the other hand, the transactivation potential of p65/NFkappaB depends on phosphorylation of S276 by MSK1. We observed that cholesterol depletion increased the p65/NFkappaB transactivation capacity. This effect was reversed by cell cholesterol repletion or incubation with the SB203580 inhibitor. Moreover, the expression of a p65/NFkappaB S276A mutant was insensitive to cholesterol depletion. Together, our results demonstrate that cholesterol depletion induces NFkappaB transcriptional activity, not only by affecting the IkappaBalpha degradation and the translocation of p65/NFkappaB to the nucleus, but also regulating the p65/NFkappaB transactivating potential through a p38 MAPK/MSK1 mediated pathway.

  17. Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Shu Meguro

    2014-01-01

    Full Text Available Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n=133, 115 men and 18 women; age 64.7±11.5 years; HbA1c 8.1±1.6%. Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2±22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r=−0.450, P<0.01, triglyceride (r=0.445, P<0.01, and high sensitive C-reactive protein (r=0.316, P<0.01 but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β=−0.411, P<0.01 and high sensitive C-reactive protein (β=0.193, P<0.05. Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

  18. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-05-28

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.

  19. Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level

    Science.gov (United States)

    Paavola, Timo; Kuusisto, Sanna; Jauhiainen, Matti; Kakko, Sakari; Kangas-Kontio, Tiia; Metso, Jari; Soininen, Pasi; Ala-Korpela, Mika; Bloigu, Risto; Hannuksela, Minna L.; Savolainen, Markku J.

    2017-01-01

    Objective The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. Methods HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. Results While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (pHDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, pHDL2 was reduced in men with early CHD (pHDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, pHDL2 to total HDL was associated with MetS (pHDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed. PMID:28207870

  20. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  1. Fluoxetine Decreased Serum Total Cholesterol and Triglyceride Levels in a Hypercholesterolemic Patient with Postpartum Depression

    Directory of Open Access Journals (Sweden)

    Hossein Khalili

    2006-05-01

    Full Text Available Objective: To report the case of a 28-year old hypercholesterolemic female with postpartum depression, whose triglyceride (TG and total cholesterol (TC levels decreased while being treated with fluoxetine. Method: A 28-year old female, with a diagnosis of major depressive disorder with postpartum onset based on DSM-IV criteria, was hospitalized at a mental health hospital. Her past history included another episode of depression 4 months after giving birth to her second child, which was 12 years prior to her recent episode. Her serum total cholestrol and triglyceride levels were measured prior to the initiation of medication. Then fluoxetine was initiated at a daily dose of 20 mg and had been increased to 40 mg per day at the time of discharge. The lipid profile measurements was repeated at week 4 and 8 following treatment. Results: Total cholesterol level was reduced from 242 mg/dL at baseline to 224 mg/dL at week 4 and to 202 mg/dL at week 8; triglyceride level was decreased from 516 mg/dL to 448 mg/dL at week 4 and to 404 mg/dL at week 8. Conclusions: Fluoxetine may be an appropriate treatment for hyperlipidemic women with postpartum depression..

  2. IL-1 regulates the Cyp7a1 gene and serum total cholesterol level at steady state in mice.

    Science.gov (United States)

    Kojima, Misaki; Ashino, Takashi; Yoshida, Takemi; Iwakura, Yoichiro; Sekimoto, Masashi; Degawa, Masakuni

    2009-02-06

    We examined the role of hepatic interleukin (IL)-1alpha/beta in serum total cholesterol homeostasis using male and female IL-1-knockout (KO) mice and wild-type (WT) mice. Serum total cholesterol level was higher in males than in females in WT and KO mice. The difference between sexes was closely correlated with the difference in gene expression level of cholesterol 7alpha-hydroxylase (Cyp7a1), a rate-limiting enzyme for bile acid synthesis. No significant sex difference in gene expression level of 3-hydroxy-3-methylglutaryl-CoA reductase, a rate-limiting enzyme for cholesterol synthesis, was observed in WT mice. Interestingly, the gene expression level of hepatic Cyp7a1 was lower in KO mice than in sex-matched WT mice, while the serum total cholesterol level was the opposite. The present findings demonstrate that IL-1alpha and IL-1beta are positive regulators for the Cyp7a1 gene in steady-state mice and that Cyp7a1 is one of the factors that mediate the difference in serum total cholesterol level between sexes.

  3. Serum specific vasopressin-degrading activity is related to blood total cholesterol levels in men but not in women.

    Science.gov (United States)

    Ramírez-Expósito, María Jesús; Arrazola, Marcelina; Carrera-González, María Pilar; Arias de Saavedra, José Manuel; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, José Manuel

    2012-07-01

    The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.

  4. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG;

    2008-01-01

    CONTEXT: We have previously shown that rare mutations in the apolipoprotein B gene (APOB) may result in not only severe hypercholesterolemia and ischemic heart disease but also hypocholesterolemia. Despite this, common single-nucleotide polymorphisms (SNPs) in APOB have not convincingly been...... on cholesterol and apolipoprotein B levels. However, as predicted from the magnitude of the observed LDL cholesterol effects, none of these SNPs predicted risk of ischemic heart disease prospectively in the general population, in a case-control study, or as haplotypes. CONCLUSIONS: Multiple common and rare...... demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN...

  5. CDD/SPARCLE: functional classification of proteins via subfamily domain architectures

    Science.gov (United States)

    Marchler-Bauer, Aron; Bo, Yu; Han, Lianyi; He, Jane; Lanczycki, Christopher J.; Lu, Shennan; Chitsaz, Farideh; Derbyshire, Myra K.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Lu, Fu; Marchler, Gabriele H.; Song, James S.; Thanki, Narmada; Wang, Zhouxi; Yamashita, Roxanne A.; Zhang, Dachuan; Zheng, Chanjuan; Geer, Lewis Y.; Bryant, Stephen H.

    2017-01-01

    NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. PMID:27899674

  6. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (JUPITER).

    Science.gov (United States)

    Everett, Brendan M; Mora, Samia; Glynn, Robert J; MacFadyen, Jean; Ridker, Paul M

    2014-12-01

    Recent US guidelines expand the indications for high-intensity statin therapy, yet data on the safety of attaining very low-density lipoprotein cholesterol (LDL-C) levels are scarce. Among 16,304 participants in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) with on-treatment LDL-C levels, we identified 767 who did and 7,387 who did not achieve LDL-C JUPITER, achieving LDL-C levels <30 mg/dl with high-intensity statin therapy appeared to be generally well tolerated but associated with certain adverse events, including more physician-reported diabetes, hematuria, hepatobiliary disorders, and insomnia. These data may guide the monitoring of patients on intensive statin therapy and adverse events in trials of therapies that lead to very low LDL-C levels.

  7. Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

    Science.gov (United States)

    Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri

    2015-01-01

    People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

  8. Detecting Elevated Cholesterol Levels: Part 1: How accurate is the Reflotron?

    Science.gov (United States)

    Reimer, H L; Elford, R W; Shumak, S

    1991-11-01

    To assess accuracy of blood cholesterol measurements in the office, fingerprick blood cholesterol assays by a dry reagent chemistry analyzer were compared in 151 patients with simultaneous venipuncture cholesterol assays by standard laboratory methods. Compared with the laboratory assay, seven of eight analyzers had total absolute biases less than 5%. Variability in results was comparable to that of community laboratories.

  9. Detecting Elevated Cholesterol Levels: Part 1: How accurate is the Reflotron?

    OpenAIRE

    Reimer, H.L.; Elford, R.W.; Shumak, S.

    1991-01-01

    To assess accuracy of blood cholesterol measurements in the office, fingerprick blood cholesterol assays by a dry reagent chemistry analyzer were compared in 151 patients with simultaneous venipuncture cholesterol assays by standard laboratory methods. Compared with the laboratory assay, seven of eight analyzers had total absolute biases less than 5%. Variability in results was comparable to that of community laboratories.

  10. Relationships between birth weight and serum cholesterol levels in healthy Japanese late adolescents.

    Science.gov (United States)

    Ito, Sanae; Uenishi, Kazuhiro; Ishida, Hiromi; Uemura, Yukari; Kodama, Momoko; Fukuoka, Hideoki

    2014-01-01

    Poor growth in utero has been suggested to be associated with adverse levels of serum cholesterol concentrations in later life. In Asia, there have only been a limited number of studies examining the relationship between fetal status and serum lipids, especially in adolescents. The objective of this study was to examine the relationships between birth weight and serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels; adjusting for current physical status including percent body fat, physical activity and nutrient intake in healthy Japanese late adolescents. The data of 573 late adolescents with an average age of 17.6 (287 boys and 286 girls) who underwent physical examinations which included blood sampling and who had all the required data, were analyzed. Birth weight was obtained from their maternal and child health handbook. Multiple regression analysis showed that birth weight was positively associated with serum HDL in girls, independently of percent body fat or fat intake, when adjusted for current body height and weight. There were no associations between birth weight and serum HDL in boys, or serum LDL in either sex.

  11. Quantitative comparison of the efficacy of various compounds in lowering intracellular cholesterol levels in Niemann-Pick type C fibroblasts.

    Directory of Open Access Journals (Sweden)

    Zachary T Wehrmann

    Full Text Available Niemann-Pick Type C disease (NPC is a lethal, autosomal recessive disorder caused by mutations in the NPC1 and NPC2 cholesterol transport proteins. NPC's hallmark symptoms include an accumulation of unesterified cholesterol and other lipids in the late endosomal and lysosomal cellular compartments, causing progressive neurodegeneration and death. Although the age of onset may vary in those affected, NPC most often manifests in juveniles, and is usually fatal before adolescence. In this study, we investigated the effects of various drugs, many of which modify the epigenetic control of NPC1/NPC2 gene expression, in lowering the otherwise harmful elevated intracellular cholesterol levels in NPC cells. Our studies utilized a previously described image analysis technique, which allowed us to make quantitative comparisons of the efficacy of these drugs in lowering cholesterol levels in a common NPC1 mutant model. Of the drugs analyzed, several that have been previously studied (vorinostat, panobinostat, and β-cyclodextrin significantly lowered the relative amount of unesterified cellular cholesterol, consistent with earlier observations. In addition, a novel potential treatment, rapamycin, likewise alleviated the NPC phenotype. We also studied combinations of effective compounds with β-cyclodextrin; the addition of β-cyclodextrin significantly enhanced the cholesterol-lowering activity of vorinostat and panobinostat, but had mixed effects with rapamycin. Collectively, these results may provide a basis for the eventual development of improved NPC therapies.

  12. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice.

    Directory of Open Access Journals (Sweden)

    Rosanna W S Chung

    Full Text Available Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [(14C]cholesterol and [(3H]sitostanol in male C57BL/6 mice fed a high-fat (HF diet with or without 0.6% wt/wt SM for 18 days; and (ii hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt for 4 weeks. Mice supplemented with SM (0.6% wt/wt had significantly increased fecal lipid and cholesterol output and reduced hepatic [(14C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (-30%. Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (-18%. Total liver lipid (mg/organ was significantly reduced in the SM-supplemented mice (-33% and -40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively, as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet.

  13. Effects of lifestyle interventions on high-density lipoprotein cholesterol levels.

    Science.gov (United States)

    Roussell, Michael A; Kris-Etherton, Penny

    2007-03-01

    This review summarizes intervention studies that evaluated the effects of lifestyle behaviors on high-density lipoprotein-cholesterol (HDL-C) levels. Current diet and lifestyle recommendations beneficially affect HDL-C. Individual lifestyle interventions that increase HDL-C include: a healthful diet that is low (7-10% of calories) in saturated fat and sufficient in unsaturated fat (15-20% of calories), regular physical activity, attaining a healthy weight, with moderate alcohol consumption, and cessation of cigarette smoking. Combining a healthy diet with weight loss and physical activity can increase HDL-C 10% to 13%. When combined with interventions that beneficially affect other cardiovascular disease risk factors, this increase in HDL-C is expected to contribute to a overall reduction in cardiovascular disease risk.

  14. Correlation between High Density Lipoprotein Cholesterol (HDL) Level and Aerobic Activity Level.

    Science.gov (United States)

    1987-04-01

    over a 40 day period for HDtJICholesteroll and Total Choleis- added with the "reverse" technique, This technique is only poai- tarot . The results are...Stand- tarot and Total Cholestero levels, it is beat that eet laoatr ard and a control Serum were each analyzed 10 times giving the * determinle its

  15. Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels

    DEFF Research Database (Denmark)

    Haase, C L; Frikke-Schmidt, R; Nordestgaard, B G

    2011-01-01

    OBJECTIVES: To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population. BACKGROUND: Epidemiologically, risk of IHD is inversely related to HDL cholesterol le...... effects of mutations in adenovirus-transfected mice. RESULTS: We identified a new mutation, A164S (1 : 500 in the general population), which predicted hazard ratios for IHD, MI and total mortality of 3.2 [95% confidence interval (CI): 1.6-6.5], 5.5 (95% CI: 2.6-11.7) and 2.5 (95% CI: 1......164S heterozygotes had normal plasma lipid and lipoprotein levels, including HDL cholesterol and apoA-I, and this finding was confirmed in adenovirus-transfected mice. CONCLUSIONS: A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality...

  16. Comparison of serum leptin, glucose, total cholesterol and total protein levels in fertile and repeat breeder cows

    Directory of Open Access Journals (Sweden)

    Saime Guzel

    2014-12-01

    Full Text Available In the present study we measured serum glucose, leptin, total cholesterol and total protein concentrations in repeat breeder cows and compared them with fertile cows. For this aim, 20 repeat breeder cows and 20 fertile cows were used as material. Repeat breeder cows were found to have lower levels of leptin and glucose as compared with fertile ones. No significant differences in total cholesterol and total protein levels were observed between the two groups. No significant correlation of leptin with glucose, total cholesterol and total protein was observed in fertile and repeat breeder cows. Low concentrations of glucose and leptin can have some effects on reproductive problems as repeat breeder and help to understand potential mechanisms impairing fertility in repeat breeder cows.

  17. Relationship between serum cholesterol levels and meta-chlorophenylpiperazine-induced cortisol responses in healthy men and women.

    Science.gov (United States)

    Terao, T; Nakamura, J; Yoshimura, R; Ohmori, O; Takahashi, N; Kojima, H; Soeda, S; Shinkai, T; Nakano, H; Okuno, T

    2000-10-30

    We investigated the effect of cholesterol on serotonergic receptor function in 20 healthy male and 10 healthy female subjects using cortisol responses to meta-chlorophenylpiperazine (m-CPP) neuroendocrine challenge tests. M-CPP, a metabolite of the antidepressant trazodone, has been widely used in psychopharmacology research as a probe of serotonin function. In the human brain, m-CPP binds both to various serotonergic receptors, mainly 5-HT(2C), and to alpha(2)-adrenoceptors. After an overnight fast, the subjects received m-CPP (0.5 mg/kg) or identical placebo capsules orally in a randomized, double blind, crossover design. Blood was obtained for measurement of cholesterol and cortisol. In some analyses, especially in males, there were significant positive correlations between serum cholesterol levels and cortisol responses. These findings suggest the possibility that serum cholesterol levels may be positively associated with serotonergic receptor function. The existence of such an association may provide an explanation for reported increases in depression, suicide and violence in individuals with low or lowered cholesterol.

  18. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Desmarchelier Charles

    2012-03-01

    Full Text Available Abstract Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.

  19. Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    East, C.; Grundy, S.M.; Bilheimer, D.W.

    1986-11-28

    Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia.

  20. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  1. SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Jing Yu; Jie-Kai Yu; Wei-Ting Ge; Han-Guang Hu; Ying Yuan; Shu Zheng

    2011-01-01

    AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients.METHODS: One hundred and fifty-six CRC patients were followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was per-formed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers.RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. Ac-cording to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 ex-pression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

  2. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

    Directory of Open Access Journals (Sweden)

    Md. Ibrahim Khalil

    2015-01-01

    Full Text Available The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO- induced myocardial infarction (MI in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI, triglycerides (TG, total cholesterol (TC, lipid peroxidation (LPO products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40 were pretreated orally with Tualang honey (3 g/kg/day for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB, lactate dehydrogenase (LDH, and aspartate transaminase (AST, cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO products (TBARS and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST. Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

  3. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice

    Science.gov (United States)

    Miller, Jordan D.; Weiss, Robert M.; Serrano, Kristine M.; Brooks, Robert M.; Berry, Christopher J.; Zimmerman, Kathy; Young, Stephen G.; Heistad, Donald D.

    2009-01-01

    Background Treatment of hyperlipidemia produces functional and structural improvements in atherosclerotic vessels. However, the effects of treating hyperlipidemia on the structure and function of the aortic valve has been controversial, and any effects could be confounded by pleiotropic effects of hypolipidemic treatment. The goal of this study was to determine whether reducing elevated plasma lipid levels with a “genetic switch” in Reversa mice (Ldlr−/−/Apob100/100/Mttpfl/fl/Mx1Cre+/+) reduces oxidative stress, reduces proosteogenic signaling, and retards the progression of aortic valve disease. Methods and Results After 6 months of hypercholesterolemia, Reversa mice exhibited increases in superoxide, lipid deposition, myofibroblast activation, calcium deposition, and pro-osteogenic protein expression in the aortic valve. Maximum aortic valve cusp separation, as judged by echocardiography, was not altered. During an additional 6 months of hypercholesterolemia, superoxide levels, valvular lipid deposition, and myofibroblast activation remained elevated. Furthermore, calcium deposition and pro-osteogenic gene expression became more pronounced and the aortic cusp separation decreased from 0.85 ± 0.04 to 0.70 ± 0.04 mm (mean ± SE; p < 0.05). Rapid normalization of cholesterol levels at 6 months of age (by inducing expression of Cre recombinase) normalized aortic valve superoxide levels, decreased myofibroblast activation, reduced valvular calcium burden, suppressed pro-osteogenic signaling cascades, and prevented the reductions in aortic valve cusp separation. Conclusions Collectively, these data indicate that reducing plasma lipid levels by genetic inactivation of the mttp gene in hypercholesterolemic mice with early aortic valve disease normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of aortic valve stenosis. PMID:19433756

  4. Association between periodontal disease and plasma levels of cholesterol and triglycerides

    Directory of Open Access Journals (Sweden)

    Adriana Jaramillo

    2013-05-01

    Full Text Available Objective: Untreated periodontal disease seems to cause low grade systemic inflammation and blood lipid alteration leading to increased cardiovascular disease risk. To start testing this hypothesis in Colombian patients, a multicentre study was conducted including the three main state capitals: Bogotá, Medellín and Cali. Methods: In this study 192 (28.4% advanced and 256 (37.8% moderate periodontitis patients were  investigated for socio-demographic variables, city of precedence, periodontal parameters, smoking, red complex periodontopathic bacteria, serum antibodies against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and blood lipids including total cholesterol, HDL, LDL and triglycerides (TG. Those parameters were compared to 229 (33.8% controls having periodontal health or gingivitis. Results: Advanced periodontitis had worst periodontal indexes, than moderate periodontitis and controls. Interestingly, higher HDL and TG levels were present in periodontitis. BMI <30 and smoking were associated with increased HDL, HDL-35, LDL and TG, while glycemia >100 mg/dL associated with HDL, HDL-35 and TG. Tannerella forsythia showed a significant association with HDL-35 in bivariate analysis and serum IgG1 against P. gingivalis associated with HDL-35 and serum IgG1 against T. forsythia associated with TG and serum IgG2 against A. actinomycetemcomitans correlated with levels of HDL y HDL-35. In logistic regression the periodontitis patients from Cali presented reduced HDL levels as compared to Bogotá and Medellín patients. Presence of IgG1 antibodies against P. gingivalis and A. actinomycetemcomitans correlated with reduced HDL levels. Conclusion: This study confirmed that untreated periodontitis generates alteration in serum lipid levels and systemic bacterial exposure against important periodontopathic bacteria seems to be the biological link. 

  5. Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum

    Directory of Open Access Journals (Sweden)

    Olarewaju M. Oluba

    2012-01-01

    Full Text Available In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ. Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC and low-density cholesterol (LDL-C contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C. The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

  6. Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Morón Francisco J

    2007-01-01

    Full Text Available Abstract Background Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10 has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI and polycystic ovary syndrome (PCOS, a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5 encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A with several cardiovascular risk factors related to metabolic syndrome in general population. Methods Anthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille, recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR. Results Genotype association analysis was significant for BMI (p ≤ 0.041, diastolic blood pressure (p = 0.015 and HDL-cholesterol levels (p = 0.025. Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP (0.0005 ≤ p ≤ 0.006 and total cholesterol levels (0.001 ≤ p ≤ 0.029. In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029. Conclusion As its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our

  7. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab.

    Science.gov (United States)

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    Patients with familial hypercholesterolemia or statin intolerance are especially challenging to manage since LDL cholesterol levels often remain considerably elevated despite clinicians' best efforts. With statins regarded as first-line pharmacologic therapy by the current American College of Cardiology/American Heart Association guidelines to reduce LDL cholesterol and cardiovascular risk, there is now a critical need to determine when other agents will play a role beyond maximally tolerated statin therapy and lifestyle changes. In this review, we take a closer look at evolocumab (Repatha(®)), one of the new injectable human monoclonal antibodies to PCSK9 and its efficacy and safety properties from the results of various trials.

  8. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects.

    Science.gov (United States)

    Pungcharoenkul, Kanit; Thongnopnua, Phensri

    2011-11-01

    The impact of consuming curcuminoids containing curcumin at 500 mg/day and 6 g/day for 7 days on plasma antioxidant capacity and serum cholesterol level were determined by using vitamin E 200 IU/day consumption as a comparison. Group A and group B subjects consumed 500 mg and 6 g curcumin, respectively, but group C subjects consumed vitamin E 200 IU. By using the oxygen radical absorbance capacity (ORAC) assay, it was found that plasma antioxidant capacity of group A rose from a baseline of 13% to 24% on day 1 and day 7, as against a 19-20% increase for group B. Serum cholesterol and triglyceride levels were significantly decreased after curcumin treatment at 500 mg/day. By consuming vitamin E, both ORAC values and plasma α-tocopherol concentrations were significantly increased, but only very slight responses on serum cholesterol or triglyceride levels were observed. It is therefore suggested that curcumin supplement would not be appropriate for healthy people except for reducing serum cholesterol or triglyceride levels. The dosage of a daily curcumin supplement at 500 mg is more effective than 6 g, although vitamin E is also considered to be an effective antioxidant supplement.

  9. Effects of simvastatin on bone regeneration in the mandibles of ovariectomized rats and on blood cholesterol levels.

    Science.gov (United States)

    Junqueira, Juliana C; Mancini, Maria N G; Carvalho, Yasmin R; Anbinder, Ana Lia; Balducci, Ivan; Rocha, Rosilene F

    2002-12-01

    The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.

  10. The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

    NARCIS (Netherlands)

    Snel, M.; Sleddering, M.A.; Pijl, H.; Nieuwenhuizen, W.F.; Frölich, M.; Havekes, L.M.; Romijn, J.A.; Jazet, I.M.

    2010-01-01

    Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary suppleme

  11. Enhanced serum cholesterol and triglyceride levels in bulimia nervosa: relationships to psychiatric comorbidity, psychopathology and hormonal variables.

    Science.gov (United States)

    Monteleone, Palmiero; Santonastaso, Paolo; Pannuto, Marilena; Favaro, Angela; Caregaro, Lorenza; Castaldo, Eloisa; Zanetti, Tatiana; Maj, Mario

    2005-04-30

    Increased levels of cholesterol have been reported in patients with bulimia nervosa (BN), but all but one of the published studies were performed on non-fasting subjects, which limits the interpretation of this finding. Moreover, the relationships between serum lipids and comorbid psychiatric disorders or bulimic psychopathology have scarcely been investigated. We measured serum levels of total cholesterol, triglycerides, glucose, 17beta-estradiol and thyroid hormones in 75 bulimic women and 64 age-matched healthy females after an overnight fast. Compared with healthy women, bulimic patients exhibited significantly enhanced serum levels of cholesterol and triglycerides, but similar values of glucose, 17beta-estradiol, FT3 and FT4. No significant differences emerged in these variables between patients with or without comorbid depression, borderline personality disorder or lifetime anorexia nervosa. Circulating cholesterol was positively correlated to the patients' drive for thinness, ineffectiveness, enteroceptive awareness and impulse regulation sub-item scores of the Eating Disorder Inventory-2. These findings confirm that BN is associated with increased levels of serum lipids. This alteration may be involved in the pathophysiology of certain psychopathological characteristics of BN and cannot be explained by the co-occurrence of other psychiatric disorders.

  12. Long-term vegetarians have low oxidative stress, body fat, and cholesterol levels.

    Science.gov (United States)

    Kim, Mi Kyung; Cho, Sang Woon; Park, Yoo Kyoung

    2012-04-01

    Excessive oxidative stress and abnormal blood lipids may cause chronic diseases. This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid profiles of sex- and age-matched long-term vegetarians and omnivores in Korea. Forty-five vegetarians (23 men and 22 women; mean age, 49.5 ± 5.3 years), who had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15 men and 15 women; mean age, 48.9 ± 3.6 years) participated in this study. Their 1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was measured by the levels of diacron reactive oxygen metabolites (d-ROM). Antioxidant status was determined by the biological antioxidant potential (BAP) and levels of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. We observed that vegetarians had a significantly lower body fat percentage (21.6 ± 6.4%) than that of omnivores (25.4 ± 4.6%; P vegetarians than those in omnivores (331.82 ± 77.96 and 375.80 ± 67.26 Carratelli units; P vegetarians and omnivores were 173.73 ± 31.42 mg/dL and 193.17 ± 37.89 mg/dL, respectively (P vegetarians and omnivores, respectively, indicating that vegetarians had significantly lower lipid levels. Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term vegetarians than those in omnivores.

  13. Significant improvement in statin adherence and cholesterol levels after acute myocardial infarction

    DEFF Research Database (Denmark)

    Brogaard, Hilde Vaiva Tonstad; Køhn, Morten Ganderup; Berget, Oline Sofie

    2012-01-01

    Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time.......Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time....

  14. Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor-deficient mice

    OpenAIRE

    Peñalvo, José L.; Hopia, Anu; Adlercreutz, Herman

    2006-01-01

    Background Sesamin, a major lignan from sesame seeds has been associated with cholesterol reduction in previous reports, but recent studies suggested differences in the response to sesamin intake depending on the model studied as well as the nature of the sesamin preparation used. Aim The effect of pure sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor-knockout mice under cholesterol fed condition. Design Animals were randomly assigned to 4 groups, fed an atherog...

  15. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG;

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. SETTING: The study was conducted in the Danish general population. PARTICIPANTS: Participants included 9185 women and men aged 20-80+ yr. MAIN OUTCOME MEASURES: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic......Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g>t, T2488Tc>t, R3611) or decreases (Ivs4+171c>a, A591V, Ivs18+379a>c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  16. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, B.G.; Stene, M.C.A.

    2008-01-01

    Context Low levels of high- density lipoprotein ( HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. Objective To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss- of- function mutations in ABCA1 cause...... Study ( CGPS), a cross- sectional general population study ( n= 31 241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study ( CIHDS), a case- control study ( n= 16 623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007....... Main Outcome Measures Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype. Results Heterozygotes vs noncarriers for 4 ABCA1 mutations ( P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/ d...

  17. Cholesterol Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Cholesterol Share this page: Was this page helpful? Also known as: Blood Cholesterol Formal name: Total Cholesterol Related tests: HDL Cholesterol , ...

  18. What's Cholesterol?

    Science.gov (United States)

    ... los dientes Video: Getting an X-ray What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? Print A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  19. What's Cholesterol?

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? A A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  20. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  1. Effects of rapeseed and soybean oil dietary supplementation on bovine fat metabolism, fatty acid composition and cholesterol levels in milk.

    Science.gov (United States)

    Altenhofer, Christian; Spornraft, Melanie; Kienberger, Hermine; Rychlik, Michael; Herrmann, Julia; Meyer, Heinrich H D; Viturro, Enrique

    2014-02-01

    The main goal of this experiment was to study the effect of milk fat depression, induced by supplementing diet with plant oils, on the bovine fat metabolism, with special interest in cholesterol levels. For this purpose 39 cows were divided in three groups and fed different rations: a control group (C) without any oil supplementation and two groups with soybean oil (SO) or rapeseed oil (RO) added to the partial mixed ration (PMR). A decrease in milk fat percentage was observed in both oil feedings with a higher decrease of -1·14 % with SO than RO with -0·98 % compared with the physiological (-0·15 %) decline in the C group. There was no significant change in protein and lactose yield. The daily milk cholesterol yield was lower in both oil rations than in control ration, while the blood cholesterol level showed an opposite variation. The milk fatty acid pattern showed a highly significant decrease of over 10 % in the amount of saturated fatty acids (SFA) in both oil feedings and a highly significant increase in mono (MUFA) and poly (PUFA) unsaturated fatty acids, conjugated linoleic acids (CLA) included. The results of this experiment suggest that the feeding of oil supplements has a high impact on milk fat composition and its significance for human health, by decreasing fats with a potentially negative effect (SFA and cholesterol) while simultaneously increasing others with positive (MUFA, PUFA, CLA).

  2. Znf202 affects high density lipoprotein cholesterol levels and promotes hepatosteatosis in hyperlipidemic mice.

    Directory of Open Access Journals (Sweden)

    Carlos L J Vrins

    Full Text Available BACKGROUND: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. METHODOLOGY AND PRINCIPAL FINDINGS: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep and in bile acid synthesis (cyp7a1 were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. CONCLUSION/SIGNIFICANCE: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels.

  3. Effects of vitamin C supplementation in human volunteers with a range of cholesterol levels on biomarkers of oxygen radical-generated damage

    NARCIS (Netherlands)

    Anderson, D.; Phillips, B.J.; Yu, T-W.; Edwards, A.J.; Ayesh, R.; Butterworth, K.R.

    2000-01-01

    Twenty-four men and 24 women, all nonsmoking, and maintaining normal dietary habits were assigned to 3 groups of 16. Each group comprising 4 males with "low" cholesterol levels (<6 mmol/L) matched for age and build with 4 males with "high" cholesterol levels (>6 mmol/L) and 8 similarly matched femal

  4. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    Directory of Open Access Journals (Sweden)

    Savel J

    2012-06-01

    Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

  5. How to Get Your Cholesterol Tested

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More How To Get Your Cholesterol Tested Updated:Apr 3,2017 Cholesterol plays a ... factors for heart disease and stroke . How is cholesterol tested? A cholesterol screening measures your level of ...

  6. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

    Directory of Open Access Journals (Sweden)

    Gårevik Nina

    2012-03-01

    Full Text Available Abstract Background Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR. There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR. Methods 39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2. Results The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007. This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively. Conclusion Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.

  7. Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.

    Science.gov (United States)

    Boes, Eva; Coassin, Stefan; Kollerits, Barbara; Heid, Iris M; Kronenberg, Florian

    2009-03-01

    High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. macrophages) to the liver or other tissues. This complex process is thought to represent the basis for the antiatherogenic properties of HDL particles. The amount of cholesterol transported in HDL particles is measured as HDL cholesterol (HDLC) and is inversely correlated with the risk for coronary artery disease: an increase of 1mg/dL of HDLC levels is associated with a 2% and 3% decrease of the risk for coronary artery disease in men and women, respectively. Genetically determined conditions with high HDLC levels (e.g. familial hyperalphalipoproteinemia) often coexist with longevity, and higher HDLC levels were found among healthy elderly individuals. HDLC levels are under considerable genetic control with heritability estimates of up to 80%. The identification and characterization of genetic variants associated with HDLC concentrations can provide new insights into the background of longevity. This review provides an extended overview on the current genetic-epidemiological evidence from association studies on genes involved in HDLC metabolism. It provides a path through the jungle of association studies which are sometimes confusing due to the varying and sometimes erroneous names of genetic variants, positions and directions of associations. Furthermore, it reviews the recent findings from genome-wide association studies which have identified new genes influencing HDLC levels. The yet identified genes together explain only a small amount of less than 10% of the HDLC variance, which leaves an enormous room for further yet to be identified genetic variants. This might be accomplished by large population-based genome-wide meta-analyses and by deep-sequencing approaches on the identified genes. The resulting findings will probably result in a re-drawing and extension of

  8. Characteristics of mRNA levels of hepatic key enzymes in cholesterol metabolism of genetically gallstone-susceptible mice

    Institute of Scientific and Technical Information of China (English)

    许国强; 赵力

    2004-01-01

    @@ Our previous study1 indicated that biliary cholesterol hypersecretion was the key pathophysiological defect of gallstone formation. Lith genes determine biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice.

  9. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  10. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  11. HDL cholesterol levels are an important factor for determining the lifespan of erythrocytes

    NARCIS (Netherlands)

    Meurs, I.; Hoekstra, M; van Wanrooij, EJA; Hildebrand, RB; Kuiper, J; Kuipers, F; Hardeman, MR; Van Berkel, TJC; Van Eck, M

    2005-01-01

    Objective. Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also deve

  12. Fasting serum triglyceride and high-density lipoprotein cholesterol levels in patients intended to be treated for dyslipidemia

    Directory of Open Access Journals (Sweden)

    Genovefa D Kolovou

    2005-07-01

    Full Text Available Genovefa D Kolovou1, Katherine Anagnostopoulou1, Nektarios D Pilatis1, Klelia D Salpea1, Ioannis S Hoursalas1, Ilias Petropoulos1, Helen I Bilianou2, Dennis V Cokkinos11Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece; 2Cardiology Department, Tzanio State Hospital, Piraeus, GreeceObjective: The aim of the present investigation was to evaluate the influence of serum triglycerides (TG on other plasma lipids in patients to be treated for dyslipidemia.Methodology: Lipid profiles of a cohort of 801 patients (487 males and 314 females aged 57 ± 9 years (mean ± SD were evaluated. Patients were stratified according to their plasma lipid levels. They were divided into various groups on the basis of serum TG (≥ 150 or < 150 mg/dL and high-density lipoprotein cholesterol (HDL-C (≥ 40 or < 40 mg/dL.Results: Patients with TG ≥ 150 mg/dL had a higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dL, (p < 0.001. Patients with HDL-C < 40 mg/dL had a lower serum total cholesterol and higher TG compared with those with HDL-C ≥ 40 mg/dL (p = 0.011 and p < 0.0001, respectively. In all patients as well as in the subgroups, an inverse correlation between TG and HDL-C was found (r = –0.377, p < 0.001.Conclusions: Although, the metabolic pathway for TG and HDL-C is closely linked, an inverse correlation between TG and HDL-C levels seems to exist in the entire sampled population. This correlation also appears to persist in fasting patients with low levels of TG.Keywords: triglycerides, high-density lipoprotein cholesterol, dyslipidemia

  13. Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals

    NARCIS (Netherlands)

    Hofman, M.K.; Groenendijk, M.; Verkuijlen, P.J.J.H.; Jonkers, I.J.A.M.; Mohrschladt, M.F.; Smelt, A.H.M.; Princen, H.M.G.

    2004-01-01

    The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). An A to C substitution 278 bp upstream in the promoter of the CYP7A1 gene was found to be associated with variations in serum lipid levels in normolipidaemic populations. In the pres

  14. Effect of monounsaturated fatty acids on high-density and low-density lipoprotein cholesterol levels and blood pressure in healthy men and women.

    NARCIS (Netherlands)

    Mensink, R.P.

    1990-01-01

    The purpose of the studies described in this thesis was to examine the effect of monounsaturated fatty acids on the distribution of serum cholesterol over high-density and low-density lipoproteins (HDL and LDL) and on blood pressure in healthy men and women. High levels of LDL cholesterol and bl

  15. An overview on therapeutics attenuating amyloid β level in Alzheimer's disease: targeting neurotransmission, inflammation, oxidative stress and enhanced cholesterol levels.

    Science.gov (United States)

    Zhou, Xiaoling; Li, Yifei; Shi, Xiaozhe; Ma, Chun

    2016-01-01

    Alzheimer's disease (AD) is the most common underlying cause of dementia, and novel drugs for its treatment are needed. Of the different theories explaining the development and progression of AD, "amyloid hypothesis" is the most supported by experimental data. This hypothesis states that the cleavage of amyloid precursor protein (APP) leads to the formation of amyloid beta (Aβ) peptides that congregate with formation and deposition of Aβ plaques in the frontal cortex and hippocampus. Risk factors including neurotransmitter modulation, chronic inflammation, metal-induced oxidative stress and elevated cholesterol levels are key contributors to the disease progress. Current therapeutic strategies abating AD progression are primarily based on anti-acetylcholinesterase (AChE) inhibitors as cognitive enhancers. The AChE inhibitor, donepezil, is proven to strengthen cognitive functions and appears effective in treating moderate to severe AD patients. N-Methyl-D-aspartate receptor antagonist, memantine, is also useful, and its combination with donepezil demonstrated a strong stabilizing effect in clinical studies on AD. Nonsteroidal anti-inflammatory drugs delayed the onset and progression of AD and attenuated cognitive dysfunction. Based upon epidemiological evidence and animal studies, antioxidants emerged as potential AD preventive agents; however, clinical trials revealed inconsistencies. Pharmacokinetic and pharmacodynamic profiling demonstrated pleiotropic functions of the hypolipidemic class of drugs, statins, potentially contributing towards the prevention of AD. In addition, targeting the APP processing pathways, stimulating neuroprotective signaling mechanisms, using the amyloid anti-aggregants and Aβ immunotherapy surfaced as well-tested strategies in reducing the AD-like pathology. Overall, this review covers mechanism of inducing the Aβ formation, key risk factors and major therapeutics prevalent in the AD treatment nowadays. It also delineates the need

  16. An antibody against the C-terminal domain of PCSK9 lowers LDL cholesterol levels in vivo.

    Science.gov (United States)

    Schiele, Felix; Park, John; Redemann, Norbert; Luippold, Gerd; Nar, Herbert

    2014-02-20

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease. The inhibition of PCSK9 function by therapeutic antibodies that block interaction of PCSK9 with the epidermal growth factor-like repeat A domain of LDL receptor (LDLR) was shown to successfully lower LDL cholesterol levels in clinical studies. Here we present data on the identification, structural and biophysical characterization and in vitro and in vivo pharmacology of a PCSK9 antibody (mAb1). The X-ray structure shows that mAb1 binds the module 1 of the C-terminal domain (CTD) of PCSK9. It blocks access to an area bearing several naturally occurring gain-of-function and loss-of-function mutations. Although the antibody does not inhibit binding of PCSK9 to epidermal growth factor-like repeat A, it partially reverses PCSK9-induced reduction of the LDLR and LDL cholesterol uptake in a cellular assay. mAb1 is also effective in lowering serum levels of LDL cholesterol in cynomolgus monkeys in vivo. Complete loss of PCSK9 is associated with insufficient liver regeneration and increased risk of hepatitis C infections. Blocking of the CTD is sufficient to partially inhibit PCSK9 function. Antibodies binding the CTD of PCSK9 may thus be advantageous in patients that do not tolerate complete inhibition of PCSK9.

  17. About Cholesterol

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Cholesterol Updated:Apr 3,2017 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  18. A Review on Effects of Probiotic Supplementation in Poultry Performance and Cholesterol Levels of Egg and Meat

    Directory of Open Access Journals (Sweden)

    Tarekegn Getachew

    2016-03-01

    Full Text Available Probiotics are live microbial food/feed ingredients that have a beneficial effect on health that stimulates the growth of beneficial microorganisms and reduces the amount of pathogens, thus improving the intestinal microbial balance of the host and lowering the risk of gastro-intestinal diseases. Probiotics can be harmful to debilitated and immuno-compromised populations. An accurate dosage of administration has yet to be established despite the wide-use of probiotics. Probiotics have antimutagenic, anticarcinogenic, hypocholesterolemic, antihypertensive, anti-osteoporosis, and immunomodulatory effects. Lactobacillus, Bifidobacterium, Leuconostoc, Enterococcus, Lactococcus, Bacillus, Saccharomyces, Aspergillus and Pediococcus species are most commonly used probiotics in poultry production. When supplemented to chicken probiotics improve feed-intake, growth performance, meat quality, egg production, egg quality and have cholesterol lowering potential in poultry products. However, some studies reported no significant effect of probiotics on feed-intake, production traits, products’ quality and cholesterol level.

  19. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease.

    Science.gov (United States)

    Huang, Xuemei; Chen, Honglei; Miller, William C; Mailman, Richard B; Woodard, Jennifer L; Chen, Peter C; Xiang, Dong; Murrow, Richard W; Wang, Yi-Zhe; Poole, Charles

    2007-02-15

    The apolipoprotein E (APOE) epsilon2 allele has been associated with both Parkinson's disease (PD) and lower low-density lipoprotein cholesterol (LDL-C). We tested the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 112 controls. The PD cases were recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and the controls were recruited from the spouse populations of the same clinic. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterol-lowering agents. Lower LDL-C concentrations were associated with a higher occurrence of PD. Compared with participants with the highest LDL-C (> or =138 mg/dL), the OR was 2.2 (95% CI = 0.9-5.1) for participants with LDL-C of 115 to 137, 3.5 (95% CI = 1.6-8.1) for LDL-C of 93 to 114, and 2.6 (95% CI = 1.1-5.9) for LDL-C of < or = 92. Interestingly, use of either cholesterol-lowering drugs, or statins alone, was related to lower PD occurrence. Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation.

  20. Serum total cholesterol level and some cancer mortality:A 7 years follow-up study in 698796 people

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qin-feng; WU Duo-wen; Jong Ku Park; Sang Baek Koh; Chun Bae Kim; Sei Jin Chan

    2003-01-01

    were lung cancer during the follow up period. Meanwhile serum total cholesterol levels were inversely and significantly related to overall cancer and liver cancer mortality in population, in both male and female. Overall cancer and liver cancer mortality decreased with increasing cholesterol levels at the lowest levels in both gender. This effect is still apparent when deaths within three years are excluded in population and male. A weak inverse association between cholesterol and stomach cancer. This is not significant for cholesterol and lung cancer. Conclusion: There is important relation between lower serum cholesterol increased the risk of overall cancer and liver cancer mortality. Low serum cholesterol concentration as predictor of overall cancer and liver cancer is importance in both genders.

  1. Association between apolipoprotein E promoter-219G/T polymorphism and total cholesterol level in patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    Fang Liu; Xiao Sun; Jing Wang; Yan Kong; Li Cui; Xiangdang Shi

    2006-01-01

    BACKGROUND: Many researches have suggested that apolipoprotein E (APOE) and total cholesterol metabolism are closely related with dementia. In the supposed theory, 219 site of APOE promoter region is near gene coding region, so its polymorphism may result in the abnormality of APOE gene and protein expression,and finally lead to dementia.OBJECTIVE: To observe the association between APOE promoter-219G/T polymorphisms with serum total cholesterol in patients with Alzheimer disease, and compare it with non-dementia people.DESIGN: Case-control, comparative observation.SETTING: Department of Neurology, Fengtian Hospital of Shenyang Medical College.PARTICIPANTS: Fifty-five dementia patients including 27 males and 28 females aged (66±3) years and treated in the Department of Neurology, Fengtian Hospital were selected from January 2002 to December 2005 as the Alzheimer disease group. They all diagnosed according to the DSM- Ⅳ diagnostic criteria of Alzheimer disease instituted by American Psychiatry Association in 1994. Meanwhile, 44 none-dementia patients including 21 males and 23 females aged (66±3) years were selected from other clinical departments of Fengtian Hospital as control group. All the participants were informed the detection and agreed.METHODS: Genomic DNA was extracted from the peripheral blood of all subjects, then "NEST"PCR, DNA sequence and enzyme digestion were adopted to detect the expression of APOE promoter-219 polymorphism,following by biomedical statistics analysis based on the clinical total cholesterol level.MAIN OUTCOME MEASURES: Polymorphism of APOEpromoter-219 G/T and total cholesterol level.RESULTS: All 55 dementia patients and 44 non-dementia ones were involved in the result analysis. ①Allele and genotype frequency: The T allele frequency of the Alzheimer disease group was significantly higher than that in the control group [88.2% (97/110), 54.5% (48/88)], while G allele frequency was remarkably lower than that in the control group [11

  2. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  3. Relationship between expression of CD40-CD40 ligand system and serum cholesterol levels in patients with hypercholesterolemia

    Institute of Scientific and Technical Information of China (English)

    严金川; 吴宗贵; 李莉; 仲人前; 孔宪涛

    2004-01-01

    @@ Hypercholesterolemia is associated with the pathogenesis of atherosclerosis. Enhanced levels of thrombin, fibrinogen and factor Ⅶc directly correlate with cholesterol levels.1 Activated platelets adhere to the intact endothelium and induce inflammatory responses in the endothelium, which substantially contribute to the early phase of atherosclerosis. Emerging lines of evidence support the role of CD40-CD40L interactions in atherosclerosis, thrombosis and inflammation.2 In atherosclerosis, inhibition of the CD40-CD40L interaction in LDL receptors or ApoE-deficient mice prevents the initiation of atherosclerosis and the evolvement of established atherosclerotic lesions to more advanced lesions.

  4. Effects of Kluyveromyces marxianus Isolated from Tibetan Mushrooms on the Plasma Lipids, Egg Cholesterol Level, Egg Quality and Intestinal Health of Laying Hens

    Directory of Open Access Journals (Sweden)

    S Zhong

    Full Text Available ABSTRACT The effects of the Kluyveromyces marxianus M3 strain, isolated from Tibetan mushrooms, on plasma lipids, egg cholesterol level, egg quality, and intestinal health of laying hens were evaluated. In total, 160 Beijing fatty laying hens (43 weeks old were divided into four groups and fed a basal diet supplemented with 0%, 0.1%, 0.3%, or 0.5% freeze-dried K. marxianus M3 powder for four weeks. The results showed that yeast supplementation reduced serum total cholesterol (TC, triglyceride (TG, low density lipoprotein-cholesterol (LDL-C, and very low density lipoprotein-cholesterol (VLDL-C levels (p<0.01, and increased serum high density lipoprotein-cholesterol (HDL-C level (p<0.05. Moreover, regardless of K. marxianus M3 dietary addition level, the cholesterol content of the eggs decreased by more than 26%. When0.3% yeast was supplemented, significant differences were found in the egg weights, shell strength, albumen height, Haugh unit and nutrient content of the eggs (p<0.01. Finally, 0.3% yeast supplementation improved the intestinal flora conditions of the hens by decreasing the Salmonella and Staphylococcus aureus counts (p<0.01 and increasing the Bifidobacterium count (p<0.01. The results in this work demonstrated that yeast culture supplementation to the diets deceased the serum and egg yolk cholesterol, and increased egg quality.

  5. Spirulina platensis effects on the levels of total cholesterol, HDL and triacylglycerols in rabbits fed with a hypercholesterolemic diet

    Directory of Open Access Journals (Sweden)

    Luciane Maria Colla

    2008-04-01

    Full Text Available In this work, hypercholesterolemia was induced in rabbits by feeding them a high cholesterol diet (CD, 350 mg/d and the effects of supplementing this diet with 0.5 g/d Spirulina platensis was evaluated by measuring the levels of serum total-cholesterol (TC, triacylglycerols (TAG and high-density lipoprotein (HDL-cholesterol at the start of the experiment and after 30 d and 60 d. It was found that the levels of serum cholesterol decreased from 1,054±101 mg.dL-1 in the rabbits fed a CD without S. platensis to 516±163 mg.dL-1 to those fed with a high cholesterol diet supplemented with S. platensis (significant at p A microalga Spirulina é cultivada e comercializada no mundo devido a suas características nutricionais (elevada concentração de proteínas, em torno de 65%, vitaminas e sais minerais e ao seu potencial terapêutico no tratamento de inúmeras doenças, inclusive a hipercolesterolemia. Neste trabalho foi avaliada a inibição da hipercolesterolemia induzida em coelhos por uma dieta adicionada de colesterol (350 mg.d-1, pela suplementação de 0,5 g.dia-1 de biomassa de Spirulina platensis, sendo avaliados os níveis de colesterol total, triglicerídeos e HDL nos tempos de 0 d, 30 d e 60 d de tratamento. Os resultados indicaram que a adição de Spirulina platensis na dieta ocasionou decréscimo nos níveis de colesterol total de 1054±101 mg.dL-1 para 516±163 mg.dL-1 (p<0,0001, para os coelhos alimentados com a dieta colesterolêmica em comparação com os que receberam a dieta adicionada de Spirulina platensis. A adição de Spirulina a dieta colesterolêmica não ocasionou decréscimo significativo nos níveis de triglicerídios dos coelhos. Os valores de HDL aumentaram de 73±31 mg.dL-1 para 91,0±15,7 mg.dL-1, comparando-se os coelhos alimentados com a dieta colesterolêmica e os alimentados com a dieta adicionada de Spirulina, estatisticamente diferentes a um nível de significância maior que 0,1533.

  6. Lower low density lipid cholesterol levels are associated with Parkinson’s disease

    OpenAIRE

    Huang, Xuemei; Chen, Honglei; Miller, William C.; Mailman, Richard B.; Woodard, Jennifer L.; Chen, Peter C.; Xiang, Dong; Murrow, Richard W.; Wang, Yi-Zhe; Poole, Charles

    2007-01-01

    The apolipoprotein E (APOE) ε2 allele has been associated with both Parkinson’s disease (PD) and lower low density lipoprotein cholesterol (LDL-C). The study is to test the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 110 controls, the PD cases recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and controls recruited from the spouse populations of the same clinic. Mu...

  7. A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes

    Institute of Scientific and Technical Information of China (English)

    高峰; 严同; 赵艳; 尹凡; 胡翠宁

    2010-01-01

    This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco's modified Eagle's medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRN...

  8. In situ probing of cholesterol in astrocytes at the single-cell level using laser desorption ionization mass spectrometric imaging with colloidal silver.

    Science.gov (United States)

    Perdian, D C; Cha, Sangwon; Oh, Jisun; Sakaguchi, Donald S; Yeung, Edward S; Lee, Young Jin

    2010-04-30

    Mass spectrometric imaging has been utilized to localize individual astrocytes and to obtain cholesterol populations at the single-cell level in laser desorption ionization (LDI) with colloidal silver. The silver ion adduct of membrane-bound cholesterol was monitored to detect individual cells. Good correlation between mass spectrometric and optical images at different cell densities indicates the ability to perform single-cell studies of cholesterol abundance. The feasibility of quantification is confirmed by the agreement between the LDI-MS ion signals and the results from a traditional enzymatic fluorometric assay. We propose that this approach could be an effective tool to study chemical populations at the cellular level.

  9. The Expression of Estrogen Receptor is Dependent on the Estrogen Level and Associated with Cholesterol-Rich Diet in Female Rat's Heart and Vascular Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    吴赛珠; 刘建国; 周可祥; 刘长青; 马瑞; 孙飞; 隗和明

    2003-01-01

    Objective To study the effects of estrogen level and cholesterol - rich diet on the ex-pression of estrogen receptor (ER) in cardiovasculartissues including vascular endothelial cells (VEC) offemale rats. Methods The receptor binding assay(RBA) was adopted to measure the estrogen receptorlevel in aortic wall, heart and vascular endothelialcells of female rats on a cholesterol- rich diet. A ra-dioimmunoassay was employed to measure the level ofserum estradiol. Results The number of ER signif-icantly decreased in hearts, aorta and vascular en-dothelial cells in the ovariectomized rats and the ratson a cholesterol- rich diet. In contrast, the adminis-tration of estrogen somewhat restored the expression ofER. Conclusions For female rats, the level of es-trogen affects the expression of ER in cardiovascularsystem. The number of ER decreases along with thedecrease in the level of estrogen. A cholesterol -richdiet also can decrease the expression of ER in cardio-vascular system of female rats.

  10. Association of total cholesterol and HDL-C levels and outcome in coronary heart disease patients with heart failure

    Science.gov (United States)

    Zhao, Qin; Li, Jianfei; Yang, Jin; Li, Rongshan

    2017-01-01

    Abstract The aim of the study was to evaluate associations of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels with prognosis in coronary heart disease (CHD) patients with heart failure (HF). Patients who were angiographical-diagnosis of CHD and echocardiographical-diagnosis of left ventricular ejection fraction (LVEF) Hs-CRP) was observed. TC was positively correlated with BMI and albumin, and HDL-C was inversely correlated with Hs-CRP. The associations of TC level and rehospitalization for HF and all-cause mortality were attenuated but consistently significant through model 1 to 4, with odds ratio (OR) of 0.97 (95% confidence interval [CI]: 0.92–0.99). Associations of HDL-C level and rehospitalization for HF and all-cause mortality were also consistently significant through model 1 to 4, with OR of 0.95 (95% CI: 0.90–0.98). Strength of association was attenuated prominently in model 3 after adjusted for Hs-CRP, and no change was observed after further adjusted for BMI and albumin. Higher baseline TC and HDL-C levels are associated with better outcome in CHD patients with HF. PMID:28248864

  11. Amyloid Beta Peptides Affect Pregnenolone and Pregnenolone Sulfate Levels in PC-12 and SH-SY5Y Cells Depending on Cholesterol.

    Science.gov (United States)

    Calan, Ozlem Gursoy; Akan, Pinar; Cataler, Aysenur; Dogan, Cumhur; Kocturk, Semra

    2016-07-01

    Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25-35, AB 1-40 and AB 1-42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose-and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25-35 were higher than those in AB 1-40 and AB 1-42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase

  12. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Petroula Proitsi

    2014-09-01

    Full Text Available Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578. We constructed weighted genotype risk scores (GRSs for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013. Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol. Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.Genetic predisposition to increased blood cholesterol and

  13. Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

    Science.gov (United States)

    Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori

    2015-03-01

    No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population.

  14. Effects of dietary garlic powder and {alpha}-tocopherol supplementation on performance, serum cholesterol levels, and meat quality of chicken.

    Science.gov (United States)

    Choi, I H; Park, W Y; Kim, Y J

    2010-08-01

    This study was carried out to evaluate the effects of supplementing diets with garlic powder and alpha-tocopherol on performance, serum cholesterol levels, and meat quality of chickens. Three hundred 1-d-old male broiler chicks were assigned to 5 diet treatments (0, 1, 3, and 5% garlic powder and 3% garlic powder + 200 IU of alpha-tocopherol/kg) with 3 replications of 20 birds for 35 d. There were no significant differences in broiler performance among the treatments. Moisture and crude ash contents of chicken thigh muscle were not different among all treatments, but dietary garlic powder and alpha-tocopherol supplementation resulted in significantly higher CP and lower crude fat contents in comparison with control (P garlic powder and applying garlic powder plus alpha-tocopherol significantly decreased total and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol in broiler blood (P garlic powder and alpha-tocopherol. However, no significant differences in water-holding capacity or shear force values were observed among the treatments. For broiler thigh muscle color, L* (lightness) values were decreased (P garlic powder levels and the combination of garlic powder and alpha-tocopherol. In terms of fatty acid composition in thigh muscle, unlike saturated fatty acid and total saturated fatty acid, dietary garlic powder or garlic powder plus alpha-tocopherol supplementation increased unsaturated fatty acid, total unsaturated fatty acid, and total unsaturated fatty acid:total saturated fatty acid ratios. These results suggest that 5% garlic powder or 3% garlic powder plus 200 IU of alpha-tocopherol antioxidant properties were effective for enhancing lipid and color stability.

  15. Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level

    Directory of Open Access Journals (Sweden)

    Nogueira Juan-Patricio

    2012-03-01

    Full Text Available Abstract Background Low plasma high-density lipoprotein-cholesterol (HDL-c level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin in subsets of class II and III obese patients. Methods Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin, unacylated ghrelin, body composition (DXA and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO without metabolic syndrome, compared to 21 healthy lean control subjects. Results Insulin resistance (HOMA-IR increased gradually from MHO to LHO and from LHO to MAO patients (p p = 0.032. Conclusions These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.

  16. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    OpenAIRE

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Ameri...

  17. Alpinia zerumbet potentially elevates high-density lipoprotein cholesterol level in hamsters.

    Science.gov (United States)

    Lin, Li-Yun; Peng, Chiung-Chi; Liang, Yu-Jing; Yeh, Wan-Ting; Wang, Hui-Er; Yu, Tung-Hsi; Peng, Robert Y

    2008-06-25

    In folkloric plant medicines, Alpinia zerumbet (AZ) has been popularly recognized as an exellent hepatoprotector. To search for a good high-density lipoprotein cholesterol (HDL-C) elevating herbal preparation, we examined AZ for its antioxidant and hypolipidaemic bioactivities, especially its HDL-C elevating activity. AZ seeds contain 0.51% essential oils (SO), which are comprised of monoterpenoids, oxygenated monoterpenoids, sesquiterpenoids, oxygenated sesquiterpenoids, aldehydes, acid, and esters. Gas chromatography/mass spectrometry analysis indicated that most of the monoterpenes and sesquiterpenes were recoverable in pentane eluent, whilst the oxygenated monoterpenoids and sesquiterpenoids remained in ether eluent. The high contents of rutin, quercetin, and polyphenolics in ethanolic extract of AZ seeds exhibit moderate antilipoperoxidative but potent DPPH free radical scavenging bioactivities. Conclusively, both seed powder (SP) and SO are effective hypolipidaemics with amazingly potent HDL-C elevating capabilities. On the basis of hepatoprotectivity, SP is a more feasible hypolipidemic agent as well as a promising HDL-C elevating plant medicine.

  18. Predicting survival of endoscopic gastrostomy candidates using the underlying disease, serum cholesterol, albumin and transferrin levels

    Directory of Open Access Journals (Sweden)

    Jorge Fonseca

    2013-08-01

    Full Text Available Background: Endoscopic gastrostomy (PEG is the gold standard for long-term enteral feeding. An adequate PEG candidate must have life expectancy longer than a few weeks. Patients surviving less than three weeks should have a nasogastric tube, and gastrostomy should be avoid. There are few studies looking to prognostic factors and fewer attempts of creating a predictor model for PEG patient's survival. Aim: The aim of this study was creating a predictive survival model for PEG candidates, using underlying disease, cholesterol, albumin and transferrin. Methods: Data was obtained from records of adult patients that underwent PEG between 1999 and 2011. Patients surviving 3 weeks were considered adequate survivors. A full logistic regression model was used to classify future cases into one of the two groups of survival. Results: An equation for the probability of future cases was generated, in order to obtain a P value. In the future, patients with a P > 0,88 will have a 64,7% probability of adequate surviving; patients with a P < 0,88 will have a 70.3% probability of short surviving. Conclusions: When clinical evaluation alone does not display a clear prognosis, this equation should be included in the evaluation of gastrostomy candidates, avoiding useless gastrostomy.

  19. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  20. Omega-3 Fatty Acid Enriched Chevon (Goat Meat Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

    Directory of Open Access Journals (Sweden)

    Mahdi Ebrahimi

    2014-01-01

    Full Text Available In this study, control chevon (goat meat and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n=10 in each group for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P<0.05 in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

  1. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  2. Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

    Science.gov (United States)

    Molin, G; Andersson, R; Ahrné, S; Lönner, C; Marklinder, I; Johansson, M L; Jeppsson, B; Bengmark, S

    1992-04-01

    Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA.

  3. Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

    DEFF Research Database (Denmark)

    Moghimi, S.M.; Hamad, I.; Bunger, R.;

    2006-01-01

    Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed...

  4. Low density lipoprotein cholesterol level inversely correlated with coronary flow velocity reserve in patients with Type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Jie Yu; Jiang-Li Han; Li-Yun He; Xin-Heng Feng; Wei-Hong Li; Jie-Ming Mao; Wei Gao; Guang Wang

    2013-01-01

    Objectives To evaluate the association of coronary artery endothelial function and plasma levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in patients with Type 2 Diabetes Mellitus (DM). Methods We investigated 90 participants from our institution between October 2007 to March 2010: non-DM (n = 60) and DM (n = 30). As an indicator of coronary endothelial dysfunction, we used non-invasive Doppler echocardiography to quantify coronary flow velocity reserve (CFVR) in the distal part of the left descending artery after rest and after intravenous adenosine administration. Results Plasma level of LDL-C was significantly higher in patients with DM than in non-DM (3.21 0.64 vs. 2.86 0.72 mmo/L, P < 0.05), but HDL-C level did not differ between the groups (1.01 0.17 vs. 1.05 0.19 mmo/L). Furthermore, the CFVR value was lower in DM patients than non-diabetics (2.45±0.62 vs. 2.98±0.68, P < 0.001). Plasma levels of LDL-C were negatively correlated with CFVR in all subjects (r = 0.35, P < 0.001; 95% confidence interval (CI): 0.52 -C0.15) and in the non-DM (r = 0.29, P < 0.05; 95% CI: 0.51–0.05), with an even stronger negative correlation in the DM group (r = 0.42, P < 0.05; 95% CI: 0.68 –0.06). Age (β = 0.019, s = 0.007, sβ = 0.435, 95% CI: 0.033 –0.005, P = 0.008), LDL-C (β = 0.217, s = 0.105, sβ = 0.282, 95% CI: 0.428 –0.005, P = 0.045) remained independently correlated with CFVR in the DM group. However, we found no correlation between HDL-C level and CFVR in any group. Conclusions Diabetes may contribute to coronary artery disease (CAD) by inducing dysfunction of the coronary artery endothelium. Increased LDL-C level may adversely impair coronary endothelial function in DM. HDL-C may lose its endothelial-protective effects, in part as a result of pathological conditions, especially under abnormal glucose metabolism.

  5. Effect of Animal and Industrial Trans Fatty Acids on HDL and LDL Cholesterol Levels in Humans - A Quantitative Review

    NARCIS (Netherlands)

    Brouwer, I.A.; Wanders, A.J.; Katan, M.B.

    2010-01-01

    Background: Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid an

  6. Cholesterol transport in model membranes

    Science.gov (United States)

    Garg, Sumit; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula

    2010-03-01

    Physiological processes distribute cholesterol unevenly within the cell. The levels of cholesterol are maintained by intracellular transport and a disruption in the cell's ability to keep these normal levels will lead to disease. Exchange rates of cholesterol are generally studied in model systems using labeled lipid vesicles. Initially donor vesicles have all the cholesterol and acceptor vesicles are devoid of it. They are mixed and after some time the vesicles are separated and cholesterol is traced in each vesicle. The studies performed up to date have significant scatter indicating that the methodologies are not consistent. The present work shows in-situ Time-Resolved SANS studies of cholesterol exchange rates in unsaturated PC lipid vesicles. Molecular dynamics simulations were done to investigate the energetic and kinetic behavior of cholesterol in this system. This synergistic approach will provide insight into our efforts to understand cholesterol traffic.

  7. CORRELATION OF BREAST CANCER AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL: A SINGLE CENTRE STUDY

    Directory of Open Access Journals (Sweden)

    Anjali

    2015-12-01

    Full Text Available Breast cancer is the most common site specific cancer in women. Lots of etiological factors have been suggested regarding its causation. The risk is influenced by obesity, parity, exogenous and endogenous hormones, exposure to chemicals and radiation and many more. Various studies suggest that as HDL-C seems to be cardio protective, it is also protective for breast cancer. Serum HDL-C levels are found to be low in breast cancer patients. We studied this hypothesis in local population of Southern Rajasthan and nearby region to see if low serum HDL-C is associated with increased risk of breast cancer. We studied serum HDL-C level in 50 female patients of breast cancer along with their menopausal status and compared it to their respective controls. We found that breast cancer patients had significantly low level of serum HDL-C and presented in advanced stage of cancer. It supports that low serum HDL-C level is associated with increased risk of breast cancer. So one should think about those dietary and lifestyle measures, which maintain high serum HDL-C level so that it might become preventive measure for breast cancer.

  8. Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels.

    Directory of Open Access Journals (Sweden)

    Wilmar Igl

    2010-01-01

    Full Text Available Genome-wide association studies (GWAS have identified 38 larger genetic regions affecting classical blood lipid levels without adjusting for important environmental influences. We modeled diet and physical activity in a GWAS in order to identify novel loci affecting total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. The Swedish (SE EUROSPAN cohort (N(SE = 656 was screened for candidate genes and the non-Swedish (NS EUROSPAN cohorts (N(NS = 3,282 were used for replication. In total, 3 SNPs were associated in the Swedish sample and were replicated in the non-Swedish cohorts. While SNP rs1532624 was a replication of the previously published association between CETP and HDL cholesterol, the other two were novel findings. For the latter SNPs, the p-value for association was substantially improved by inclusion of environmental covariates: SNP rs5400 (p(SE,unadjusted = 3.6 x 10(-5, p(SE,adjusted = 2.2 x 10(-6, p(NS,unadjusted = 0.047 in the SLC2A2 (Glucose transporter type 2 and rs2000999 (p(SE,unadjusted = 1.1 x 10(-3, p(SE,adjusted = 3.8 x 10(-4, p(NS,unadjusted = 0.035 in the HP gene (Haptoglobin-related protein precursor. Both showed evidence of association with total cholesterol. These results demonstrate that inclusion of important environmental factors in the analysis model can reveal new genetic susceptibility loci.

  9. Cholesterol excretion and colon cancer.

    Science.gov (United States)

    Broitman, S A

    1981-09-01

    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  10. Good vs. Bad Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Good vs. Bad Cholesterol Updated:Apr 3,2017 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...

  11. High Blood Cholesterol

    Science.gov (United States)

    ... version of this page please turn Javascript on. High Blood Cholesterol What is High Blood Cholesterol? What is Cholesterol? Cholesterol is a ... heart disease. If Your Blood Cholesterol Is Too High Too much cholesterol in your blood is called ...

  12. Effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice with and without the influence of fenofibrate.

    Science.gov (United States)

    Pan, Si-Yuan; Dong, Hang; Guo, Bao-Feng; Zhang, Yi; Yu, Zhi-Ling; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming

    2011-06-01

    Schisandrin B, an active ingredient isolated from the fruit of Schisandra chinensis, increased serum and hepatic triglyceride levels in mice. In the present study, the effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice without and with the influence of fenofibrate were investigated. Parameters on hepatic index (the ratio of liver weight to body weight × 100) were also analyzed. Mice were intragastrically treated with schisandrin B at a single dose of 0.2, 0.4, 0.8, or 1.6 g/kg, without or with fenofibrate pretreatment (0.1 g/kg/day for 4 days, p.o.). Twenty-four hours after schisandrin B treatment, serum/hepatic triglyceride and total cholesterol levels were measured. Schisandrin B treatment dose-dependently increased serum and hepatic triglyceride levels as well as hepatic index in mice. In contrast, hepatic total cholesterol levels were decreased in a dose-dependent manner in schisandrin B-treated mice. Data obtained from effective kinetics analysis indicated that the action of schisandrin B on serum triglyceride had a higher specificity than those on hepatic total cholesterol and hepatic index. While fenofibrate pretreatment inhibited the schisandrin B-induced elevation in serum triglyceride levels, it completely abrogated the elevation of hepatic triglyceride levels in schisandrin B-treated mice. The combined treatment with schisandrin B and fenofibrate decreased hepatic total cholesterol level and increased the hepatic index in an additive or semi-additive manner, respectively. In conclusion, the results of effective kinetics analysis indicated that the schisandrin B-induced hypertriglyceridemia was competitively inhibited by fenofibrate. Schisandrin B may offer the prospect of setting up a mouse model of hypertriglyceridemia and fatty liver for screening triglyceride-lowering drug candidates.

  13. Characterization of vitamin E and total cholesterol levels in meat of lamb produced in the south of Sonora State, México by HPLC

    Directory of Open Access Journals (Sweden)

    María Isabel Cruz

    2013-06-01

    Full Text Available The higher cholesterol content in some meat species has been associated in many scientific papers with degenerative and cardiovascular illness. Nonetheless, there are no specific studies on Sonora’s lamb meat vitamin E and cholesterol content. The use of analytical techniques to determinate meat quality and healthiness are important as routine food analysis. The objective of this work was to characterize cholesterol and vitamin E levels in lamb meat produced in Sonora using high pressure liquid chromatography (HPLC as a precise analytical technique. Samples (15 from criollo race Longissimus dorsi muscle, 35-40 kg live weight produced in a stabled system feed with corn was lyophilized to determinate -tocopherol and cholesterol via HPLC. Results shown that the average concentration were 2.3±1.06 mg/mL and 135.62±31.4 mg/mL in 100 g of meat for α-tocopherol and cholesterol, respectively. The characterization of these analites is important to provide the necessary purchase information to consumer, increasing lamb meat added value.

  14. Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level.

    Science.gov (United States)

    Fendler, Wojciech; Rizzo, Manfredi; Borowiec, Maciej; Malachowska, Beata; Antosik, Karolina; Szadkowska, Agnieszka; Banach, Maciej; Urbanska-Kosinska, Malgorzata; Szopa, Magdalena; Malecki, Maciej; Mlynarski, Wojciech

    2014-08-01

    Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint(©) system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene-gene or gene-environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.

  15. Effect of tomato consumption on high-density lipoprotein cholesterol level: a randomized, single-blinded, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Cuevas-Ramos D

    2013-07-01

    Full Text Available Daniel Cuevas-Ramos,1 Paloma Almeda-Valdés,1 Emma Chávez-Manzanera,1 Clara Elena Meza-Arana,2 Griselda Brito-Córdova,1 Roopa Mehta,1 Oscar Pérez-Méndez,3 Francisco J Gómez-Pérez1 1Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 3Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico Introduction: Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C. This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels. Subject and methods: We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men 40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P > 0.0001. Conclusion: Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women. Keywords: lycopene, hypoalphalipoproteinemia, dyslipidemia, overweight, cardiovascular diseases

  16. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

    OpenAIRE

    2012-01-01

    Abstract Background Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR). There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the e...

  17. Common and rare alleles in apolipoprotein B contribute to plasma levels of low-density lipoprotein cholesterol in the general population

    DEFF Research Database (Denmark)

    Benn, M.; Stene, Maria Charlotte Aslaug; Nordestgaard, Børge;

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. Objective: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. Design......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. Setting: The study was conducted in the Danish general population. Participants: Participants included 9185 women and men aged 20-80+ yr. Main Outcome Measures: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic...... (0.21), R3611Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g > t, T2488Tc > t, R3611) or decreases (Ivs4 + 171c > a, A591V, Ivs18 + 379a > c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  18. Associations between apolipoprotein E genotypes and serum levels of glucose, cholesterol, and triglycerides in a cognitively normal aging Han Chinese population

    Directory of Open Access Journals (Sweden)

    Tao QQ

    2014-07-01

    Full Text Available Qing-Qing Tao,1,* Yan Chen,2,3,* Zhi-Jun Liu,1 Yi-Min Sun,1 Ping Yang,1 Shen-Ji Lu,1 Miao Xu,1 Qin-Yun Dong,1 Jia-Jun Yang,2 Zhi-Ying Wu11Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 2Department of Neurology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 3Department of Medicine, Shanghai Fengxian District Central Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: To determine the associations between apolipoprotein E (APOE genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population.Methods: There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1 E2/2 or E2/3 (APOE E2; (2 E3/3 (APOE E3; and (3 E2/4, E3/4, or E4/4 (APOE E4. Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed.Results: E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (P<0.05. A higher level of total cholesterol was associated with the E4 allele (adjusted odds ratio 1.689, 95% confidence interval 1.223–2.334, P<0.01. However, no association was found between APOE status and serum levels of glucose (adjusted odds ratio 0.981, 95% confidence interval 0.720–1.336, P=0.903 or total triglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759–1.429, P=0.800.Conclusion: A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides

  19. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

      Institute of Scientific and Technical Information of China (English)

      Xin Ma; Xun-Ming Ji; Paul Fu; Yu-Chuan Ding; Qiang Xue; Yue Huang

      2015-01-01

      Background:Cerebral venous thrombosis (CVT) may lead to serious neurological disorders;however,little is known about the risk factors for recurrent CVT.Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.Methods:This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital,Capital Medical University from August 2005 to September 2009.Demographic and clinical variables were collected,as well as laboratory parameters,including plasma fibrinogen and HDL-C.Patients with CVT were followed for recurrent symptomatic CVT.Follow-up was through the end of September 2010.Potential predictors of recurrence were analyzed using Cox survival analysis.Results:At the end of the follow-up,95 patients were eligible for the study.Twelve of 95 patients (12.6%) had recurred CVT.The median time of recurrence was 7 months (range:1-39 months).Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT.The recurrence rate of CVT was 2.76 per 100 patient-years.Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio:4.69;95% confidence interval:1.10-20.11;P < 0.05).Of the twelve patients with recurrent CVT in our study,7 (58.3%) had high fibrinogen plus low HDL-C levels.All 7 of these patients took warfarin for 3-12 months,and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.Conclusions:Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT.The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

  1. The Effects of Eight-Week Treatment with High Dose Vitamin E on Serum Cholesterol and Triglyceride Level of Patients with Schizophrenia on Olanzapine: A Placebo Controlled Study

    Directory of Open Access Journals (Sweden)

    Firoozeh Raisi

    2008-01-01

    Full Text Available "n  "n Objective: To study the effects of a high dose alpha-tocopherol on serum total cholesterol (TC, triglyceride (TG, and the high density lipoprotein (HDL levels of patients with schizophrenia receiving olanzapine. "nMethod: Thirty six adults diagnosed with schizophrenia based on DSM-IV who were taking olanzapine for a minimum of thirty days entered this eight-week, double blind, placebo-controlled study. Patients were randomized to receive alpha-tocopherol 400IU or placebo capsules twice a day for 2 weeks, then three times a day for 6 more weeks. Fasting total cholesterol (TC, triglyceride(TG,and HDL levels were measured at the baseline and weeks 4 and 8. "nResults: "nTC, TG and HDL levels did not change significantly during this study. There were no significant differences in TC, TG and HDL levels between the two groups at the baseline and weeks 4 and 8. "nConclusion: High-dose vitamin may not improve triglyceride and cholesterol levels in patients who are already on olanzapine. Further studies with greater number of patients and for a longer duration are needed.

  2. Uric Acid or 1-Methyl Uric Acid in the Urinary Bladder Increases Serum Glucose, Insulin, True Triglyceride, and Total Cholesterol Levels in Wistar Rats

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    T. Balasubramanian

    2003-01-01

    Full Text Available In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs, can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels.

  3. Impact of physiological levels of chenodeoxycholic acid supplementation on intestinal and hepatic bile acid and cholesterol metabolism in Cyp7a1-deficient mice.

    Science.gov (United States)

    Jones, Ryan D; Lopez, Adam M; Tong, Ernest Y; Posey, Kenneth S; Chuang, Jen-Chieh; Repa, Joyce J; Turley, Stephen D

    2015-01-01

    Mice deficient in cholesterol 7α-hydroxylase (Cyp7a1) have a diminished bile acid pool (BAP) and therefore represent a useful model for investigating the metabolic effects of restoring the pool with a specific BA. Previously we carried out such studies in Cyp7a1(-/-) mice fed physiological levels of cholic acid (CA) and achieved BAP restoration, along with an increased CA enrichment, at a dietary level of just 0.03% (w/w). Here we demonstrate that in Cyp7a1(-/-) mice fed chenodeoxycholic acid (CDCA) at a level of 0.06% (w/w), the BAP was restored to normal size and became substantially enriched with muricholic acid (MCA) (>70%), leaving the combined contribution of CA and CDCA to be Cyp7a1 deficiency such as an elevated rate of intestinal sterol synthesis, an enhanced level of mRNA for Cyp8b1 in the liver, and depressed mRNA levels for Ibabp, Shp and Fgf15 in the distal small intestine. When Cyp7a1(-/-) and matching Cyp7a1(+/+) mice were fed a diet with added cholesterol (0.2%) (w/w), either alone, or also containing CDCA (0.06%) (w/w) or CA (0.03%) (w/w) for 18days, the hepatic total cholesterol concentrations (mg/g) in the Cyp7a1(-/-) mice were 26.9±3.7, 16.4±0.9 and 47.6±1.9, respectively, vs. 4.9±0.4, 5.0±0.7 and 6.4±1.9, respectively in the corresponding Cyp7a1(+/+) controls. These data affirm the importance of using moderate levels of dietary BA supplementation to elicit changes in hepatic cholesterol metabolism through shifts in BAP size and composition.

  4. Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

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    Yan Ting-Ting

    2010-12-01

    Full Text Available Abstract Background The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1 gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, apolipoprotein (Apo AI and ApoB were lower in Bai Ku Yao than in Han (P P P P P P Conclusions These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.

  5. Prevalence and characteristics of patients with low levels of low-density lipoprotein cholesterol in northern Denmark: a descriptive study

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    Schmidt SA

    2015-02-01

    Full Text Available Sigrun Alba Johannesdottir Schmidt,1 Uffe Heide-Jørgensen,1 Angelika D Manthripragada,2 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Background: With the emergence of new lipid-lowering therapies, more patients are expected to achieve substantial lowering of low-density lipoprotein cholesterol (LDL-C. However, there are limited data examining the clinical experience of patients with low (<1.3 mmol/L or very low (<0.65 mmol/L levels of LDL-C. To provide information on patients with low LDL-C, we identified and characterized persons with low LDL-C using data from Danish medical databases. Methods: Using a population-based clinical laboratory database, we identified adults with at least one LDL-C measurement in northern Denmark between 1998 and 2011 (population approximately 1.5 million persons. Based on the lowest measurement during the study period, we divided patients into groups with low (<1.3 mmol/L, moderate (1.3–3.3 mmol/L, or high (>3.3 mmol/L LDL-C. We described their demographic characteristics, entire comorbidity history, and 90-day prescription history prior to the lowest LDL-C value measured. Finally, we further restricted the analysis to individuals with very low LDL-C (<0.65 mmol/L. Results: Among 765,503 persons with an LDL-C measurement, 23% had high LDL-C, 73% had moderate LDL-C, and 4.8% had low LDL-C. In the latter group, 9.6% (0.46% of total had very low LDL-C. Compared with the moderate and high LDL-C categories, the low LDL-C group included more males and older persons with a higher prevalence of cardiovascular disease, diabetes, chronic pulmonary disease, ulcer disease, and obesity, as measured by hospital diagnoses or relevant prescription drugs for these diseases. Cancer and use of psychotropic drugs were also more prevalent. These patterns of distribution became even more pronounced when

  6. Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans--a quantitative review.

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    Ingeborg A Brouwer

    Full Text Available BACKGROUND: Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA on blood lipoproteins, and compared these with industrial trans fatty acids. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95%CI 0.044-0.066 for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95%CI 0.012-0.065 for ruminant trans fatty acids, and 0.043 (95% CI 0.012-0.074 for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids. CONCLUSIONS/SIGNIFICANCE: Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol.

  7. Effect of plant extract of Tribulus terrestris and probiotics on the reproductive performance, total cholesterol and testosterone hormone levels of rams

    OpenAIRE

    2015-01-01

    The objective of this experiment was to compare between the effects of tribulus terrestris extract and probiotics on scrotal circumference, testicular volume, reaction time, semen characteristics, serum total cholesterol and testosterone hormone levels of rams. The study was carried out from February to July 2013 on eight sexually mature Rahmani rams. The eight rams were used as control group for one month before treatment (weekly assessment for all the parameters). Rams were divided into two...

  8. Formation of cholesterol bilayer domains precedes formation of cholesterol crystals in cholesterol/dimyristoylphosphatidylcholine membranes: EPR and DSC studies.

    Science.gov (United States)

    Mainali, Laxman; Raguz, Marija; Subczynski, Witold K

    2013-08-01

    Saturation-recovery EPR along with DSC were used to determine the cholesterol content at which pure cholesterol bilayer domains (CBDs) and cholesterol crystals begin to form in dimyristoylphosphatidylcholine (DMPC) membranes. To preserve compositional homogeneity throughout the membrane suspension, lipid multilamellar dispersions were prepared using a rapid solvent exchange method. The cholesterol content increased from 0 to 75 mol %. With spin-labeled cholesterol analogues, it was shown that the CBDs begin to form at ~50 mol % cholesterol. It was confirmed by DSC that the cholesterol solubility threshold for DMPC membranes is detected at ~66 mol % cholesterol. At levels above this cholesterol content, monohydrate cholesterol crystals start to form. The major finding is that the formation of CBDs precedes formation of cholesterol crystals. The region of the phase diagram for cholesterol contents between 50 and 66 mol % is described as a structured one-phase region in which CBDs have to be supported by the surrounding DMPC bilayer saturated with cholesterol. Thus, the phase boundary located at 66 mol % cholesterol separates the structured one-phase region (liquid-ordered phase of DMPC with CBDs) from the two-phase region where the structured liquid-ordered phase of DMPC coexists with cholesterol crystals. It is likely that CBDs are precursors of monohydrate cholesterol crystals.

  9. THE EFFECT OF ANTICONVULSANT DRUGS (PHENOBARBITAL AND VALPROIC ACID ON THE SERUM LEVEL OF CHOLESTEROL, TRIGLYCERIDE, LIPOPROTEIN AND LIVER ENZYMES IN CONVULSIVE CHILDREN

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    Mohammad Reza SALEHIOMRAN

    2010-12-01

    Full Text Available ObjectiveStudies on the effect of various antiepileptic drugs on serum lipids show contradictory results. We aimed to find the effect of Phenobarbital and Sodium Valproate monotherapy on serum lipid profile and liver function tests in epileptic children.Materials & MethodsThis cohort study was conducted in Amirkola Children Hospital. One hundred and ten children with epilepsy were included in this study. Children with hepatic or renal disease, those receiving medications which could alter liver function tests or serum lipid profile were excluded from the study. Patients were allocated into two groups. The first group, including 63 patients, received Phenobarbital and the second group, including 47 patients, received Sodium Valproate, both in divided doses. A venous blood sample was collected after overnight fasting to evaluate serum triglyceride, total cholesterol, LDL, HDL, and liver function tests. Data was analyzed with SPSS version 17.ResultsIn children receiving Phenobarbital, total cholesterol, LDL, HDL, ALP, SGOT and SGPT increased significantly after treatment, but TG level showed no significant changes. In children receiving Sodium Valproate, HDL, ALP, SGOT, SGPT significantly increased after treatment but there were no statistically significant changes in total cholesterol, LDL and TG. In our study, the plasma levels of LPa elevated significantly after treatment with Phenobarbital and Sodium Valproate (P Value=0.0001. This increase was more significant in patients receiving Sodium Valproate.ConclusionOur results suggested a need for monitoring serum total cholesterol, HDL, LDL, and TG levels in patients receiving Phenobarbital and Valproic Acid.Keywords: Seizure, Phenobarbital, Sodium Valproate.

  10. Effect of Different Levels of L-Carnitine on the Productive Performance, Egg Quality, Blood Parameters and Egg Yolk Cholesterol in Laying Hens

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    Kazemi-Fard M

    2015-12-01

    Full Text Available This experiment was conducted to investigate the effects of different levels of L-carnitine on productive performance, egg quality and blood parameters in laying hens. Forty-eight Hy-Line W-36 egg Layers were weighed at 90 weeks of age and randomly allocated into 16 cages (three hens per cage. Four dietary treatments were prepared by supplementing L-carnitine (0, 50, 100 and 150 mg/kg of diet to corn-soybean meal diet and offered ad libitum to hens. After two weeks of acclimatization, the eggs were weighed daily and feed intake as well as egg quality traits were measured biweekly. At the end of the experiment, two hens from each cage were selected to determine blood parameters and two eggs from each replicate were collected for cholesterol analysis. Results showed that L-carnitine supplementation at 100 and 150 mg/kg significantly increased egg production and egg mass, but decreased yolk cholesterol content. Laying hens receiving diet containing 50 mg/kg L-carnitine had significantly higher Hough unit, but lower progesterone than the hens fed control diet (P < 0.05. The results of this study showed that supplementing hens' diet with L-carnitine had beneficial effects on productive performance and decreased yolk cholesterol concentration; so it can be used as an effective supplement in the diet of laying hens.

  11. Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

    Science.gov (United States)

    Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

    2016-08-01

    Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

  12. Women and Cholesterol

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... 2014. Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  13. HDL Cholesterol Test

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    ... products and services. Advertising & Sponsorship: Policy | Opportunities HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  14. Cholesterol IQ Quiz

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    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  15. Cholesterol and Your Child

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cholesterol and Your Child KidsHealth > For Parents > Cholesterol and ... child's risk of developing heart disease later. About Cholesterol Cholesterol is a waxy substance produced by the ...

  16. Lifestyle Changes and Cholesterol

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    ... Venous Thromboembolism Aortic Aneurysm More Lifestyle Changes and Cholesterol Updated:Sep 26,2016 As part of a ... to the Terms and Conditions and Privacy Policy Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  17. Common Misconceptions about Cholesterol

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    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Apr 3,2017 Cholesterol can be both ... misconceptions about cholesterol. Click on each misconception about cholesterol to see the truth: My choices about diet ...

  18. LDL Cholesterol Test

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    ... products and services. Advertising & Sponsorship: Policy | Opportunities LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  19. Major Risk Factors for Heart Disease: High Blood Cholesterol

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    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  20. High Blood Cholesterol: What You Need to Know

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    ... Audiences Contact The Health Information Center High Blood Cholesterol: What You Need To Know Table of Contents ... Lifestyle Changes (TLC) Drug Treatment Resources Why Is Cholesterol Important? Your blood cholesterol level has a lot ...

  1. Alcohol Dehydrogenase-1B (rs1229984 and Aldehyde Dehydrogenase-2 (rs671 Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

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    Akira Yokoyama

    Full Text Available Elevated serum triglyceride (TG and high-density-lipoprotein cholesterol (HDL-C levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.The population consisted of 1806 Japanese alcoholic men (≥40 years who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.High serum levels of TG (≥150 mg/dl, HDL-C (>80 mg/dl, and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99-1.96], respectively, and decreased the OR for a high HDL-C level (0.37 [0.28-0.49] and 0.51 [0.37-0.69], respectively. The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]. The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl and HDL-C (≥100 mg/dl.The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL

  2. Knowledge-driven analysis identifies a gene-gene interaction affecting high-density lipoprotein cholesterol levels in multi-ethnic populations.

    Science.gov (United States)

    Ma, Li; Brautbar, Ariel; Boerwinkle, Eric; Sing, Charles F; Clark, Andrew G; Keinan, Alon

    2012-01-01

    Total cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels are among the most important risk factors for coronary artery disease. We tested for gene-gene interactions affecting the level of these four lipids based on prior knowledge of established genome-wide association study (GWAS) hits, protein-protein interactions, and pathway information. Using genotype data from 9,713 European Americans from the Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction between HMGCR and a locus near LIPC in their effect on HDL-C levels (Bonferroni corrected P(c) = 0.002). Using an adaptive locus-based validation procedure, we successfully validated this gene-gene interaction in the European American cohorts from the Framingham Heart Study (P(c) = 0.002) and the Multi-Ethnic Study of Atherosclerosis (MESA; P(c) = 0.006). The interaction between these two loci is also significant in the African American sample from ARIC (P(c) = 0.004) and in the Hispanic American sample from MESA (P(c) = 0.04). Both HMGCR and LIPC are involved in the metabolism of lipids, and genome-wide association studies have previously identified LIPC as associated with levels of HDL-C. However, the effect on HDL-C of the novel gene-gene interaction reported here is twice as pronounced as that predicted by the sum of the marginal effects of the two loci. In conclusion, based on a knowledge-driven analysis of epistasis, together with a new locus-based validation method, we successfully identified and validated an interaction affecting a complex trait in multi-ethnic populations.

  3. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    Science.gov (United States)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Ángeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Cátira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 × 10−11) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations. PMID:20418488

  4. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  5. SPARCL: a high-altitude tethered balloon-based optical space-to-ground communication system

    Science.gov (United States)

    Badesha, Surjit S.

    2002-12-01

    The Johns Hopkins University Applied Physics Laboratory (JHU/APL) has conducted a feasibility study to determine if a high altitude (20 km) tethered balloon-based space-to-ground optical communication system is a feasible concept. To support this effort, a detailed concept definition was developed and associated issues were identified and analyzed systematically. Of all the adverse atmospheric phenomena, cloud coverage was identified as the most prohibitive obstacle for a space-to-ground optical communication link. However, by placing a receiver on a balloon at a 20 km altitude, the proposed high altitude system avoids virtually all atmospheric effects. A practical notional scenario was developed (i.e. surveillance and/or reconnaissance of a regional conflict) involving end-to-end optical communication architecture to identify system elements, system level requirements, and to quantify realistic data rate requirements. Analysis of the proposed space-to-ground communication elements indicates that while significant development is required, the system is technically feasible and is a very cost effective 24/7solution.

  6. Dietary levels of chia: influence on yolk cholesterol, lipid content and fatty acid composition for two strains of hens.

    Science.gov (United States)

    Ayerza, R; Coates, W

    2000-05-01

    Four hundred fifty H&N laying hens, half white and half brown, were fed for 90 d to compare a control diet to diets containing 7, 14, 21, and 28% chia (Salvia hispanica L.) seed. Cholesterol content, total fat content, and fatty acid composition of the yolks were determined 30, 43, 58, 72, and 90 d from the start of the trial. Significantly less cholesterol was found in the egg yolks produced by the hens fed the diets with 14, 21, and 28% chia compared with the control, except at Day 90. Palmitic fatty acid content and total saturated fatty acid content decreased as chia percentage increased and as the trial progressed. Total omega-3 fatty acid content was significantly greater (P < 0.05) for both strains for all chia diets compared with the control diet. Total polyunsaturated fatty acid (PUFA) content of the yolks from the chia diets was significantly greater (P < 0.05) than from the control diet. Generally, total PUFA content tended to be highest in the yolks of the white hens.

  7. Phenotypic factors influencing the variation in response of circulating cholesterol level to personalised dietary advice in the Food4Me study.

    Science.gov (United States)

    Kirwan, Laura; Walsh, Marianne C; Celis-Morales, Carlos; Marsaux, Cyril F M; Livingstone, Katherine M; Navas-Carretero, Santiago; Fallaize, Rosalind; O'Donovan, Clare B; Woolhead, Clara; Forster, Hannah; Kolossa, Silvia; Daniel, Hannelore; Moschonis, George; Manios, Yannis; Surwillo, Agnieszka; Godlewska, Magdalena; Traczyk, Iwona; Drevon, Christian A; Gibney, Mike J; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim H M; Mathers, John C; Gibney, Eileen R; Brennan, Lorraine

    2016-12-01

    Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.

  8. The Effect of Hydroalcoholic Extract of Glycyrrhizaglabra L. (licorice Root on Serum Level of Glucose, Triglyceride and Cholesterol in Polycystic Ovary Syndrome Induced by Letrozole in Rats

    Directory of Open Access Journals (Sweden)

    F Barazesh

    2016-05-01

    Full Text Available Background & aim: Polycystic ovary syndrome (PCOS is the most common endocrine disorder which effects 15.6 %  of women in Iran. Licorice (Glycyrrhizaglabra L. has phytoestrogenic and anti-diabetic effects. The aim of this study was to investigate the effects of hydro-alcoholic Licorice root extract on blood sugar, triglycerides and cholesterol in the rats with PCOS. Methods: In the present experimental study, 50 female puber Sprague dawley (180±20 gr rats with regular sexual cycle were entered in the study.  Studied groups included: first, the Normal group, receiving carrier (normal saline (2 ml/kg daily orally for 21 days. Then, the letrozole group which received letrozole (1 mg/kg dissolved in normal saline (2 ml/kg for 21 days and then normal saline (2 ml/kg daily orally for 30 days. The last groups, Treatment groups 1 and 2, which received letrozole (1 mg/kg dissolved in normal saline (2 ml/kg for 21 days then hydroalcoholic extract of Licorice root (200 and 400 mg/kg dissolved in normal saline (2 ml/kg daily, orally for 30 days respectively. To conclude, blood samples were collected from the heart and also the serum level of blood sugar, triglyceride and cholesterol was measured. The data were analyzed using one-way ANOVA (p< 0.05. Results: The mean serum level of blood sugar increased in the Letrozole group compared to the normal group and decreased in the treatment groups compared to Letrozole group (p< 0.05. No statistically significant differences were seen in mean of serum level of triglyceride and cholesterol between all groups. Conclusion: The licoricecan extract improved the adverse side-effects caused by diabetese in polycystic ovary syndrome However, its effect on dyslipidemia in patients requiring further investigations.

  9. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  10. Public health aspects of serum cholesterol

    NARCIS (Netherlands)

    S. Houterman (Saskia)

    2001-01-01

    textabstractIn the beginning of this century Anitschkow and De Langen started pioneering work concerning the relation between cholesterol and coronary heart disease. Both showed that there was a possible relation between cholesterol in the diet, blood cholesterol levels and atherosclerosis. It took

  11. The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population

    NARCIS (Netherlands)

    Lu, Y.; Feskens, E.J.M.; Boer, J.M.A.; Müller, M.R.

    2010-01-01

    The liver is currently known to be the major organ to eliminate excess cholesterol from our body. It accomplishes this function in two ways: conversion of cholesterol molecules into bile acids (BAs) and secretion of unesterified cholesterol molecules into bile. BAs are synthesized in the hepatocytes

  12. Contribution of education level and dairy fat sources to serum cholesterol in Russian and Finnish Karelia: results from four cross-sectional risk factor surveys in 1992–2007

    Directory of Open Access Journals (Sweden)

    Paalanen Laura

    2012-10-01

    Full Text Available Abstract Background Food habits vary by socio-economic group and geographic area. Data on socio-economic differences in food habits and in serum total cholesterol concentration from Russia are scarce. Our aim was to examine changes and educational differences in serum total cholesterol and in the consumption of major sources of saturated fat in two geographically neighbouring areas, Russian and Finnish Karelia, and to examine whether the foods associated with serum total cholesterol are different in the two areas. Methods Data from cross-sectional risk factor surveys from years 1992, 1997, 2002 and 2007 in the district of Pitkäranta, the Republic of Karelia, Russia (n = 2672, and North Karelia, Finland (n = 5437, were used. The analyses included two phases. 1 To examine the differences in cholesterol by education, the means and 95% confidence intervals for education groups were calculated for each study year. 2 Multivariate linear regression analysis was employed to examine the role of butter in cooking, butter on bread, fat-containing milk and cheese in explaining serum total cholesterol. In these analyses, the data for all four study years were combined. Results In Pitkäranta, serum total cholesterol fluctuated during the study period (1992–2007, whereas in North Karelia cholesterol levels declined consistently. No apparent differences in cholesterol levels by education were observed in Pitkäranta. In North Karelia, cholesterol was lower among subjects in the highest education tertile compared to the lowest education tertile in 1992 and 2002. In Pitkäranta, consumption of fat-containing milk was most strongly associated with cholesterol (β=0.19, 95% CI 0.10, 0.28 adjusted for sex, age, education and study year. In North Karelia, using butter in cooking (β=0.09, 95% CI 0.04, 0.15 and using butter on bread (β=0.09, 95% CI 0.02, 0.15 had a significant positive association with cholesterol. Conclusions In the two geographically

  13. What Is Cholesterol?

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol Print A A A ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  14. What Is Cholesterol?

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol A A A What's ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  15. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet

    2011-01-01

    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  16. Cholesterol Worships a New Idol

    Institute of Scientific and Technical Information of China (English)

    Ira G. Schulman

    2009-01-01

    The growing worldwide epidemic of cardiovascular disease suggests that new therapeutic strategies are needed to complement statins in the lowering of cholesterol levels. In a recent paper in Science, Tontonoz and colleagues have identified Idol as a protein that can control cholesterol levels by regulating the stability of the low-density lipoprotein receptor; inhibiting the activity of Idol could provide novel approaches for the treatment of cardiovascular disease.

  17. Cholesterol metabolism and colon cancer.

    Science.gov (United States)

    Broitman, S A; Cerda, S; Wilkinson, J

    1993-01-01

    While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use

  18. A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

    Science.gov (United States)

    Hirata, Takumi; Sugiyama, Daisuke; Nagasawa, Shin-Ya; Murakami, Yoshitaka; Saitoh, Shigeyuki; Okayama, Akira; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Miyamoto, Yoshihiro; Yamada, Michiko; Ishikawa, Shizukiyo; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

    2016-10-05

    Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

  19. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Blood Pressure Salt Million Hearts® WISEWOMAN Program High Cholesterol Facts Recommend on Facebook Tweet Share Compartir As ... the facts about high cholesterol [PDF-281K] . High Cholesterol in the United States 73.5 million adults ( ...

  20. Get Your Cholesterol Checked

    Science.gov (United States)

    ... Checked Print This Topic En español Get Your Cholesterol Checked Browse Sections The Basics Overview Cholesterol Test ... How often do I need to get my cholesterol checked? The general recommendation is to get your ...

  1. Dietary Fat and Cholesterol

    Science.gov (United States)

    ... Conditions Nutrition & Fitness Emotional Health Dietary Fat and Cholesterol Posted under Health Guides . Updated 7 March 2017. + ... saturated fat found in red meat. What is cholesterol? Cholesterol is a fatlike substance that’s found in ...

  2. High Blood Cholesterol Prevention

    Science.gov (United States)

    ... Million Hearts® WISEWOMAN Program Prevention and Management of High LDL Cholesterol: What You Can Do Recommend on ... like eating a healthy diet, can help prevent high cholesterol. High low-density lipoprotein (LDL) cholesterol increases ...

  3. Cholesterol lowering, low cholesterol, and mortality.

    Science.gov (United States)

    LaRosa, J C

    1993-10-01

    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  4. Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed whey and lactose-hydrolysed condensed whey on serum cholesterol and triacylglycerol levels in rats.

    Science.gov (United States)

    Beena, A; Prasad, V

    1997-08-01

    The possible hypocholesterolaemic properties of milk and fermented milk products have been investigated in groups of albino rats given a basal diet, basal diet plus cholesterol, and basal diet plus cholesterol together with whole milk or standard or bifidus yogurt. The yogurts were fortified with skim milk powder, condensed whey or lactose-hydrolysed condensed whey. After 30 d, triacylglycerols, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured in serum. Whole milk and ordinary yogurt had no hypocholesterolaemic effect, but standard yogurt containing lactose-hydrolysed condensed whey and all bifidus yogurts lowered serum cholesterol. In general, yogurts changed HDL-cholesterol little, but tended to raise triacylglycerols. There was marked lowering of LDL-cholesterol in rats given either type of yogurt fortified with whey proteins. This study has demonstrated in a rat model that bifidus yogurts and yogurts fortified with whey proteins can reduce total and LDL-cholesterol, and suggests that if they have the same effect in human subjects they have potential value in cholesterol-lowering diets.

  5. Cholesterol testing on a smartphone.

    Science.gov (United States)

    Oncescu, Vlad; Mancuso, Matthew; Erickson, David

    2014-02-21

    Home self-diagnostic tools for blood cholesterol monitoring have been around for over a decade but their widespread adoption has been limited by the relatively high cost of acquiring a quantitative test-strip reader, complicated procedure for operating the device, and inability to easily store and process results. To address this we have developed a smartphone accessory and software application that allows for the quantification of cholesterol levels in blood. Through a series of human trials we demonstrate that the system can accurately quantify total cholesterol levels in blood within 60 s by imaging standard test strips. In addition, we demonstrate how our accessory is optimized to improve measurement sensitivity and reproducibility across different individual smartphones. With the widespread adoption of smartphones and increasingly sophisticated image processing technology, accessories such as the one presented here will allow cholesterol monitoring to become more accurate and widespread, greatly improving preventive care for cardiovascular disease.

  6. Mechanism of Resistance to Dietary Cholesterol

    Directory of Open Access Journals (Sweden)

    Lindsey R. Boone

    2011-01-01

    Full Text Available Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1. These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1 protein levels, which were not increased in response to diets containing 2% cholesterol.

  7. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.

    Science.gov (United States)

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang

    2016-03-01

    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  8. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  9. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan Albert; Tietge, Uwe J.F.; Brufau Dones, Gemma; Groen, Albert K

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins we

  10. Knowledge-driven multi-locus analysis reveals gene-gene interactions influencing HDL cholesterol level in two independent EMR-linked biobanks.

    Science.gov (United States)

    Turner, Stephen D; Berg, Richard L; Linneman, James G; Peissig, Peggy L; Crawford, Dana C; Denny, Joshua C; Roden, Dan M; McCarty, Catherine A; Ritchie, Marylyn D; Wilke, Russell A

    2011-05-11

    Genome-wide association studies (GWAS) are routinely being used to examine the genetic contribution to complex human traits, such as high-density lipoprotein cholesterol (HDL-C). Although HDL-C levels are highly heritable (h(2)∼0.7), the genetic determinants identified through GWAS contribute to a small fraction of the variance in this trait. Reasons for this discrepancy may include rare variants, structural variants, gene-environment (GxE) interactions, and gene-gene (GxG) interactions. Clinical practice-based biobanks now allow investigators to address these challenges by conducting GWAS in the context of comprehensive electronic medical records (EMRs). Here we apply an EMR-based phenotyping approach, within the context of routine care, to replicate several known associations between HDL-C and previously characterized genetic variants: CETP (rs3764261, p = 1.22e-25), LIPC (rs11855284, p = 3.92e-14), LPL (rs12678919, p = 1.99e-7), and the APOA1/C3/A4/A5 locus (rs964184, p = 1.06e-5), all adjusted for age, gender, body mass index (BMI), and smoking status. By using a novel approach which censors data based on relevant co-morbidities and lipid modifying medications to construct a more rigorous HDL-C phenotype, we identified an association between HDL-C and TRIB1, a gene which previously resisted identification in studies with larger sample sizes. Through the application of additional analytical strategies incorporating biological knowledge, we further identified 11 significant GxG interaction models in our discovery cohort, 8 of which show evidence of replication in a second biobank cohort. The strongest predictive model included a pairwise interaction between LPL (which modulates the incorporation of triglyceride into HDL) and ABCA1 (which modulates the incorporation of free cholesterol into HDL). These results demonstrate that gene-gene interactions modulate complex human traits, including HDL cholesterol.

  11. Cooking for Lower Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Cooking for Lower Cholesterol Updated:Oct 28,2016 A heart-healthy eating ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  12. Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Xin Ma

    2015-01-01

    Conclusions: Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

  13. Effects of Past and Recent Blood Pressure and Cholesterol Level on Coronary Heart Disease and Stroke Mortality, Accounting for Measurement Error

    NARCIS (Netherlands)

    Boshuizen, H.C.; Lanti, M.; Menotti, A.; Moschandreas, J.; Tolonen, H.; Nissinen, A.; Nedeljkovic, S.; Kafatos, A.; Kromhout, D.

    2007-01-01

    The authors aimed to quantify the effects of current systolic blood pressure (SBP) and serum total cholesterol on the risk of mortality in comparison with SBP or serum cholesterol 25 years previously, taking measurement error into account. The authors reanalyzed 35-year follow-up data on mortality d

  14. Effects of Past and Recent Blood Pressure and Cholesterol Level on Coronary Heart Disease and Stroke Mortality, Accounting for Measurement Error - Reply ( letter to the editor

    NARCIS (Netherlands)

    Boshuizen, H.C.; Lanti, M.; Menotti, A.; Moschandreas, J.; Tolonen, H.; Nissinen, A.; Nedeljkovic, S.; Kafatos, A.; Kromhout, D.

    2008-01-01

    The authors aimed to quantify the effects of current systolic blood pressure (SBP) and serum total cholesterol on the risk of mortality in comparison with SBP or serum cholesterol 25 years previously, taking measurement error into account. The authors reanalyzed 35-year follow-up data on mortality d

  15. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  16. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  17. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

    Science.gov (United States)

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

    2013-04-01

    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  18. Evaluating computational models of cholesterol metabolism.

    Science.gov (United States)

    Paalvast, Yared; Kuivenhoven, Jan Albert; Groen, Albert K

    2015-10-01

    Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of cholesterol synthesis and plasma cholesterol levels is incomplete. One way of addressing the remaining questions is by making use of computational models. Here, we critically evaluate existing computational models of cholesterol metabolism making use of ordinary differential equations and addressed whether they used assumptions and make predictions in line with current knowledge on cholesterol homeostasis. Having studied the results described by the authors, we have also tested their models. This was done primarily by testing the effect of statin treatment in each model. Ten out of eleven models tested have made assumptions in line with current knowledge of cholesterol metabolism. Three out of the ten remaining models made correct predictions, i.e. predicting a decrease in plasma total and LDL cholesterol or increased uptake of LDL upon treatment upon the use of statins. In conclusion, few models on cholesterol metabolism are able to pass a functional test. Apparently most models have not undergone the critical iterative systems biology cycle of validation. We expect modeling of cholesterol metabolism to go through many more model topologies and iterative cycles and welcome the increased understanding of cholesterol metabolism these are likely to bring.

  19. Serum apolipoprotein(a) levels and its effect on the measured values of low density lipoprotein cholesterol.

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Serum low density lipoprotein cholesterl (LDL-C) and lipoprotein(a)[Lp(a)]levels were analyzed in 1032 sequential cases on routine physical check up, with special attention to the effect of Lp(a) on the LDL-C values. Since the determination of LDL-C by various

  20. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    NARCIS (Netherlands)

    van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W. J. H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J. M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Cupples, L. Adrienne; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I. W.; Slagboom, P. Eline; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (similar to 35,000 samples) with the population-specific reference pan

  1. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    NARCIS (Netherlands)

    Van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; Van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; Van Dijk, Freerk; Willemsen, Gonneke; De Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W J H; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; De Craen, Anton J M; Uh, Hae Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Cupples, L. Adrienne; Jukema, J. Wouter; Van Der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke Jan; Uitterlinden, Andre G.; Swertz, Morris A.; Van Ommen, Gert Jan B; De Bakker, Paul I W; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; Van Duijn, Cornelia M.; Neerincx, Pieter B T; Elbers, Clara C.; Palamara, Pier Francesco; Peer, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; Van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F J; Stoneking, Mark; De Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; Van Den Berg, Leonard H.; Byelas, Heorhiy; Den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Van Der Velde, K. Joeri; Van Setten, Jessica; Kattenberg, Mathijs; Van Schaik, Barbera D C; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; de Bakker, Paul I W

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created

  2. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    NARCIS (Netherlands)

    E.M. van Leeuwen (Elisa); L.C. Karssen (Lennart); J. Deelen (Joris); A. Isaacs (Aaron); M.C. Medina-Gomez (Carolina); H. Mbarek; A. Kanterakis (Alexandros); S. Trompet (Stella); D. Postmus (Douwe); N. Verweij (Niek); D. van Enckevort (David); J.E. Huffman (Jennifer); C.C. White (Charles); M.F. Feitosa (Mary Furlan); T.M. Bartz (Traci M.); A. Manichaikul (Ani); P.K. Joshi (Peter); G.M. Peloso (Gina); P. Deelen (Patrick); F. van Dijk (F.); G.A.H.M. Willemsen (Gonneke); E.J.C. de Geus (Eco); Y. Milaneschi (Yuri); B.W.J.H. Penninx (Brenda); L.C. Francioli (Laurent); A. Menelaou (Androniki); S.L. Pulit (Sara); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); B.A. Oostra (Ben); O.H. Franco (Oscar); I.M. Leach (Irene Mateo); M. Beekman (Marian); A.J. de Craen (Anton); H.-W. Uh (Hae-Won); H. Trochet (Holly); L.J. Hocking (Lynne); D.J. Porteous (David J.); N. Sattar (Naveed); C.J. Packard (Chris J.); B.M. Buckley (Brendan M.); J. Brody (Jennifer); J.C. Bis (Joshua); J.I. Rotter (Jerome I.); J.C. Mychaleckyj (Josyf); H. Campbell (Harry); Q. Duan (Qing); L.A. Lange (Leslie); J.F. Wilson (James F); C. Hayward (Caroline); O. Polasek (Ozren); V. Vitart (Veronique); I. Rudan (Igor); A. Wright (Alan); S.S. Rich (Stephen S.); B.M. Psaty (Bruce); I.B. Borecki (Ingrid); P.M. Kearney (Patricia M.); D.J. Stott (David. J.); L.A. Cupples (Adrienne); J.W. Jukema (Jan Wouter); P. van der Harst (Pim); E.J.G. Sijbrands (Eric); J.J. Hottenga (Jouke Jan); A.G. Uitterlinden (André); M. Swertz (Morris); G.-J.B. Van Ommen (Gert-Jan B.); P.I.W. de Bakker (Paul); P. Eline Slagboom; D.I. Boomsma (Dorret); C. Wijmenga (Cisca); C.M. van Duijn (Cock); P.B.T. Neerincx (Pieter B T); C.C. Elbers (Clara); P.F. Palamara (Pier Francesco); I. Peer (Itsik); M. Abdellaoui (Mohammed); W.P. Kloosterman (Wigard); M. van Oven (Mannis); M. Vermaat (Martijn); M. Li (Mingkun); J.F.J. Laros (Jeroen F.); M. Stoneking (Mark); P. de Knijff (Peter); M.H. Kayser (Manfred); J.H. Veldink (Jan); L.H. van den Berg (Leonard); H. Byelas (Heorhiy); J.T. den Dunnen (Johan); M.K. Dijkstra; N. Amin (Najaf); K.J. Van Der Velde (K. Joeri); J. van Setten (Jessica); V.M. Kattenberg (Mathijs); F.D.M. Van Schaik (Fiona D.M.); J.J. Bot (Jan); I.J. Nijman (Isaac ); H. Mei (Hailiang); V. Koval (Vyacheslav); K. Ye (Kai); E.-W. Lameijer (Eric-Wubbo); H. Moed (Heleen); J. Hehir-Kwa (Jayne); R.E. Handsaker (Robert); S.R. Sunyaev (Shamil); M. Sohail (Mashaal); F. Hormozdiari (Fereydoun); T. Marschall (Tanja); A. Schönhuth (Alexander); V. Guryev (Victor); H.E.D. Suchiman (Eka); B.H.R. Wolffenbuttel (Bruce); I. Platteel (Inge); S.J. Pitts (Steven); S. Potluri (Shobha); D.R. Cox (David R.); Q. Li (Qibin); Y. Li (Yingrui); Y. Du (Yuanping); R. Chen (Ruoyan); H. Cao (Hongzhi); N. Li (Ning); S. Cao (Sujie); J. Wang (Jun); J.A. Bovenberg (Jasper)

    2015-01-01

    textabstractVariants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference p

  3. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  4. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  5. Cis-9, trans-11 and trans-10, cis-12 CLA mixture does not change body composition, induces insulin resistance and increases serum HDL cholesterol level in rats.

    Science.gov (United States)

    de Almeida, Mariana Macedo; de Souza, Yamara Oliveira; Dutra Luquetti, Sheila Cristina Potente; Sabarense, Céphora Maria; do Amaral Corrêa, José Otávio; da Conceição, Ellen Paula Santos; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; Andrade Soares, Sara Malaguti; Moura Gualberto, Ana Cristina; Gameiro, Jacy; da Gama, Marco Antônio Sundfeld; Ferraz Lopes, Fernando César; González Garcia, Raúl Marcel

    2015-01-01

    Synthetic supplements of conjugated linoleic acid (CLA) containing 50:50 mixture of cis-9, trans-11 and trans-10, cis-12 CLA isomers have been commercialized in some places for reducing body fat. However the safety of this CLA mixture is controversial and in some countries the CLA usage as food supplement is not authorized. Changes in insulinemic control and serum lipids profile are potential negative effects related to consumption of CLA mixture. The present study aimed to evaluate the effects of a diet containing mixture of cis-9, trans-11 and trans-10, cis-12 CLA on prevention of obesity risk as well as on potential side effects such as insulin resistance and dyslipidemia in Wistar rats. Thirty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: Normolipidic Control (NC), diet containing 4.0% soybean oil (SO); High Fat-Control (HF-C), diet containing 24.0% SO; High Fat-synthetic CLA (HF-CLA), diet containing 1.5% of an isomeric CLA mixture (Luta-CLA 60) and 22.5% SO. Luta-CLA 60 (BASF) contained nearly 60% of CLA (cis-9, trans-11 and trans-10, cis-12 CLA at 50:50 ratio). The HF-CLA diet contained 0.3% of each CLA isomer. HF-CLA diet had no effect on dietary intake and body composition. HF-CLA-fed rats had lower levels of PPARγ protein in retroperitoneal adipose tissue, hyperinsulinemia compared to HF-C-fed rats, hyperglycemia compared to NC-fed rats while no differences in glycemia were observed between NC and HF-C groups, increased HOMA index and higher levels of serum HDL cholesterol. Thus, feeding rats with a high fat diet containing equal parts of cis-9, trans-11 and trans-10, cis-12 CLA isomers had no effect on body composition and induced insulin resistance. Despite HF-CLA-fed rats had increased serum HDL cholesterol levels, caution should be taken before synthetic supplements containing cis-9, trans-11 and trans-10, cis-12 CLA are recommended as a nutritional strategy for weight management.

  6. Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women.

    Science.gov (United States)

    Taghizadeh, Mohsen; Hashemi, Teibeh; Shakeri, Hossein; Abedi, Fatemeh; Sabihi, Sima-Sadat; Alizadeh, Sabihe-Alsadat; Asemi, Zatolla

    2014-02-01

    To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10⁷ CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P > 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3.

  7. Carnosic acid-rich rosemary (Rosmarinus officinalis L.) leaf extract limits weight gain and improves cholesterol levels and glycaemia in mice on a high-fat diet.

    Science.gov (United States)

    Ibarra, Alvin; Cases, Julien; Roller, Marc; Chiralt-Boix, Amparo; Coussaert, Aurélie; Ripoll, Christophe

    2011-10-01

    Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemic effects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventive effects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain, glucose levels and lipid homeostasis in mice that had begun a high-fat diet (HFD) as juveniles. The animals were given a low-fat diet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasma cholesterol levels. In addition, we evaluated the inhibitory effects of RE in vitro on pancreatic lipase and PPAR-γ agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.

  8. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  9. Non-High-Density Lipoprotein Cholesterol Levels on the Risk of Asymptomatic Intracranial Arterial Stenosis: A Result from the APAC Study

    Science.gov (United States)

    Wu, Jianwei; Wang, Anxin; Li, Xin; Wu, Shouling; Zhao, Xingquan

    2016-01-01

    Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack (TIA), and the correlation between the plasma non-high density cholesterol (non-HDLC) levels and ICAS, especially asymptomatic ICAS (AICAS) is not clear. The Asymptomatic Polyvascular Abnormalities Community(APAC) study is a community-based, prospective, long-term follow-up observational study. 3387 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 3 groups based on their non-HDLC levels. The cox regression was used to analyze the correlation between the non-HDLC level and the incidence of AICAS.9.98% of the participants were diagnosed with AICAS during 2 years following up. Multivariate analysis showed that non-HDL-C is an independent indicator for the incidence of AICAS (HR = 1.22, 95%CI: 1.06–1.40), The incidence of AICAS gradually increase with the increasing non-HDLC level. Compared with subgroup(non-HDLC < 3.4 mmol/l), incidence of AICAS was significantly higher in the subgroups(non-HDLC 3.4–4.1 mmol/l and non-HDLC ≥ 4.1 mmol/l) after adjustment for the confounding factors (HR = 1.32, 95%CI:1.02–1.73; HR = 1.46, 95%CI: 1.10–1.94, respectively). In conclusions, our findings suggest that elevated non-HDLC levels a significant risk factor for the development of AICAS in the APAC study. PMID:27857223

  10. Identification of Sequence Variation in the Apolipoprotein A2 Gene and Their Relationship with Serum High-Density Lipoprotein Cholesterol Levels

    Science.gov (United States)

    Bandarian, Fatemeh; Daneshpour, Maryam Sadat; Hedayati, Mehdi; Naseri, Mohsen; Azizi, Fereidoun

    2016-01-01

    Background: Apolipoprotein A2 (APOA2) is the second major apolipoprotein of the high-density lipoprotein cholesterol (HDL-C). The study aim was to identify APOA2 gene variation in individuals within two extreme tails of HDL-C levels and its relationship with HDL-C level. Methods: This cross-sectional survey was conducted on participants from Tehran Glucose and Lipid Study (TLGS) at Research Institute for Endocrine Sciences, Tehran, Iran from April 2012 to February 2013. In total, 79 individuals with extreme low HDL-C levels (≤5th percentile for age and gender) and 63 individuals with extreme high HDL-C levels (≥95th percentile for age and gender) were selected. Variants were identified using DNA amplification and direct sequencing. Results: Screen of all exons and the core promoter region of APOA2 gene identified nine single nucleotide substitutions and one microsatellite; five of which were known and four were new variants. Of these nine variants, two were common tag single nucleotide polymorphisms (SNPs) and seven were rare SNPs. Both exonic substitutions were missense mutations and caused an amino acid change. There was a significant association between the new missense mutation (variant Chr.1:16119226, Ala98Pro) and HDL-C level. Conclusion: None of two common tag SNPs of rs6413453 and rs5082 contributes to the HDL-C trait in Iranian population, but a new missense mutation in APOA2 in our population has a significant association with HDL-C. PMID:26590203

  11. Cholesterol and late-life cognitive decline.

    Science.gov (United States)

    van Vliet, Peter

    2012-01-01

    High cholesterol levels are a major risk factor for cardiovascular disease, but their role in dementia and cognitive decline is less clear. This review highlights current knowledge on the role of cholesterol in late-life cognitive function, cognitive decline, and dementia. When measured in midlife, high cholesterol levels associate with an increased risk of late-life dementia and cognitive decline. However, when measured in late-life, high cholesterol levels show no association with cognitive function, or even show an inverse relation. Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function. Lowering cholesterol levels may impair brain function, since cholesterol is essential for synapse formation and maturation and plays an important role in the regulation of signal transduction through its function as a component of the cell membrane. However, membrane cholesterol also plays a role in the formation and aggregation of amyloid-β. Factors that influence cholesterol metabolism, such as dietary intake, are shown to play a role in late-life cognitive function and the risk of dementia. In conclusion, cholesterol associates with late-life cognitive function, but the association is strongly age-dependent. There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function.

  12. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment : individual patient meta-analysis of 13,677 subjects

    NARCIS (Netherlands)

    Boekholdt, S M; Sacks, F M; Jukema, J W; Shepherd, J; Freeman, D J; McMahon, A D; Cambien, F; Nicaud, V; de Grooth, G J; Talmud, P J; Humphries, S E; Miller, G J; Eiriksdottir, G; Gudnason, V; Kauma, H; Kakko, S; Savolainen, M J; Arca, M; Montali, A; Liu, S; Lanz, H J; Zwinderman, A H; Kuivenhoven, J A; Kastelein, J J P

    2005-01-01

    BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated betw

  13. Rosuvastatin for Primary Prevention in Older Persons With Elevated C-Reactive Protein and Low to Average Low-Density Lipoprotein Cholesterol Levels: Exploratory Analysis of a Randomized Trial

    DEFF Research Database (Denmark)

    Glynn, R.J.; Koenig, W.; Nordestgaard, B.G.;

    2010-01-01

    Background: Randomized data on statins for primary prevention in older persons are limited, and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age. Objective: To assess the efficacy and safety of rosuvastatin in persons 70 years ...

  14. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  15. In vivo exposure of young adult male rats to methoxychlor reduces serum testosterone levels and ex vivo Leydig cell testosterone formation and cholesterol side-chain cleavage activity.

    Science.gov (United States)

    Murono, Eisuke P; Derk, Raymond C; Akgul, Yucel

    2006-02-01

    Methoxychlor (MC) was developed as a replacement for the banned pesticide DDT. After in vivo administration, it is metabolized in the liver to 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), which is proposed to be the active agent. Both MC and HPTE have been shown to exhibit weak estrogenic and antiandrogenic activities, and they are thought to exert their effects through estrogen and androgen receptors, respectively. Although in vitro studies using cultured rat Leydig cells have reported that HPTE inhibits both basal and hCG-stimulated testosterone formation, the response of circulating testosterone levels to in vivo MC has been more variable. Therefore, the current studies evaluated whether the daily in vivo administration of MC (0, 5, 40 and 200 mg/kg body weight) for a short duration (days 54-60 of age) by gavage altered serum testosterone levels and ex vivo Leydig cell testosterone formation in young adult male rats. These results demonstrate that both fluid-retained and fluid-expressed seminal vesicle weights declined to 44 and 60% of control, respectively, in the 200 mg/kg MC-exposed animals. Similarly, serum testosterone and dehydroepiandrosterone levels declined to 41 and 45% of control, respectively, in the 200 mg/kg MC-exposed animals; however, serum LH and FSH levels were unaffected. Ex vivo Leydig cell basal testosterone formation over 4h declined to 49% of control in animals exposed to 200 mg/kg MC, and ex vivo Leydig cell P450 cholesterol side-chain cleavage activity declined to 79 and 50% of control in animals exposed to 40 and 200 mg/kg of MC, respectively, supporting previous in vitro studies which demonstrated the sensitivity of this step to MC.

  16. Study protocol: SPARCLE – a multi-centre European study of the relationship of environment to participation and quality of life in children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Colver Allan

    2006-04-01

    Full Text Available Abstract Background SPARCLE is a nine-centre European epidemiological research study examining the relationship of participation and quality of life to impairment and environment (physical, social and attitudinal in 8–12 year old children with cerebral palsy. Concepts are adopted from the International Classification of Functioning, Disability and Health which bridges the medical and social models of disability. Methods/Design A cross sectional study of children with cerebral palsy sampled from total population databases in 9 European regions. Children were visited by research associates in each country who had been trained together. The main instruments used were KIDSCREEN, Life-H, Strength and Difficulties Questionnaire, Parenting Stress Index. A measure of environment was developed within the study. All instruments were translated according to international guidelines. The potential for bias due to non response and missing data will be examined. After initial analysis using multivariate regression of how the data captured by each instrument relate to impairment and socio-economic characteristics, relationships between the latent traits captured by the instruments will then be analysed using structural equation modelling. Discussion This study is original in its methods by directly engaging children themselves, ensuring those with learning or communication difficulty are not excluded, and by studying in quantitative terms the crucial outcomes of participation and quality of life. Specification and publication of this protocol prior to analysis, which is not common in epidemiology but well established for randomised controlled trials and systematic reviews, should avoid the pitfalls of data dredging and post hoc analyses.

  17. Cholesterol levels in panic disorder, generalized anxiety disorder and major depression Níveis de colesterol no transtorno de pânico, transtorno de ansiedade generalizada e depressão maior

    Directory of Open Access Journals (Sweden)

    ACIOLY L.T. LACERDA

    2000-06-01

    Full Text Available Serum plasma total cholesterol levels were measured in 85 male or female outpatients with panic disorder (PD; N=41, generalized anxiety disorder (GAD; N=23 and major depression (MD; N=21 according to DSM-IV criteria. All the patients had a mean cholesterol level within the normal range; males (N=22 and females (N=63 had approximately the same serum cholesterol levels (p > .05. No significant differences in cholesterol levels emerged between PD, GAD and MD patient groups. Both female PD and female GAD subjects had a mean cholesterol level similar to their male counterparts (p>.05. It is concluded that both Hayward and colleagues and Bajwa et al. findings could not be replicated by our study.Foram medidos os níveis plasmáticos de colesterol total em 85 pacientes ambulatoriais com transtorno de pânico (TP; N = 41, transtorno de ansiedade generalizada (TAG; N = 23 e depressão maior (DM; N = 21, diagnosticados de acordo com os critérios do DSM-IV. O grupo de pacientes apresentou média do nível de colesterol dentro da faixa normal; homens (N = 22 e mulheres (N = 63 tiveram aproximadamente os mesmos níveis séricos de colesterol (p > 0,05. Não foram observadas diferenças nos níveis de colesterol entre os grupos de pacientes com TP, TAG e DM. Mulheres com TP e as com TAG apresentaram média dos níveis de colesterol semelhante aos seus pares masculinos (p > 0,05. Conclui-se que os resultados obtidos por Hayward et al. e por Bajwa et al. não foram replicados neste estudo.

  18. Cholesterol testing and results

    Science.gov (United States)

    Cholesterol test results; LDL test results; VLDL test results; HDL test results; Coronary risk profile results; Hyperlipidemia- ... Some cholesterol is considered good and some is considered bad. Different blood tests can be done to measure each ...

  19. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  20. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  1. Cholesterol and public policy.

    Science.gov (United States)

    LaRosa, J C

    1994-08-01

    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  2. Dieta vegetariana e níveis de colesterol e triglicérides Vegetarian diet and cholesterol and triglycerides levels

    Directory of Open Access Journals (Sweden)

    Simone Grigoletto De Biase

    2007-01-01

    Full Text Available OBJETIVO: Comparar os valores de triglicérides (TG, colesterol total (CT, lipoproteína de baixa densidade (LDL e lipoproteína de alta densidade (HDL entre indivíduos vegetarianos e onívoros. MÉTODOS: Foram coletadas amostras sangüíneas de 76 indivíduos, de ambos os sexos, que foram separados em quatro grupos de dieta: onívoro, ovolacto, lacto e vegetariano restrito (ou "vegan". Foram dosados: CT, LDL, HDL e TG. RESULTADOS: Para as taxas de CT, LDL e TG, observa-se diferença significante entre as amostras, sendo o maior valor nos onívoros, havendo decréscimo nos vegetarianos, de acordo com o grau de restrição de produtos de origem animal, sendo a menor taxa observada nos "vegans". A média e o desvio padrão do CT foram de 208,09 ± 49,09 mg/dl no grupo de onívoros, e 141,06 ± 30,56 mg/dl no de vegan (p OBJECTIVE: Compare levels of triglyceride (TG, total cholesterol (TC, low density lipoprotein (LDL and high density lipoprotein (HDL among vegetarians and omnivores. METHODS: Blood samples were collected from 76 individuals - both males and females - separated in four different diet groups: omnivores, lacto-ovo vegetarians, lacto vegetarians, and restricted vegetarians (or vegans. Dosing was done for: TC, LDL, HDL and TG. RESULTS: Significant difference was reported for TC, LDL and TG levels among the samples. Higher levels were reported by omnivores, with decreased levels for vegetarians as animal products were restricted, with lowest levels having been reported by vegans. Mean and standard deviation for TC were 208.09 ± 49.09 mg/dl in the group of omnivores, and 141.06 ± 30.56 mg/dl in the group of vegans (p < 0.001. LDL values for omnivores and vegans were respectively: 123.43 ± 42.67 mg/dl and 69.28 ± 29.53 mg/dl (p < 0.001. As for TG, those values were 155.68 ± 119.84 mg/dl and 81.67 ± 81.90 mg/dl (p < 0.01. As for HDL level no difference was reported between the samples, but HDL/TC ratio was significantly higher in

  3. Imbalanced cholesterol metabolism in Alzheimer's disease.

    Science.gov (United States)

    Xue-shan, Zhao; Juan, Peng; Qi, Wu; Zhong, Ren; Li-hong, Pan; Zhi-han, Tang; Zhi-sheng, Jiang; Gui-xue, Wang; Lu-shan, Liu

    2016-05-01

    Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

  4. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr

    2016-01-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low...... and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have...

  5. Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase

    Directory of Open Access Journals (Sweden)

    Eder de Carvalho Pincinato

    2009-09-01

    Full Text Available Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43 and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL to low density lipoproteins (LDL and very low density lipoproteins (VLDL by cholesteryl ester transfer protein (CETP was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing

  6. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  7. Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    2012-01-01

    Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. A major recognized functional property of HDL particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport (RCT). T

  8. Effects of past and recent blood pressure and cholesterol level on coronary heart disease and stroke mortality, accounting for measurement error.

    Science.gov (United States)

    Boshuizen, Hendriek C; Lanti, Mariapaola; Menotti, Alessandro; Moschandreas, Joanna; Tolonen, Hanna; Nissinen, Aulikki; Nedeljkovic, Srecko; Kafatos, Anthony; Kromhout, Daan

    2007-02-15

    The authors aimed to quantify the effects of current systolic blood pressure (SBP) and serum total cholesterol on the risk of mortality in comparison with SBP or serum cholesterol 25 years previously, taking measurement error into account. The authors reanalyzed 35-year follow-up data on mortality due to coronary heart disease and stroke among subjects aged 65 years or more from nine cohorts of the Seven Countries Study. The two-step method of Tsiatis et al. (J Am Stat Assoc 1995;90:27-37) was used to adjust for regression dilution bias, and results were compared with those obtained using more commonly applied methods of adjustment for regression dilution bias. It was found that the commonly used univariate adjustment for regression dilution bias overestimates the effects of both SBP and cholesterol compared with multivariate methods. Also, the two-step method makes better use of the information available, resulting in smaller confidence intervals. Results comparing recent and past exposure indicated that past SBP is more important than recent SBP in terms of its effect on coronary heart disease mortality, while both recent and past values seem to be important for effects of cholesterol on coronary heart disease mortality and effects of SBP on stroke mortality. Associations between serum cholesterol concentration and risk of stroke mortality are weak.

  9. Cholesterol confusion and statin controversy

    Institute of Scientific and Technical Information of China (English)

    Robert; Du; Broff; Michel; de; Lorgeril

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.

  10. Higher prevalence of smoking and lower BMI, waist circumference, cholesterol and triacylglyceride levels in Prague's homeless compared to a majority of the Czech population

    Directory of Open Access Journals (Sweden)

    Rambousková Jolana

    2007-04-01

    Full Text Available Abstract Background Homeless people have higher morbidity and mortality rates than the general population. Research has shown that cardiovascular disease is the leading cause of death in older homeless adults. This study was undertaken to describe the prevalence of cardiovascular risk factors in the homeless population in Prague. Methods Data was obtained from a cross-sectional study carried out in 2003. Body mass index (BMI, waist circumference (WC, total cholesterol (TC, triacylglycerides (TAG and smoking habits were assessed. The homeless participants in the study were recruited from a homeless center run by a Prague charitable organization called Naděje ("Hope" and at Prague's main railway station. Most participants were assessed at the Naděje center (134 persons while the rest were assessed at Prague's Bulovka University Hospital (67 persons. Results A total of 201 homeless (174 males and 27 females aged 19 – 70 years were examined. Mean values of BMI, WC, TC and TAG in homeless men and women were within normal limits. Compared with the majority of the Czech population, the homeless had significantly lower mean levels of TC and TAG and lower BMI and WC values. When compared to the majority of the Czech population, the incidence of smoking among the homeless was significantly higher. Among smokers in both populations, no differences were found in the number of cigarettes smoked per day. Conclusion Classical cardiovascular risk factors such as TC, TAG, BMI and WC, are significantly lower in Prague's homeless minority than in the majority of the Czech population. However, the prevalence of smoking is much higher in the homeless population.

  11. Effects of Kefir on Serum Cholesterol Level in Mice%开菲尔对小鼠血清胆固醇水平的影响

    Institute of Scientific and Technical Information of China (English)

    国立东; 刘倩; 刘爱芳; 刘晓艳; 于纯淼

    2014-01-01

    开菲尔是一种饮用历史悠久的功能性发酵乳制品,为探讨开菲尔对小鼠血清胆固醇水平的影响,将小鼠随机分成3组:对照组、高脂模型组和开菲尔组。对照组饲喂基础饲料,高脂模型组和开菲尔组饲喂高脂饲料,开菲尔组每日灌胃开菲尔发酵乳,对照组和高脂模型组给予无菌蒸馏水,连续灌胃28 d。结果表明,开菲尔组与高脂模型组相比,小鼠血清总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)含量明显降低(P0.05),动脉粥样硬化指数(AI)极显著降低(P0.05) differences.After kefir administration,the atherosclerotic index(AI) significantly(P<0.01)decreased,and antiatherosclerotic index(AAI)significantly(P<0.01)increased.These results suggested that kefir may be effectively in reducing serum cholesterol level in hypercholesterolemia mice.

  12. Cholesterol homeostasis: How do cells sense sterol excess?

    Science.gov (United States)

    Howe, Vicky; Sharpe, Laura J; Alexopoulos, Stephanie J; Kunze, Sarah V; Chua, Ngee Kiat; Li, Dianfan; Brown, Andrew J

    2016-09-01

    Cholesterol is vital in mammals, but toxic in excess. Consequently, elaborate molecular mechanisms have evolved to maintain this sterol within narrow limits. How cells sense excess cholesterol is an intriguing area of research. Cells sense cholesterol, and other related sterols such as oxysterols or cholesterol synthesis intermediates, and respond to changing levels through several elegant mechanisms of feedback regulation. Cholesterol sensing involves both direct binding of sterols to the homeostatic machinery located in the endoplasmic reticulum (ER), and indirect effects elicited by sterol-dependent alteration of the physical properties of membranes. Here, we examine the mechanisms employed by cells to maintain cholesterol homeostasis.

  13. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

    Science.gov (United States)

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Goulet, Amy; Moghadasian, Mohammed H

    2016-10-25

    Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

  14. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    NARCIS (Netherlands)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D; Granados-Silvestre, Ma de Angeles; Montufar-Robles, Isela; Tito-Alvarez, Ana M; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A; Lisker, Ruben; Moises, Regina S; Menjivar, Marta; Salzano, Francisco M; Knowler, William C; Bortolini, M Cátira; Hayden, Michael R; Baier, Leslie J; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was

  15. All-cause mortality in patients with type 2 diabetes in association with achieved hemoglobin A(1c, systolic blood pressure, and low-density lipoprotein cholesterol levels.

    Directory of Open Access Journals (Sweden)

    Hou-Hsien Chiang

    Full Text Available BACKGROUND: To identify the ranges of hemoglobin A(1c (HbA1c, systolic blood pressure (SBP, and low-density lipoprotein cholesterol (LDL-C levels which are associated with the lowest all-cause mortality. METHODS: A retrospective cohort of 12,643 type 2 diabetic patients (aged ≥18 years were generated from 2002 to 2010, in Far-Eastern Memorial Hospital, New Taipei city, Taiwan. Patients were identified to include any outpatient diabetes diagnosis (ICD-9: 250, and drug prescriptions that included any oral hypoglycemic agents or insulin prescribed during the 6 months following their first outpatient visit for diabetes. HbA1c, SBP, and LDL-C levels were assessed by the mean value of all available data, from index date to death or censor date. Deaths were ascertained by matching patient records with the Taiwan National Register of Deaths. RESULTS: Our results showed general U-shaped associations, where the lowest hazard ratios occurred at HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL. The risk of mortality gradually increases if the patient's mean HbA1c, SBP, or LDL-C during the follow-up period was higher or lower than these ranges. In comparison to the whole population, the adjusted hazard ratio (95% CI for patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, and LDL-C 100-130 mg/dL were 0.69 (0.62-0.77, 0.80 (0.72-0.90, and 0.68 (0.61-0.75, respectively. CONCLUSIONS: In our type 2 diabetic cohort, the patients with HbA1c 7.0-8.0%, SBP 130-140 mmHg, or LDL-C 100-130 mg/dL had the lowest all-cause mortality. Additional research is needed to confirm these associations and to further investigate their detailed mechanisms.

  16. Regulation of cholesterol homeostasis.

    Science.gov (United States)

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K

    2013-04-10

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  17. Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs : measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques

    NARCIS (Netherlands)

    Stellaard, Frans; Kuipers, Folkert

    2005-01-01

    Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake. Disturba

  18. Relationship between the Cholesterol Level in Children with Asthma and Susceptibility of Mycoplasma Pneumoniae%哮喘患儿血清胆固醇水平与易感肺炎支原体的关系

    Institute of Scientific and Technical Information of China (English)

    张长娟; 段全纪; 周清霞

    2014-01-01

    目的:探讨支气管哮喘(简称哮喘)患儿血清胆固醇水平与易感肺炎支原体( MP )的关系。方法60例哮喘患儿分为哮喘组,40例健康儿童被分为正常对照组,检测两组血清总胆固醇水平,并进行1年的随访,记录随访期内肺炎支原体感染的次数。结果哮喘患儿血清总胆固醇水平及随访期内哮喘患儿肺炎支原体感染次数明显高于对照组,( P<0.05)。结论哮喘患儿存在血清胆固醇水平升高,其可致哮喘患儿更易感染肺炎支原体。%[ ABSTRACT] Objective To discuss the relationship between the cholesterol level in children with asthma and susceptibility of Mycoplasma pneumonia ( MP ) .Methods Sixty children with asthma were divided into the asthma group,and 40 healthy volunteers were divided into the healthy control group,then the cholesterol level was contrasted be-tween the two groups.Children with asthma and healthy volunteers were followed up for 1 year,and the number of MP in-fection during the follow-up period was recorded.Results The cholesterol level and the number of MP infection in the asthma group were significantly higher than those in the healthy control group.Conclusion High cholesterol exists in children with asthma and it can make children with asthma more vulnerable to infection MP.

  19. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally...... associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores...... and allele numbers associated with up to -13 and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2 diabetes...

  20. Physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2014-01-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

  1. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    Science.gov (United States)

    Kannisto, Kristina; Gåfvels, Mats; Jiang, Zhao-Yan; Slätis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gösta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol.

  2. Effect of High-Dose Atorvastatin on Renal Function in Subjects With Stroke or Transient Ischemic Attack in the SPARCL Trial

    DEFF Research Database (Denmark)

    Amarenco, Pierre; Callahan, Alfred, III; Campese, Vito M.

    2014-01-01

    BACKGROUND AND PURPOSE: Higher low-density lipoprotein cholesterol is associated with more rapid chronic kidney disease progression; reduction in cholesterol with statins, in conjunction with statins' pleiotropic effects, such as decreasing inflammation, may be renoprotective. The Stroke Preventi...... ischemic attack with and without chronic kidney disease, and that atorvastatin treatment may prevent eGFR decline in patients with stroke and diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00147602....

  3. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  4. A church-based cholesterol education program.

    Science.gov (United States)

    Wiist, W H; Flack, J M

    1990-01-01

    The leading cause of death among black people in the United States is coronary heart disease, accounting for about 25 percent of the deaths. The Task Force on Black and Minority Health formed by the Secretary of Health and Human Services in 1985 subsequently recommended increased efforts to reduce risk factors for coronary heart disease in the black population. A stated focus of the National Heart, Lung, and Blood Institute's National Cholesterol Education Program has been that of reaching minority groups. This report describes a pilot cholesterol education program conducted in black churches by trained members of those churches. Cholesterol screening, using a Reflotron, and other coronary heart disease risk factor screening was conducted in six churches with predominantly black members and at a neighborhood library. A total of 348 persons with cholesterol levels of 200 milligrams per deciliter (mg per dl) or higher were identified. At the time of screening, all were provided brief counseling on lowering their cholesterol and were given a copy of the screening results. Half of those identified, all members of one church, were invited to attend a 6-week nutrition education class of 1 hour each week about techniques to lower blood cholesterol. Information about cholesterol was also mailed to them. They were designated as the education group. Persons in the church were trained to teach the classes. A report of the screening results was sent to the personal physicians of the remaining 174 people in other churches who had cholesterol levels of 200 mg per dl or higher. This group served as a usual care comparison group.Six months after the initial screening, members of both groups were invited for followup screening.Among the 75 percent of the education group who returned for followup screening there was a 23.4 mg per dl (10 percent) decrease in the mean cholesterol level. Thirty-six percent of the usual care group returned for followup screening; their mean cholesterol

  5. Elevated Cholesterol in the Coxiella burnetii Intracellular Niche Is Bacteriolytic

    Science.gov (United States)

    Mulye, Minal; Samanta, Dhritiman; Winfree, Seth; Heinzen, Robert A.

    2017-01-01

    ABSTRACT Coxiella burnetii is an intracellular bacterial pathogen and a significant cause of culture-negative endocarditis in the United States. Upon infection, the nascent Coxiella phagosome fuses with the host endocytic pathway to form a large lysosome-like vacuole called the parasitophorous vacuole (PV). The PV membrane is rich in sterols, and drugs perturbing host cell cholesterol homeostasis inhibit PV formation and bacterial growth. Using cholesterol supplementation of a cholesterol-free cell model system, we found smaller PVs and reduced Coxiella growth as cellular cholesterol concentration increased. Further, we observed in cells with cholesterol a significant number of nonfusogenic PVs that contained degraded bacteria, a phenotype not observed in cholesterol-free cells. Cholesterol had no effect on axenic Coxiella cultures, indicating that only intracellular bacteria are sensitive to cholesterol. Live-cell microscopy revealed that both plasma membrane-derived cholesterol and the exogenous cholesterol carrier protein low-density lipoprotein (LDL) traffic to the PV. To test the possibility that increasing PV cholesterol levels affects bacterial survival, infected cells were treated with U18666A, a drug that traps cholesterol in lysosomes and PVs. U18666A treatment led to PVs containing degraded bacteria and a significant loss in bacterial viability. The PV pH was significantly more acidic in cells with cholesterol or cells treated with U18666A, and the vacuolar ATPase inhibitor bafilomycin blocked cholesterol-induced PV acidification and bacterial death. Additionally, treatment of infected HeLa cells with several FDA-approved cholesterol-altering drugs led to a loss of bacterial viability, a phenotype also rescued by bafilomycin. Collectively, these data suggest that increasing PV cholesterol further acidifies the PV, leading to Coxiella death. PMID:28246364

  6. Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

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    Ingemar Björkhem

    2013-09-01

    Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

  7. Cholesterol and Women's Health

    Science.gov (United States)

    ... can I make to reduce my risk of cardiovascular disease? • Is there medication that can help reduce my cholesterol ... It also helps your body make vitamin D and produces the bile that helps you ...

  8. Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism.

    Science.gov (United States)

    Bochenek, W; Rodgers, J B

    1978-01-27

    Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

  9. Effect of Moderate Alcohol Consumption on Parameters of Reverse Cholesterol Transport in Postmenopausal Women

    NARCIS (Netherlands)

    Sierksma, A.; Vermunt, S.H.F.; Lankhuizen, I.M.; Gaag, M.S. van der; Scheek, L.M.; Grobbee, D.E.; Tol, A. van; Hendriks, H.F.J.

    2004-01-01

    Background: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma choles

  10. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  11. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  12. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology.

  13. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia.

    Science.gov (United States)

    Othman, Rgia A; Myrie, Semone B; Jones, Peter J H

    2013-12-01

    Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux.

  14. [Prostate cancer dependance upon cholesterol, statins and diet].

    Science.gov (United States)

    Pilch, Paweł; Radziszewski, Piotr; Maciukiewicz, Piotr

    2012-01-01

    The aim of the work is to analyze the influence of higher cholesterol and LDL level on risk of prostate cancer. The work is based on the available literature in that field. The metabolism of cholesterol is mainly regulated by the statins, which may thus inhibit prostate cancer growth. Keeping the appropriate body mass and level of cholesterol by proper diet and physical exercises may be the prophylaxis of prostate cancer.

  15. Studies on PCSK9 in the regulation of cholesterol metabolism

    OpenAIRE

    Persson, Lena

    2011-01-01

    Elevated levels of plasma cholesterol, mainly in low density lipoproteins (LDL), are a major risk factor for coronary heart disease. The level of plasma LDL cholesterol (LDL-C) is largely dependent on the number of hepatic LDL receptors (LDLRs). Increased number of LDLRs leads to higher uptake of LDL particles and lower concentration of plasma LDL-C. Proprotein convertase subtilisin Kexin Type 9 (PCSK9) is a novel key regulator in cholesterol metabolism. PCSK9 reduces the numbe...

  16. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  17. MCPIP is induced by cholesterol and participated in cholesterol-caused DNA damage in HUVEC.

    Science.gov (United States)

    Da, Jingjing; Zhuo, Ming; Qian, Minzhang

    2015-01-01

    Hypercholesterolemia is an important risk factor for atherosclerosis and cholesterol treatment would cause multiple damages, including DNA damage, on endothelial cells. In this work, we have used human umbilical vein endothelial cell line (HUVEC) to explore the mechanism of cholesterol induced damage. We have found that cholesterol treatment on HUVEC could induce the expression of MCPIP1. When given 12.5 mg/L cholesterol on HUVEC, the expression of MCPIP1 starts to increase since 4 hr after treatment and at 24 hr after treatment it could reach to 10 fold of base line level. We hypothesis this induction of MCPIP1 may contribute to the damaging process and we have used siRNA of MCPIP1 in further research. This MCPIP1 siRNA (siMCPIP) could down regulate MCPIP1 by 73.4% and when using this siRNA on HUVECs, we could see the cholesterol induced DNA damage have been reduced. We have detected DNA damage by γH2AX foci formation in nuclear, γH2AX protein level and COMET assay. Compare to cholesterol alone group, siMCPIP group shows much less γH2AX foci formation in nuclear after cholesterol treatment, less γH2AX protein level in cell and also less tail moment detected in COMET assay. We have also seen that using siMCPIP1 could result in less reactive oxygen species (ROS) in cell after cholesterol treatment. We have also seen that using siMCPIP could reduce the protein level of Nox4 and p47(phox), two major regulators in ROS production. These results suggest that MCPIP1 may play an important role in cholesterol induced damage.

  18. Smith-Lemli-Opitz syndrome produced in rats with AY 9944 treated by intravenous injection of lipoprotein cholesterol.

    Science.gov (United States)

    Chambers, C M; McLean, M P; Ness, G C

    1997-01-31

    A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol is their impaired ability to absorb cholesterol due to a deficiency of bile acids. Since intravenously administered lipoprotein cholesterol should not require bile acids for uptake into tissues, we tested the effects of this form of cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2% dietary cholesterol was most effective as it raised hepatic cholesterol levels to 1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were decreased to 760 micrograms/g. Similar responses were seen for heart, lung, kidney, and testes. Brain sterol levels were not significantly affected. AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity. Administration of dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA reductase activity to barely detectable levels. The data indicate that the combination of iv and dietary cholesterol was most effective in raising cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo cholesterol biosynthesis.

  19. Cholesterol and prostate cancer.

    Science.gov (United States)

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R

    2012-12-01

    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  20. Dietary cholesterol modulates pathogen blocking by Wolbachia.

    Directory of Open Access Journals (Sweden)

    Eric P Caragata

    Full Text Available The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This "pathogen blocking" could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV, a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2-5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking.

  1. Cholesterol content in meat of some Cyprinidae

    Directory of Open Access Journals (Sweden)

    Živković Dragić L.

    2002-01-01

    Full Text Available The aim of this paper was to examine cholesterol content in meat of five Cyprinidae species: white bream (Bllica bjoerkna L, carp bream (Abramis brama L, baltic vimba (Vimba vimba carinata Pallas, zope (Abramis balerus L and crucian carp (Carassius carassius gibelio Bloch from the river Danube. Cholesterol content was examined in the function of season factor and individual weight. Cholesterol concentration in meat of white bream carp bream, baltic vimba, zope and crucian carp is on average level below 20 mg/100 g of meat, which makes meat of these fish species nutritively very valuable. Cholesterol content is variable during the season. Its concentration in meat and in lipids is lowest during spring, during summer it increases and during autumn decreases, except in meat of white bream. Body weight has influence on cholesterol content when its concentration is expressed as % of cholesterol in lipids. Its content in lipids decreases with increasing of individual weight, except in meat of carp bream.

  2. CHOLESTEROL ASSIMILATION BY COMMERCIAL YOGHURT STARTER CULTURES

    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno

    2007-03-01

    Full Text Available The ability to in vitro cholesterol level reduction in laboratory media has been shown for numerous strains of lactic acid bacteria, but not for all strains of lactic bacteria used in the dairy industry. The aim of this work was the determination of the ability of selected thermophilic lactic acid bacteria to cholesterol assimilation during 24 h culture in MRS broth. Commercial starter cultures showed various ability to cholesterol assimilation from laboratory medium. In case of starter cultures used for production of traditional yoghurt, consisting of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, the quantity of assimilated cholesterol did not exceed 27% of its initial contents (0.7 g in 1 dm3. Starter cultures used for bioyoghurt production, containing also probiotic strains (came from Lactobacillus acidophilus species or Bifidobacterium genus assimilated from almost 18% to over 38% of cholesterol. For one monoculture of Lb. acidophilus, cholesterol assimilation ability of 49-55% was observed, despite that the number of bacterial cells in this culture was not different from number of bacteria in other cultures.

  3. Orbitofrontal cholesterol granuloma.

    Science.gov (United States)

    Chow, L P; McNab, A A

    2005-02-01

    Cholesterol granuloma of the orbital bones is a rare but readily recognisable condition. It is an osteolytic lesion with a granulomatous reaction surrounding cholesterol crystals, old haemorrhage and a fibrous capsule. There is a male preponderance and it usually occurs in young or middle-aged men. It is treatable with drainage and curettage via an orbitotomy, and craniotomy or wide bone removal is almost never required. Six cases of this condition were reviewed to highlight the typical clinical presentation, computed tomography and magnetic resonance results, and surgical management.

  4. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  5. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may...

  6. Significance of the percentage of cholesterol efflux capacity and total cholesterol efflux capacity in patients with or without coronary artery disease.

    Science.gov (United States)

    Norimatsu, Kenji; Kuwano, Takashi; Miura, Shin-Ichiro; Shimizu, Tomohiko; Shiga, Yuhei; Suematsu, Yasunori; Miyase, Yuiko; Adachi, Sen; Nakamura, Ayumi; Imaizumi, Satoshi; Iwata, Atsushi; Nishikawa, Hiroaki; Uehara, Yoshinari; Saku, Keijiro

    2017-01-01

    We hypothesized that cholesterol efflux capacity is more useful than the lipid profile as a marker of the presence and the severity of coronary artery disease (CAD). Therefore, we investigated the associations between the presence and the severity of CAD and both the percentage of cholesterol efflux capacity and total cholesterol efflux capacity and the lipid profile including the high-density lipoprotein cholesterol (HDL-C) level in patients who underwent coronary computed tomography angiography (CTA). The subjects consisted of 204 patients who were clinically suspected to have CAD and underwent CTA. We isolated HDL from plasma by ultracentrifugation and measured the percentage of cholesterol efflux capacity using (3)H-cholesterol-labeled J774 macrophage cells and calculated total cholesterol efflux capacity as follows: the percentage of cholesterol efflux capacity/100× HDL-C levels. While the percentage of cholesterol efflux capacity was not associated with the presence or the severity of CAD, total cholesterol efflux capacity and HDL-C in patients with CAD were significantly lower than those in patients without CAD. In addition, total cholesterol efflux capacity and HDL-C, but not the percentage of cholesterol efflux capacity, significantly decreased as the number of coronary arteries with significant stenosis increased. Total cholesterol efflux capacity was positively correlated with HDL-C, whereas the percentage of cholesterol efflux capacity showed only weak association. In a logistic regression analysis, the presence of CAD was independently associated with total cholesterol efflux capacity, in addition to age and gender. Finally, a receiver-operating characteristic curve analysis indicated that the areas under the curves for total cholesterol efflux capacity and HDL-C were similar. In conclusion, the percentage of cholesterol efflux capacity using the fixed amount of isolated HDL was not associated with CAD. On the other hand, the calculated total

  7. Prediction of Major Vascular Events after Stroke

    DEFF Research Database (Denmark)

    Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre

    2014-01-01

    BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study...

  8. Patterns of cholesterol metabolism: pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome.

    Science.gov (United States)

    Lupattelli, G; De Vuono, S; Mannarino, E

    2011-09-01

    Investigating cholesterol metabolism, which derives from balancing cholesterol synthesis and absorption, opens new perspectives in the pathogenesis of dyslipidemias and the metabolic syndrome (MS). Cholesterol metabolism is studied by measuring plasma levels of campesterol, sitosterol and cholestanol, that is, plant sterols which are recognised as surrogate cholesterol-absorption markers and lathosterol or squalene, that is, cholesterol precursors, which are considered surrogate cholesterol-synthesis markers. This article presents current knowledge on cholesterol synthesis and absorption, as evaluated by means of cholesterol precursors and plant sterols, and discusses patterns of cholesterol balance in the main forms of primary hyperlipidaemia and MS. Understanding the mechanism(s) underlying these patterns of cholesterol synthesis and absorption will help to predict the response to hypolipidemic treatment, which can then be tailored to ensure the maximum clinical benefit for patients.

  9. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications.

    Science.gov (United States)

    Cohn, Jeffrey S; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W S; Tandy, Sally

    2010-06-01

    A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals.

  10. Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

    Directory of Open Access Journals (Sweden)

    Beppu Fumiaki

    2012-09-01

    Full Text Available Abstract Background Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods Diabetic/obese KK-Ay mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9, which enhances intracellular degradation of LDLR in lysosomes. Conclusions Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay mice by inducing SREBP expression and reduced cholesterol uptake in the liver via

  11. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible anti-atherosc

  12. High serum total cholesterol--an indicator for monitoring cholesterol lowering efforts: U.S. adults, 2005-2006.

    Science.gov (United States)

    Schober, Susan E; Carroll, Margaret D; Lacher, David A; Hirsch, Rosemarie

    2007-12-01

    Elevated serum total cholesterol is a major and modifiable risk factor for heart disease, the lead-ing cause of death in the United States (1,2). Reducing mean total serum cholesterol levels among adults to less than 200 mg/dL and reducing the proportion who have levels of 240 mg/dL or higher to less than 17% are national Healthy People 2010 objectives (3). Age-adjusted mean serum cholesterol levels among adults aged 20-74 years declined from 222 mg/dL in 1960-1962 to 203 mg/dL in 1999-2002 (4). Among adults aged 20 years and older, the percent of the population with high serum total cholesterol levels (240 mg/dL or higher) declined from 20% during 1988-1994 to 17% during 1999-2002 (4). In individual patients, a high serum total cholesterol level indicates a potential increased risk for heart disease, but further evaluation of other risk factors and the specific components of cholesterol provide the basis for determining the need for initiating therapeutic lifestyle changes or treatment with medication (5). Low-density-lipoprotein (LDL) is the cholesterol component associated with arterial blockage, and it is the primary clinical target for cholesterol management. High-density-lipoprotein (HDL) may help to protect individuals from developing heart disease. In populations, comparisons of total cholesterol levels over time can show if population groups are experiencing improvement in cholesterol levels, and knowledge of trends in levels of total cholesterol can help identify subgroups where additional prevention efforts may be needed.

  13. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  14. Transintestinal cholesterol efflux

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Brufau, Gemma; Groen, Albert K.

    2010-01-01

    Purpose of review Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding

  15. Cholesterol: Up in Smoke.

    Science.gov (United States)

    Raloff, Janet

    1991-01-01

    Discussed is the contribution cooked meat makes to air pollution. The dozens of compounds, including cholesterol, that are released when a hamburger is grilled are described. The potential effects of these emissions on humans and the urban environment are discussed. (KR)

  16. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  17. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  18. Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

    Science.gov (United States)

    Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Ulrich, Florian; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Torres-Vázquez, Jesús; Li, Andrew C.; Miller, Yury I.

    2013-01-01

    Cholesterol is a structural component of the cell, indispensable for normal cellular function, but its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (ApoA-I) and to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that ApoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1/Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from EC and that effective cholesterol efflux is critical for proper angiogenesis. PMID:23719382

  19. Retracted: Advances in the physiological and pathological implications of cholesterol.

    Science.gov (United States)

    Cortes, Victor A; Busso, Dolores; Mardones, Pablo; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio

    2013-11-01

    Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

  20. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  1. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    P.J.W.H. Kappelle; G.M. Dallinga-Thie; R.P.F. Dullaart

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  2. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  3. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    Science.gov (United States)

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  4. Ceramide displaces cholesterol from lipid rafts and decreases the association of the cholesterol binding protein caveolin-1.

    Science.gov (United States)

    Yu, Cuijuan; Alterman, Michail; Dobrowsky, Rick T

    2005-08-01

    Addition of exogenous ceramide causes a significant displacement of cholesterol in lipid raft model membranes. However, whether ceramide-induced cholesterol displacement is sufficient to alter the protein composition of caveolin-enriched lipid raft membranes is unknown. Therefore, we examined whether increasing endogenous ceramide levels with bacterial sphingomyelinase (bSMase) depleted cholesterol and changed the protein composition of caveolin-enriched membranes (CEMs) isolated from immortalized Schwann cells. bSMase increased ceramide levels severalfold and decreased the cholesterol content of detergent-insoluble CEMs by 25-50% within 2 h. To examine the effect of ceramide on the protein composition of the CEMs, we performed a quantitative proteomic analysis using stable isotope labeling of cells in culture and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Although ceramide rapidly depleted lipid raft cholesterol, the levels of the cholesterol binding protein caveolin-1 (Cav-1) decreased by 25% only after 8 h. Importantly, replenishing the cells with cholesterol rapidly reversed the loss of Cav-1 from the CEMs. Ceramide-induced cholesterol depletion increased the association of 5'-nucleotidase and ATP synthase beta-subunit with the CEMs but had a minimal effect on changing the abundance of other lipid raft proteins, such as flotillin-1 and G-proteins. These results suggest that the ceramide-induced loss of cholesterol from CEMs may contribute to altering the lipid raft proteome.

  5. High-density lipoprotein cholesterol is a favorable prognostic factor and negatively correlated with C-reactive protein level in non-small cell lung carcinoma.

    Directory of Open Access Journals (Sweden)

    Pei-Dong Chi

    Full Text Available Although the alterations of lipid profile in lung cancer have been documented, the prognostic value of serum HDL-C level and its correlation with inflammation in NSCLC remain unknown.Levels of preoperative serum lipid concentrations (including HDL-C, LDL-C, TC, and TG and the inflammatory biomarker C-reactive protein level (CRP were retrospectively analyzed in 228 patients with NSCLC and in 300 healthy controls. The serum lipid levels in these two populations were compared. Univariate and multivariate cox hazards analyses were performed to investigate the prognostic value of serum lipid levels in NSCLC. The correlation between CRP and lipid profile were also analyzed.Compared with those in normal controls, the serum HDL-C, LDL-C, and TC levels were statistically decreased and the TG levels were significantly increased in 228 NSCLC patients. The patients with decreased levels of HDL-C had significantly lower 5-year survival rates than those with normal HDL-C, not only in the whole NSCLC cohort but also in the subgroups stratified according to the disease T, N classifications, and metastasis, whereas the other lipid components were not independent prognostic factors for NSCLC. Of the lipid components, a lower HDL-C level was observed more often in patients with a high CRP level than in those with a normal CRP level. Spearman's rank correlation analysis revealed that the HDL-C level presented a negative correlation with the CRP level (r = -0.360, p<0.001.A decreased level of preoperative HDL-C was found to be associated with poor survival in patients with NSCLC. Serum HDL-C level may be a clinical prognosis factor for NSCLC patients. In addition, a negative correlation was present between the levels of HDL-C and CRP, the well-known inflammation biomarker.

  6. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2014-01-01

    Full Text Available Excess cholesterol is associated with cardiovascular diseases (CVD, an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18 ± 0.55 mg/1010 cfu in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70 ± 63.33 mg/1010 cfu of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic.

  7. The progressive effects of a high-fat diet on erythrocyte osmotic fragility, growth performance and serum triglyceride and cholesterol levels in Guinea fowl (Numida meleagris) and Muscovy duck (Cairina moschata).

    Science.gov (United States)

    Donaldson, J; Dangarembizi, R; Mtetwa, B; Madziva, M T; Erlwanger, K H

    2014-10-01

    To investigate the progressive effects of a high-fat diet on erythrocyte osmotic fragility, growth performance and serum lipid concentrations in Guinea fowl and Muscovy ducks, 36 Guinea fowl and 36 Muscovy ducks were divided into two groups, for each species, and fed either a standard (STD = commercial poultry feed) or high-fat diet (HFD = commercial poultry feed with 20% palm oil and 2% lard) for up to 12 weeks. After 4, 8 and 12 weeks on the diets, six birds from each group were euthanized and blood samples collected. Osmotic fragility was assessed by measuring the haemoglobin released by erythrocytes placed in serially diluted solutions of phosphate-buffered saline, spectrophotometrically. Serum triglyceride and cholesterol concentrations were also determined. Fragiligrams from erythrocytes from both species of birds on the HFD were not different to those on the STD. However, Muscovy duck erythrocytes were more resistant to haemolysis compared with Guinea fowl erythrocytes. Final body mass and serum triglyceride levels were not significantly different (p > 0.05, anova) between the birds in the HFD and STD groups, for both species of birds. In contrast, serum cholesterol levels were significantly higher in birds on the HFD compared with those on the STD, after 4, 8 and 12 weeks of feeding, for both species of birds. Feeding Guinea fowl and Muscovy ducks a high-fat diet for up to 12 weeks resulted in hypercholesterolaemia but had no effect on final body mass, erythrocyte osmotic fragility or serum triglyceride concentrations in either bird species.

  8. Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7 alpha-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events

    NARCIS (Netherlands)

    Hofman, M.K.; Princen, H.M.G.; Zwinderman, A.H.; Jukema, J.W.

    2005-01-01

    CHD (coronary heart disease) is a complex disorder which is, in part, related to serum cholesterol levels. The rate-limiting enzyme in the catabolism of cholesterol into bile acids is CYP7A1 (cholesterol 7alpha-hydroxylase). The effect of the CYP7A1 A-278C promoter polymorphism on the progression of

  9. Low serum cholesterol, serotonin metabolism, and violent death

    NARCIS (Netherlands)

    P.H.A. Steegmans

    1995-01-01

    textabstractA high serum cholesterol level is a well documented risk factor for atherosclerotic cardiovascular disease. Consequently, a low serum cholesterol has in general been viewed as beneficial. However, since the early 70s, results from several cohort studies and randomized trials have suggest

  10. Cholesterol crystal embolism (atheroembolism)

    Science.gov (United States)

    VENTURELLI, CHIARA; JEANNIN, GUIDO; SOTTINI, LAURA; DALLERA, NADIA; SCOLARI, FRANCESCO

    2006-01-01

    Cholesterol crystal embolism, known as atheroembolic disease, is caused by showers of cholesterol crystals from an atherosclerotic plaque that occludes small arteries. Embolization can occur spontaneously or as an iatrogenic complication from an invasive vascular procedure (angiography or vascular surgery) and after anticoagulant therapy. The atheroembolism can give rise to different degrees of renal impairment. Some patients show a moderate loss of renal function, others severe renal failure requiring dialysis. Renal outcome can be variable: some patients deteriorate or remain on dialysis, some improve and some remain with chronic renal impairment. Clinically, three types of atheroembolic renal disease have been described: acute, subacute or chronic. More frequently a progressive loss of renal function occurs over weeks. Atheroembolization can involve the skin, gastrointestinal system and central nervous system. The diagnosis is difficult and controversial for the protean extrarenal manifestations. In the past, the diagnosis was often made post-mortem. In the last 10 yrs, awareness of atheroembolic renal disease has improved. The correct diagnosis requires the clinician to be alert. The typical patient is a white male aged >60 yrs with a history of hypertension, smoking and arterial disease. The presence of a classic triad (precipitating event, renal failure and peripheral cholesterol crystal embolization) suggests the diagnosis. This can be confirmed by a biopsy of the target organs. A specific treatment is lacking; however, it is an important diagnosis to make because an aggressive therapeutic approach can be associated with a more favorable clinical outcome. PMID:21977265

  11. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan

    2014-02-01

    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  12. Measurement of Intestinal and Peripheral Cholesterol Fluxes by a Dual-Tracer Balance Method.

    Science.gov (United States)

    Ronda, Onne A H O; van Dijk, Theo H; Verkade, H J; Groen, Albert K

    2016-12-01

    Long-term elevated plasma cholesterol levels put individuals at risk for developing atherosclerosis. Plasma cholesterol levels are determined by the balance between cholesterol input and output fluxes. Here we describe in detail the methodology to determine the different cholesterol fluxes in mice. The percentage of absorbed cholesterol is calculated from a stable isotope-based double-label method. Cholesterol synthesis is calculated from MIDA after (13) C-acetate enrichment. Cholesterol is removed from the body via the feces. The fecal excretion route is either biliary or non-biliary. The non-biliary route is dominated by trans-intestinal cholesterol efflux, or TICE. Biliary excretion of cholesterol is measured by collecting bile. Non-biliary excretion is calculated by computational modeling. In this article, we describe methods and procedures to measure and calculate dietary intake of cholesterol, fractional cholesterol absorption, fecal neutral sterol output, biliary cholesterol excretion, TICE, cholesterol synthesis, peripheral fluxes, and whole-body cholesterol balance. © 2016 by John Wiley & Sons, Inc.

  13. LDL cholesterol: controversies and future therapeutic directions.

    Science.gov (United States)

    Ridker, Paul M

    2014-08-16

    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  14. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  15. Two-compartment model as a teaching tool for cholesterol homeostasis.

    Science.gov (United States)

    Wrona, Artur; Balbus, Joanna; Hrydziuszko, Olga; Kubica, Krystian

    2015-12-01

    Cholesterol is a vital structural and functional molecule in the human body that is only slightly soluble in water and therefore does not easily travels by itself in the bloodstream. To enable cholesterol's targeted delivery to cells and tissues, it is encapsulated by different fractions of lipoproteins, complex particles containing both proteins and lipids. Maintaining cholesterol homeostasis is a highly regulated process with multiple factors acting at both molecular and tissue levels. Furthermore, to regulate the circulatory transport of cholesterol in lipoproteins, the amount of cholesterol present depends on and is controlled by cholesterol dietary intake, de novo synthesis, usage, and excretion; abnormal and/or unbalanced cholesterol levels have been shown to lead to severe outcomes, e.g., cardiovascular diseases. To investigate cholesterol transport in the circulatory system, we have previously developed a two-compartment mathematical model. Here, we show how this model can be used as a teaching tool for cholesterol homeostasis. Using the model and a hands-on approach, students can familiarize themselves with the basic components and mechanisms behind balanced cholesterol circulatory transport as well as investigate the consequences of and countermeasures to abnormal cholesterol levels. Among others, various treatments of high blood cholesterol levels can be simulated, e.g., with commonly prescribed de novo cholesterol synthesis inhibitors.

  16. Blood cholesterol, a public health perspective.

    NARCIS (Netherlands)

    Verschuren, W.M.M.

    1995-01-01

    Changes in total cholesterol levels (TC) were studied using data from three epidemiological studies: about 30,000 men and women aged 37-43 were examined between 1974 and 1980 (CB Project), about 80,000 men aged 33-37 between 1981 and 1986 (RIFOH Project) and 42,000 men and women aged 20-59 from 1987

  17. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo

    2009-01-01

    Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins....... In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

  18. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...... in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant......, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...

  19. Enhancing reverse cholesterol transport/raising HDL cholesterol : new options for prevention and treatment of cardiovascular disease

    NARCIS (Netherlands)

    Jukema, J W; Lenselink, M; de Grooth, G J; Boekholdt, S M; Liem, A H; Kuivenhoven, J-A; Kastelein, J J P

    2004-01-01

    High-density lipoprotein cholesterol (HDL-c) plays a crucial role in the concept of reverse cholesterol transport and has many other beneficial properties which may interfere with atherogenesis and plaque rupture. Low HDL-c levels are currently considered to be an important risk factor for the devel

  20. Cholesterol accumulation in prostate cancer: a classic observation from a modern perspective.

    Science.gov (United States)

    Krycer, James Robert; Brown, Andrew John

    2013-04-01

    Prostate cancer (PCa) is the most common cancer in men in developed countries. Epidemiological studies have associated high blood-cholesterol levels with an increased risk of PCa, whilst cholesterol-lowering drugs (statins) reduce the risk of advanced PCa. Furthermore, normal prostate epithelial cells have an abnormally high cholesterol content, with cholesterol levels increasing further during progression to PCa. In this review, we explore why and how this occurs. Concurrent to this observation, intense efforts have been expended in cardiovascular research to better understand the regulators of cholesterol homeostasis. Here, we apply this knowledge to elucidate the molecular mechanisms driving the accumulation of cholesterol in PCa. For instance, recent evidence from our group and others shows that major signalling players in prostate growth and differentiation, such as androgens and Akt, modulate the key transcriptional regulators of cholesterol homeostasis to enhance cholesterol levels. This includes adjusting central carbon metabolism to sustain greater lipid synthesis. Perturbations in cholesterol homeostasis appear to be maintained even when PCa approaches the advanced, 'castration-resistant' state. Overall, this provides a link between cholesterol accumulation and PCa cell growth. Given there is currently no cure for castration-resistant PCa, could cholesterol metabolism be a novel target for PCa therapy? Overall, this review presents a picture that cholesterol metabolism is important for PCa development: growth-promoting factors stimulate cholesterol accumulation, which in turn presents a possible target for chemotherapy. Consequently, we recommend future investigations, both to better elucidate the mechanisms driving this accumulation and applying it in novel chemotherapeutic strategies.

  1. Bad cholesterol and good mood: exploring the link

    Directory of Open Access Journals (Sweden)

    Yashaswi Gupta

    2016-01-01

    Full Text Available It is a well-known fact that high cholesterol increases the risks of heart disease. Hence, physicians actively encourage cholesterol-lowering interventions using medications and lifestyle modifications. However, there is considerable evidence that aggressive lowering of cholesterol is associated with depression, bipolar disorders, violent behaviour, and suicidal ideation. It has been hypothesised that low cholesterol leads to low levels of serotonin, a chemical that is responsible for maintaining mood balance. South Korea and India have highest number of suicides in Asia. It is a significant challenge for physicians to search an alternative that will not only maintain healthy level of cholesterol, but also contribute to psychological well-being of the patient. Generally, the role of diet and physical activity is considered secondary to medications. However, dietary supplements like coenzyme Q10 (CoQ10, omega-3 fatty acids, niacin, and physical activity like Yoga are extremely beneficial for improving lipid profile and symptoms of depression.

  2. Relative and cumulative effects of lipid and blood pressure control in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial

    DEFF Research Database (Denmark)

    Amarenco, Pierre; Goldstein, Larry B; Messig, Michael

    2009-01-01

    randomized 4731 patients with recent stroke or transient ischemic attack and no known coronary heart disease to atorvastatin 80 mg per day or placebo. RESULTS: After 4.9 years, at each level of LDL-C reduction, subjects with HDL-C value above the median or systolic BP below the median had greater reductions...

  3. Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4

    NARCIS (Netherlands)

    Mulder, M.; Ravid, R.; Kloet, J.E.R. de; Haasdijk, E.D.; Julk, J.; Boom, J. van der; Havekes, L.M.

    1998-01-01

    Apolipoprotein E4 (apoE4) has been identified as a major risk factor for Alzheimer disease (AD). Previously it has been reported that levels of apoE are reduced in cerebrospinal fluid (CSF) of AD patients. Because it is known that apoE4 affectss plasma lipid metabolism we examined whether the presen

  4. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    DEFF Research Database (Denmark)

    Van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris;

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel crea...

  5. Efeito de probiótico na modulação dos níveis de colesterol sérico e no peso do fígado de ratos alimentados com dieta rica em colesterol e ácido cólico Evaluation of the probiotic effect in the modulation of the levels of seric cholesterol and in the weight of the liver of mices fed with rich diet in cholesterol and colic acid

    Directory of Open Access Journals (Sweden)

    Dayse Fontes Machado

    2003-08-01

    Full Text Available Alimentos contendo probióticos são conhecidos como funcionais e têm sido recomendados para indivíduos com hipercolesterolemia. Com o objetivo de avaliar seu efeito na modulação dos níveis de colesterol sérico, foi conduzido um estudo de 28 dias, utilizando-se 90 ratos machos Wistar, distribuídos entre os tratamentos: Padrão, com 30 animais e Controle, LDR (Leite Desnatado Reconstituído e P (Probiótico, com 20 animais cada. O grupo Padrão recebeu a dieta AIN-93G durante todo o período experimental. Os demais grupos receberam a mesma dieta acrescida de 1% de colesterol e 0,1% de ácido cólico. Do 15º ao 28º dia, o grupo LDR recebeu 0,1mL/dia/animal de leite desnatado reconstituído a 10% de sólidos não gordurosos e o grupo P, recebeu 0,1mL/dia/animal de probiótico contendo 10(10 UFC/mL de Lactobacillus acidophilus NCFM. Avaliou-se o colesterol total, LDL-colesterol e HDL-colesterol e o peso do fígado, imediatamente após o término da administração do probiótico, onde os ratos tiveram o fígado retirado e o sangue coletado por punção cardíaca. A adição de colesterol e ácido cólico à dieta não elevou (p>0,05 os níveis de colesterol do grupo Controle, LDR e P em relação ao grupo Padrão, no entanto, promoveu aumento significativo de peso (p0,05 os níveis de colesterol sérico dos animais, uma vez que estes níveis se mantiveram normais durante todo o período experimental. Observou-se também que a administração de probiótico não impediu o acúmulo de gordura no fígado dos animais que receberam dieta rica em colesterol e ácido cólico.Probiotics are known as functional foods and have been recommended as dietary adjunct for individuals with high serum cholesterol levels. To evaluate probiotics effects on the modulation of serum cholesterol an experiment was carried out during 28 days, using 90 Wistar male rats, distributed in four treatments and individually housed, with initial average weight of 250±32g

  6. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  7. Cholesterol metabolism in Huntington disease.

    Science.gov (United States)

    Karasinska, Joanna M; Hayden, Michael R

    2011-09-06

    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  8. Cholesterol Embolism: An Overlooked Diagnosis

    Directory of Open Access Journals (Sweden)

    Sinem Nihal ESATOĞLU

    2012-01-01

    Full Text Available Acute renal failure following angiography is usually due to radiocontrast nephropathy; however, cholesterol embolism should be kept in mind when making the differential diagnosis. Cholesterol embolism is a multisystem disease, usually seen in elderly men who have severe atherosclerosis. In this case report, we describe a patient with cholesterol embolism who had a typical clinical history of progressive renal failure. We hope that this case report will emphasize the importance of this overlooked syndrome.

  9. Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine.

    Science.gov (United States)

    Nakano, Takanari; Inoue, Ikuo; Takenaka, Yasuhiro; Ono, Hiraku; Katayama, Shigehiro; Awata, Takuya; Murakoshi, Takayuki

    2016-01-01

    Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1), an apical membrane cholesterol transporter of enterocytes, thereby reduces intestinal cholesterol absorption. This treatment also increases extrahepatic reverse cholesterol transport via an undefined mechanism. To explore this, we employed a trans-intestinal cholesterol efflux (TICE) assay, which directly detects circulation-to-intestinal lumen 3H-cholesterol transit in a cannulated jejunal segment, and found an increase of TICE by 45%. To examine whether such increase in efflux occurs at the intestinal brush border membrane(BBM)-level, we performed luminal perfusion assays, similar to TICE but the jejunal wall was labelled with orally-given 3H-cholesterol, and determined elevated BBM-to-lumen cholesterol efflux by 3.5-fold with ezetimibe. Such increased efflux probably promotes circulation-to-lumen cholesterol transit eventually; thus increases TICE. Next, we wondered how inhibition of NPC1L1, an influx transporter, resulted in increased efflux. When we traced orally-given 3H-cholesterol in mice, we found that lumen-to-BBM 3H-cholesterol transit was rapid and less sensitive to ezetimibe treatment. Comparison of the efflux and fractional cholesterol absorption revealed an inverse correlation, indicating the efflux as an opposite-regulatory factor for cholesterol absorption efficiency and counteracting to the naturally-occurring rapid cholesterol influx to the BBM. These suggest that the ezetimibe-stimulated increased efflux is crucial in reducing cholesterol absorption. Ezetimibe-induced increase in cholesterol efflux was approximately 2.5-fold greater in mice having endogenous ATP-binding cassette G5/G8 heterodimer, the major sterol efflux transporter of enterocytes, than the knockout counterparts, suggesting that the heterodimer confers additional rapid BBM-to-lumen cholesterol efflux in response to NPC1L1 inhibition. The observed framework for intestinal cholesterol fluxes may provide ways to modulate the flux

  10. Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine.

    Directory of Open Access Journals (Sweden)

    Takanari Nakano

    Full Text Available Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1, an apical membrane cholesterol transporter of enterocytes, thereby reduces intestinal cholesterol absorption. This treatment also increases extrahepatic reverse cholesterol transport via an undefined mechanism. To explore this, we employed a trans-intestinal cholesterol efflux (TICE assay, which directly detects circulation-to-intestinal lumen 3H-cholesterol transit in a cannulated jejunal segment, and found an increase of TICE by 45%. To examine whether such increase in efflux occurs at the intestinal brush border membrane(BBM-level, we performed luminal perfusion assays, similar to TICE but the jejunal wall was labelled with orally-given 3H-cholesterol, and determined elevated BBM-to-lumen cholesterol efflux by 3.5-fold with ezetimibe. Such increased efflux probably promotes circulation-to-lumen cholesterol transit eventually; thus increases TICE. Next, we wondered how inhibition of NPC1L1, an influx transporter, resulted in increased efflux. When we traced orally-given 3H-cholesterol in mice, we found that lumen-to-BBM 3H-cholesterol transit was rapid and less sensitive to ezetimibe treatment. Comparison of the efflux and fractional cholesterol absorption revealed an inverse correlation, indicating the efflux as an opposite-regulatory factor for cholesterol absorption efficiency and counteracting to the naturally-occurring rapid cholesterol influx to the BBM. These suggest that the ezetimibe-stimulated increased efflux is crucial in reducing cholesterol absorption. Ezetimibe-induced increase in cholesterol efflux was approximately 2.5-fold greater in mice having endogenous ATP-binding cassette G5/G8 heterodimer, the major sterol efflux transporter of enterocytes, than the knockout counterparts, suggesting that the heterodimer confers additional rapid BBM-to-lumen cholesterol efflux in response to NPC1L1 inhibition. The observed framework for intestinal cholesterol fluxes may provide ways to

  11. The response of the prostate to circulating cholesterol: activating transcription factor 3 (ATF3 as a prominent node in a cholesterol-sensing network.

    Directory of Open Access Journals (Sweden)

    Jayoung Kim

    Full Text Available Elevated circulating cholesterol is a systemic risk factor for cardiovascular disease and metabolic syndrome, however the manner in which the normal prostate responds to variations in cholesterol levels is poorly understood. In this study we addressed the molecular and cellular effects of elevated and suppressed levels of circulating cholesterol on the normal prostate. Integrated bioinformatic analysis was performed using DNA microarray data from two experimental formats: (1 ventral prostate from male mice with chronically elevated circulating cholesterol and (2 human prostate cells exposed acutely to cholesterol depletion. A cholesterol-sensitive gene expression network was constructed from these data and the transcription factor ATF3 was identified as a prominent node in the network. Validation experiments confirmed that elevated cholesterol reduced ATF3 expression and enhanced proliferation of prostate cells, while cholesterol depletion increased ATF3 levels and inhibited proliferation. Cholesterol reduction in vivo alleviated dense lymphomononuclear infiltrates in the periprostatic adipose tissue, which were closely associated with nerve tracts and blood vessels. These findings open new perspectives on the role of cholesterol in prostate health, and provide a novel role for ATF3, and associated proteins within a large signaling network, as a cholesterol-sensing mechanism.

  12. Regulation of cerebral cholesterol metabolism in Alzheimer disease.

    Science.gov (United States)

    Reiss, Allison B; Voloshyna, Iryna

    2012-03-01

    Alzheimer disease (AD) is an age-related neurodegenerative disorder that manifests as a progressive loss of memory and deterioration of higher cognitive functions. Alzheimer disease is characterized by accumulation in the brain of the β-amyloid peptide generated by β- and γ-secretase processing of amyloid precursor protein. Epidemiological studies have linked elevated plasma cholesterol and lipoprotein levels in midlife with AD development. Cholesterol-fed animal models exhibit neuropathologic features of AD including accumulation of β-amyloid peptide. Specific isoforms of the cholesterol transporter apolipoprotein E are associated with susceptibility to AD. Although multiple lines of evidence indicate a role for cholesterol in AD, the exact impact and mechanisms involved remain largely unknown. This review summarizes the current state of our knowledge of the influence of cholesterol and lipid pathways in AD pathogenesis in vitro and in vivo.

  13. Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines.

    Science.gov (United States)

    Cerda, S R; Wilkinson, J; Broitman, S A

    1995-12-01

    Colon tumor cells, unlike normal human fibroblasts, exhibited an uncoupling of low density lipoprotein (LDL)-derived cholesterol from cellular growth, when endogenous cholesterol synthesis was inhibited by mevinolin, a hydroxymethylglutaryl-CoA reductase (HMG-CoAR) competitive inhibitor [Fabricant, M., and Broitman, S.A. (1990) Cancer Res. 50, 632-636]. Further evaluation of cholesterol metabolism was conducted in two undifferentiated (SW480, SW1417) and two differentiated (HT29, CACO2) colonic adenocarcinoma (adeno-CA) cell lines and an untransformed human fibroblast, AG1519A. Cells grown in monolayer culture to near subconfluency were used to assess endogenous cholesterol synthesis by 14C-acetate incorporation, in response to the following treatments in lipoprotein-deficient serum (LPDS)-supplemented minimum essential medium (MEM): LPDS alone, LDL, mevinolin, mevinolin with LDL, and 25-hydroxy-cholesterol (25-OH-CH). Complete fetal bovine serum (FBS)-supplemented MEM was used as control. All colon tumor lines exhibited similarly high endogenous cholesterol synthesis in both FBS and LPDS relative to the fibroblasts which demonstrated low basal levels in FBS and maximal synthesis in LPDS. LDL treatment did not inhibit cholesterol synthesis in colon tumor cells, but suppressed that in the fibroblast by 70%. Sterol repression of cholesterol synthesis mediated by 25-OH-CH occurred in all cells. Mevinolin caused a reduction in cholesterol synthesis in the colonic cancer cell lines, which was not further decreased by concurrent addition of LDL. In contrast, in mevinolin-treated fibroblasts, LDL further inhibited cholesterol synthesis. When the effect of cell density on cholesterol synthesis regulation was evaluated under conditions of sparse density in SW480 and SW147, results indicated that (i) basal rates of cholesterol synthesis were higher, (ii) LDL inhibited cholesterol synthesis more effectively, and (iii) mevinolin or 25-OH-CH had a more pronounced effect than in

  14. Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

    Science.gov (United States)

    Kallio, M J; Salmenperä, L; Siimes, M A; Perheentupa, J; Gylling, H; Miettinen, T A

    1997-04-01

    Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

  15. Assimilation (in vitro) of cholesterol by yogurt bacteria.

    Science.gov (United States)

    Dilmi-Bouras, Abdelkader

    2006-01-01

    A considerable variation is noticed between the different species studied and even between the strains of the same species, in the assimilation of cholesterol in synthetic media, in presence of different concentrations of bile salts and under anaerobiosis conditions. The obtained results show that certain strains of Streptococcus thermophilus and Lactobacillus bulgaricus resist bile salts and assimilate appreciable cholesterol quantities in their presence. The study of associations shows that only strains assimilating cholesterol in a pure state remain active when they are put in associations, but there is no additional effect. However, the symbiotic effect between Streptococcus thermophilus and Lactobacillus bulgaricus of yogurt, with regard to bile salts, is confirmed. The lactic fermenters of yogurt (Y2) reduce the levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, in a well-balanced way. In all cases, the assimilated quantity of HDL-cholesterol is lower than that of LDL-cholesterol. Moreover, yogurt Y2 keeps a significant number of bacteria, superior to 10(8) cells ml(-1), and has a good taste 10 days after its production.

  16. Food combinations for cholesterol lowering.

    Science.gov (United States)

    Harland, Janice I

    2012-12-01

    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  17. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    Science.gov (United States)

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies.

  18. Serum cholesterol and nigrostriatal R2* values in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Guangwei Du

    Full Text Available BACKGROUND: The occurrence of Parkinson's disease (PD is known to be associated both with increased nigrostriatal iron content and with low serum cholesterol and PD, but there has been no study to determine a potential relationship between these two factors. METHODS: High-resolution MRI (T1-, T2, and multiple echo T2*-weighted imaging and fasting lipid levels were obtained from 40 patients with PD and 29 healthy controls. Iron content was estimated from mean R2* values (R2* = 1/T2* calculated for each nigrostriatal structure including substantia nigra, caudate, putamen, and globus pallidus. This was correlated with serum cholesterol levels after controlling for age, gender, and statin use. RESULTS: In patients with PD, higher serum cholesterol levels were associated with lower iron content in the substantia nigra (R = -0.43, p = 0.011 for total-cholesterol, R = -0.31, p = 0.080 for low-density lipoprotein and globus pallidus (R = -0.38, p = 0.028 for total-cholesterol, R = -0.27, p = 0.127 for low-density lipoprotein, but only a trend toward significant association of higher total-cholesterol with lower iron content in the striatum (R = -0.34, p = 0.052 for caudate; R = -0.32, p = 0.061 for putamen. After adjusting for clinical measures, the cholesterol-iron relationships held or became even stronger in the substantia nigra and globus pallidus, but weaker in the caudate and putamen. There was no significant association between serum cholesterol levels and nigrostriatal iron content for controls. CONCLUSIONS: The data show that higher serum total-cholesterol concentration is associated with lower iron content in substantia nigra and globus pallidus in Parkinson's disease patients. Further studies should investigate whether this is mechanistic or epiphenomenological relationship.

  19. Hypocholesterolemic Effects of Lactic Acid-Fermented Soymilk on Rats Fed a High Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Mitsuru Fukuda

    2012-09-01

    Full Text Available The effect of fermented soymilk on rats fed a high cholesterol diet was investigated to clarify the cholesterol-lowering function. Male Sprague-Dawley rats aged 7 weeks were fed a control diet (1% cholesterol, high cholesterol diet, high cholesterol diet containing 11.7% fermented soymilk diet (5% soy protein as final concentration, F-5, or high cholesterol diet containing 23.4% fermented soymilk diet (10% soy protein as final concentration, F-10 for 5 weeks. The liver weight and fat mass were decreased by the ingestion of fermented soymilk. The hepatic triglyceride and cholesterol levels in the F-5 and F-10 groups were significantly lowered compared to those in the control group. The plasma total cholesterol level of the F-10 group was significantly decreased. The expression of SREBP-2, a cholesterol synthesis-related gene, was significantly decreased in liver of the F-5 group, but the expression of CYP7a1, a cholesterol catabolism-related gene, was significantly increased. These results suggest that fermented soymilk can modulate the cholesterol metabolism in rats fed a high cholesterol diet.

  20. Brain-derived neurotrophic factor regulates cholesterol metabolism for synapse development.

    Science.gov (United States)

    Suzuki, Shingo; Kiyosue, Kazuyuki; Hazama, Shunsuke; Ogura, Akihiko; Kashihara, Megumi; Hara, Tomoko; Koshimizu, Hisatsugu; Kojima, Masami

    2007-06-13

    Brain-derived neurotrophic factor (BDNF) exerts multiple biological functions in the CNS. Although BDNF can control transcription and protein synthesis, it still remains open to question whether BDNF regulates lipid biosynthesis. Here we show that BDNF elicits cholesterol biosynthesis in cultured cortical and hippocampal neurons. Importantly, BDNF elicited cholesterol synthesis in neurons, but not in glial cells. Quantitative reverse transcriptase-PCR revealed that BDNF stimulated the transcription of enzymes in the cholesterol biosynthetic pathway. BDNF-induced cholesterol increases were blocked by specific inhibitors of cholesterol synthesis, mevastatin and zaragozic acid, suggesting that BDNF stimulates de novo synthesis of cholesterol rather than the incorporation of extracellular cholesterol. Because cholesterol is a major component of lipid rafts, we investigated whether BDNF would increase the cholesterol content in lipid rafts or nonraft membrane domains. Interestingly, the BDNF-mediated increase in cholesterol occurred in rafts, but not in nonrafts, suggesting that BDNF promotes the development of neuronal lipid rafts. Consistent with this notion, BDNF raised the level of the lipid raft marker protein caveolin-2 in rafts. Remarkably, BDNF increased the levels of presynaptic proteins in lipid rafts, but not in nonrafts. An electrophysiological study revealed that BDNF-dependent cholesterol biosynthesis plays an important role for the development of a readily releasable pool of synaptic vesicles. Together, these results suggest a novel role for BDNF in cholesterol metabolism and synapse development.

  1. Top Five Lifestyle Changes to Reduce Cholesterol

    Science.gov (United States)

    Top 5 lifestyle changes to improve your cholesterol Lifestyle changes can help reduce cholesterol, keep you off cholesterol-lowering medications or enhance the effect of your medications. Here are five lifestyle ...

  2. Understand Your Risk for High Cholesterol

    Science.gov (United States)

    ... Aortic Aneurysm More Understand Your Risk for High Cholesterol Updated:Apr 1,2016 LDL (bad) cholesterol is ... content was last reviewed on 04/21/2014. Cholesterol Guidelines: Putting the pieces together Myth vs. Truth – ...

  3. How Is High Blood Cholesterol Treated?

    Science.gov (United States)

    ... the NHLBI on Twitter. How Is High Blood Cholesterol Treated? High blood cholesterol is treated with lifestyle ... need to follow a heart healthy diet . Lowering Cholesterol Using Therapeutic Lifestyle Changes TLC is a set ...

  4. Low HDL cholesterol, aggression and altered central serotonergic activity.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  5. Cholesterol Level: Can It Be Too Low?

    Science.gov (United States)

    ... AJ, et al. Statins use and risk of depression: A systematic review and meta-analysis. Journal of Affective Disorders. 2014;160:62. Oct. 30, 2015 Original article: http://www.mayoclinic.org/diseases-conditions/high-blood- ...

  6. 化疗对乳腺癌患者血清总胆固醇及甘油三酯水平的影响%Inlfuence of Chemotherapy on The Level of Total Serum Cholesterol and Triglycerides of Breast Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    董苑梅

    2013-01-01

    Objective: To study and investigate the influence of chemotherapy on the level of total serum cholesterol and triglycerides of breast cancer patients and its clinical significance. Methods:The changes of total serum cholesterol and triglycerides of 128 breast cancer patients before and after chemotherapy and its related factors were analyzed, and at the same time collected 100 cases of healthy physical examination as control group. Results: Compared with control group, the total serum cholesterol was lower, and triglycerides were no obvious different. With the chemotherapy time increased, the total serum cholesterol in patients rose obviously, there is significant difference with that before treatment;And there were no significant difference of triglycerides level before and after chemotherapy. Various chemotherapy regimens didn’t affect the level of total serum cholesterol and triglycerides. Conclusion:The level of total serum cholesterol and triglycerides of breast cancer patients are low relatively, as chemotherapy time goes on, the total serum cholesterol in patients rise gradually, and there are no obvious changes of triglycerides.%目的:研究探讨化疗对乳腺癌患者血清总胆固醇及甘油三酯水平的影响及临床意义。方法:对我院128例乳腺癌患者化疗前后的血清总胆固醇及甘油三酯变化和相关因素进行分析,同时收集100例健康体检者作为对照组分析。结果:血清总胆固醇检测量与对照组相比偏低,甘油三脂无明显差异。随着化疗时间的增加,患者的血清总胆固醇升高较为明显,与化疗前相比有明显差异;甘油三脂水平化疗前后无明显差异,不具有统计学意义。另外各种化疗方案对血清总胆固醇和甘油三脂的影响无差异。结论:乳腺癌患者血清总胆固醇相对较低,随着化疗时间增长患者的血清总胆固醇也逐步升高,而对患者的甘油三脂水平影响不明显。

  7. Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids

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    Weir Jacquelyn M

    2010-12-01

    Full Text Available Abstract Background Milk phospholipids (PLs reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake. Methods Mice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated: a a PL-rich dairy milk extract (PLRDME, and b a commercially-available milk PL concentrate (PC-700. Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS. Results Both PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, P 14C]cholesterol was significantly less (-30% to -60%, P 14C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, P 14C]cholesterol (P 14C]cholesterol (P P P Conclusion These results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.

  8. Clinical significance of serum cholesterol levels in multiple myeloma%多发性骨髓瘤患者血清胆固醇水平的临床意义

    Institute of Scientific and Technical Information of China (English)

    贺白; 曹祥山; 顾伟英; 谢晓宝; 吴炜; 钱新瑜; 华晓莹; 严峰; 李海乾

    2010-01-01

    目的 探讨多发性骨髓瘤(MM)患者血清胆固醇水平变化及其与分型、分期的关系.方法 回顾分析65例MM患者诊断时血脂水平,包括总胆固醇(TC)、三酰什油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(Apo-A1)和载脂蛋白B(Apo-B),探讨血脂参数与MM患者免疫球蛋白类型和临床分期关系.以健康体检者30例作为对照组.结果 65例MM患者中IgG型35例(53.85%),Ⅲ期41例(63.1%),MM患者血清TC、HDL-C、LDL-C、Apo-A1和Apo-B明显低于对照组(P0.05);除1例IgD型外,其余64例患者中,IsG和IgA型患者血清TC、HDL-C、LDL-C、Apo-Al和Apo-B均显著低于轻链型(P0.05). Except one case of IgD type, the levels of TC, HDL-C, LDL-C, apo Al and apo B in Ig G and Ig A types of patients were significantly lower than that in the light chain type among other 64 cases (P <0.05), and TG levels in different immunoglobulin types was found no statistical differences. The levels of TC, HDL-C, LDL-C and apo A1 in the patients with stage Ⅲ were lower than that of stage I and controls (P <0.05), furthermore, the level of LDL in stage Ⅱwas lower than that in stage Ⅰ. Conclusion Hypocholesterolemia are seen in the patients with MM and serum cholesterol levels are related to MM staging.

  9. Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xin-ting WANG; Jia LI; Li LIU; Nan HU; Shi JIN; Can LIU; Dan MEI; Xiao-dong LIU

    2012-01-01

    Aim:Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions.The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications.Methods:Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats.On d 35 after the injection,liver,heart,intestine,kidney,pancreas,cerebral cortex and hippocampus were isolated from the rats.The content of total and free cholesterol in the tissues was determined using HPLC.The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses,respectively.Results:In diabetic rats,the level of free cholesterol was significantly decreased in the peripheral tissues,but significantly elevated in hippocampus,as compared with those in the control rats.Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues,but significant change was only found in kidney and liver.In diabetic rats,the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex,but the change had no statistical significance.Conclusion:Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus.The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

  10. The cholesterol lowering property of coriander seeds (Coriandrum sativum): mechanism of action.

    Science.gov (United States)

    Dhanapakiam, P; Joseph, J Mini; Ramaswamy, V K; Moorthi, M; Kumar, A Senthil

    2008-01-01

    Coriandrum sativum (Coriander) has been documented as a traditional treatment for cholesterol and diabetes patients. In the present study, coriander seeds incorporated into diet and the effect of the administration of coriander seeds on the metabolism of lipids was studied in rats, fed with high fat diet and added cholesterol. The seeds had a significant hypolipidemic action. In the experimental group of rats (tissue) the level of total cholesterol and triglycerides increased significantly There was significant increase in beta-hydroxy, beta-methyl glutaryl CoA reductase and plasma lecithin cholesterol acyl transferase activity were noted in the experimental group. The level of low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol decreased while that of high density lipoprotein (HDL) cholesterol increased in the experimental group compared to the control group. The increased activity of plasma LCAT enhanced degradation of cholesterol to fecal bile acids and neutral sterols appeared to account for its hypocholesterolemic effect.

  11. Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Mahla, G; Muller, D; Pentrup, A; Black, D M

    1998-01-01

    BACKGROUND: High levels of total and LDL-cholesterol are associated with an increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol levels by pharmacologic intervention with inhibitors of cholesterol synthesis, the so-called statins, reduces the incidence of cardiovascular

  12. Alternative to decrease cholesterol in sheep milk cheeses.

    Science.gov (United States)

    Gómez-Cortés, P; Viturro, E; Juárez, M; de la Fuente, M A

    2015-12-01

    The presence of cholesterol in foods is of nutritional interest because high levels of this molecule in human plasma are associated with an increasing risk of cardiovascular disease and nowadays consumers are demanding healthier products. The goal of this experiment was to diminish the cholesterol content of Manchego, the most popular Spanish cheese manufactured from ewes milk. For this purpose three bulk milks coming from dairy ewe fed with 0 (Control), 3 and 6% of linseed supplement on their diet were used. Nine cheeses (3 per bulk milk) were manufactured and ripened for 3 months. Cholesterol of ewes milk cheese from 6% to 12% linseed supplemented diets decreased by 9.6% and 16.1% respectively, therefore supplying a healthier profile. In a second experiment, different sources of unsaturated fatty acids (rich in oleic, linoleic and α-linolenic acids) were supplemented to dairy ewes and no significant differences were found on cheese cholesterol levels.

  13. Sesamin Enhances Cholesterol Efflux in RAW264.7 Macrophages

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    Nan Liu

    2014-06-01

    Full Text Available Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL in RAW264.7 cells. Treatment with sesamin (10 μM significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL. Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  14. Sesamin enhances cholesterol efflux in RAW264.7 macrophages.

    Science.gov (United States)

    Liu, Nan; Wu, Chongming; Sun, Lizhong; Zheng, Jun; Guo, Peng

    2014-06-06

    Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 μM) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  15. Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice

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    Yin Lu

    2012-01-01

    Full Text Available Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, triglyceride, glucose, and hepatic cholesterol storage were determined. Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24±7.94% (P<0.0001 with 5 mg/kg allicin, 39.28±5.03% (P<0.0001 with 10 mg/kg allicin, and 41.18±5.00% (P<0.0001 with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.

  16. Regulation of Cerebral Cholesterol Metabolism in Alzheimer’s Disease

    OpenAIRE

    Reiss, Allison B; Voloshyna, Iryna

    2012-01-01

    Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that manifests as a progressive loss of memory and deterioration of higher cognitive functions. AD is characterized by accumulation in the brain of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of amyloid precursor protein (APP). Epidemiological studies have linked elevated plasma cholesterol and lipoprotein levels in mid-life with AD development. Cholesterol-fed animal models exhibit neuropathologic...

  17. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

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    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  18. Role of cholesterol 7alpha-hydroxylase (CYP7A1) in nutrigenetics and pharmacogenetics of cholesterol lowering.

    Science.gov (United States)

    Hubacek, Jaroslav A; Bobkova, Dagmar

    2006-01-01

    The relationship between dietary composition/cholesterol-lowering therapy and final plasma lipid levels is to some extent genetically determined. It is clear that these responses are under polygenic control, with multiple variants in many genes participating in the total effect (and with each gene contributing a relatively small effect). Using different experimental approaches, several candidate genes have been analyzed to date.Interesting and consistent results have been published recently regarding the A-204C promoter variant in the cholesterol 7alpha-hydroxylase (CYP7A1) gene. CYP7A1 is a rate-limiting enzyme in bile acid synthesis and therefore plays an important role in maintaining cholesterol homeostasis. CYP7A1-204CC homozygotes have the greatest decrease in total cholesterol level in response to dietary changes in different types of dietary intervention studies. In contrast, one study has reported that the effect of statins in lowering low-density lipoprotein (LDL)-cholesterol levels was slightly greater in -204AA homozygotes. The CYP7A1 A-204C variant accounts for a significant proportion of the genetic predisposition of the response of plasma cholesterol levels.

  19. High-density lipoproteincholesterol, reverse cholesterol transport, and cardiovascular risk: a tale of genetics?

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    Giovanni Cimmino

    2013-10-01

    Full Text Available Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for the influx and accumulation of cholesterol in the arterial wall, while high-density lipoprotein (HDL- cholesterol seems responsible for its efflux. The mechanism by which cholesterol is removed from extra-hepatic organs and delivered to the liver for its catabolism and excretion is called reverse cholesterol transport (RCT. Epidemiological evidence has associated high levels of HDL-cholesterol/ApoA-I with protection against atherosclerotic disease, but the ultimate mechanism(s responsible for the beneficial effect is not well established. HDLs are synthesized by the liver and small intestine and released to the circulation as a lipid-poor HDL (nascent HDL, mostly formed by ApoA-I and phospholipids. Through their metabolic maturation, HDLs interact with the ABCA1 receptor in the macrophage surface increasing their lipid content by taking phospholipids and cholesterol from macrophages becoming mature HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I, for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of RCT. It is clear that an inherited mutation or acquired abnormality in any of the key players in RCT mat affect the atherosclerotic process.

  20. RhoA and p38 MAPK mediate apoptosis induced by cellular cholesterol depletion.

    Science.gov (United States)

    Calleros, Laura; Lasa, Marina; Rodríguez-Alvarez, Francisco J; Toro, María J; Chiloeches, Antonio

    2006-07-01

    Cholesterol is essential for cell viability, and homeostasis of cellular cholesterol is crucial to various cell functions. Here we examined the effect of cholesterol depletion on apoptosis and the mechanisms underlying this effect in NIH3T3 cells. We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment resulted in a significant increase in cellular apoptosis and caspase-3 activation. This effect is not due to a deficiency of nonsterol isoprenoids, intermediate metabolites of the cholesterol biosynthetic pathway, but rather to low cholesterol levels, since addition of cholesterol together with LPDS and 25-HC nearly abolished apoptosis, whereas addition of farnesyl pyrophosphate or geranylgeranyl-pyrophosphate did not reverse the cell viability loss induced by LPDS plus 25-HC treatment. These effects were accompanied by an increase in ERK, JNK and p38 MAPK activity. However, only the inhibition of p38 MAPK with the specific inhibitor SB203580 or the overexpression of a kinase defective MKK6 resulted in a significant decrease in apoptosis and caspase-3 cleavage induced by cholesterol depletion. Furthermore, LPDS plus 25-HC increased RhoA activity, and this effect was reversed by addition of exogenous cholesterol. Finally, overexpression of the dominant negative N19RhoA inhibited p38 MAPK phosphorylation and apoptosis induced by low cholesterol levels. Together, our results demonstrate that cholesterol depletion induces apoptosis through a RhoA- and p38 MAPK-dependent mechanism.

  1. Cholesterol and benign prostate disease.

    Science.gov (United States)

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept.

  2. Steroidal Triterpenes of Cholesterol Synthesis

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    Damjana Rozman

    2013-04-01

    Full Text Available Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ24-reductase; DHCR24 the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (Vmax and Km and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols.

  3. EVALUATION OF SERUM CHOLESTEROL, AMINO TRANSFERASES

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    Anantha Babu

    2016-01-01

    Full Text Available BACKGROUND AND AIMS The purpose of this study was to determine the efficacy of red yeast rice (Monascus purpureus-fermented rice in lowering cholesterol in the blood. At the same time, alanine aminotranferase (ALT, aspartate aminotransferase (AST and gamma-glutamyl transferase (γ-GT were measured for notable side effects in the liver. Possible muscle damage was determined by measuring creatine kinase (CK. METHODS The cholesterol lowering effect in serum of red yeast rice-fed rats were studied over a 42-day feeding period. A total of 16 male Sprague-Dawley rats were randomised into 8 per group: control and treated. Treated rats were administered 1.35g/kg/day. Control rats were maintained on ordinary rat chow. RESULTS Serum cholesterol levels were significantly decreased by 19.13% in treated group compared to controls. This treatment also showed increase in serum ALT and AST activities by 41.90% and 21.53%, respectively. Mean CK activity in treated rats showed an increase by 32.32% when compared with control rats. γ-GT is the only enzyme that showed a decrease of 15.16% in sera of treated rats. Body weights of control and treated rats increased significantly by 10% end of feeding period but were not due to treatment. CONCLUSION Red yeast rice significantly decreased serum cholesterol level at a dosage of 1.35g/kg/day. However, the differences in serum enzyme activities between control and treated rats were not significant.

  4. LEVEL OF CHOLESTEROL AND FATTY ACIDS IN THE EGGS OF DIFFERENT SPECIES OF POULTRY. TEORES DE COLESTEROL E ÁCIDOS GRAXOS EM OVOS DE DIFERENTES ESPÉCIES DE AVES

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    T. T. OLIVEIRA

    2008-08-01

    Full Text Available This work had as objective to evaluate the cholesterol level fatty acids of triacylglicerol and phosphofolipids of eggs of the different poultry species. The following results were observed: cholesterol: goose duck> turkey > chicken > quail. Fatty acids of triacylglicerols: palmitic acid: turkey > quail goose > duck chicken. Estearic acid: quail chicken> goose duck perua. Oleic acid : goose > chicken> quail duck turkey. α-Linoleic acid: chicken> turkey quail > goose duck. Arachidonic acid: turkey > quail duck> chicken> goose. Docosahexanoic acid: turkey> duck goose chicken > quail. Phospholipids of fatty acids: palmí]itic acid: duck> goose quail > chicken turkey. Estearic acid: chicken turkey > quail> goose > duck. Oleic acid: duck goose > quail > turkey> chicken. α-Linoleic acid: turkey > chicken quail > duck goose. Arachidonic acid: duck > goose > quail chicken > turkey. Docosahexanoic acid: chicken> goose > turkey> quail duck. These results can be of importance for food tables and dietetic treatment of patients.

    Este trabalho teve como objetivo avaliar o teor de colesterol, ácidos graxos de triacilgliceróis e de fosfolipídeos de ovos de diferentes espécies de aves. Foram observados os seguintes resultados: As concentrações de colesterol foram maiores na: pata ≅ gansa > perua > galinha > codorna. As concentrações de ácidos graxos de triacilgliceróis: ácido palmítico: perua> gansa codorna > galinha >pata. Ácido esteárico: codorna galinha > gansa pata perua. Ácido oléico: gansa > galinha >codorna pata perua. Ácido -linoléico: galinha >codorna > perua > gansa pata. Ácido araquidônico: perua > codorna pata > galinha> gansa. Ácido docosaexanóico: perua > pata gansa galinha > codorna. Ácidos graxos de fosfolipídeos: ácido palmítico: pata > gansa codorna > galinha perua. Ácido esteárico: galinha

  5. Genetic therapies to lower cholesterol.

    Science.gov (United States)

    Khoo, Bernard

    2015-01-01

    This review surveys the state-of-the-art in genetic therapies for familial hypercholesterolaemia (FH), caused most commonly by mutations in the LDL receptor (LDLR) gene. FH manifests as highly elevated low density lipoprotein (LDL) cholesterol levels and consequently accelerated atherosclerosis. Modern pharmacological therapies for FH are insufficiently efficacious to prevent premature cardiovascular disease, can cause significant adverse effects and can be expensive. Genetic therapies for FH have been mooted since the mid 1990s but gene replacement strategies using viral vectors have so far been unsuccessful. Other strategies involve knocking down the expression of Apolipoprotein B100 (APOB100) and the protease PCSK9 which designates LDLR for degradation. The antisense oligonucleotide mipomersen, which knocks down APOB100, is currently marketed (with restrictions) in the USA, but is not approved in Europe due to its adverse effects. To address this problem, we have devised a novel therapeutic concept, APO-skip, which is based on modulation of APOB splicing, and which has the potential to deliver a cost-effective, efficacious and safe therapy for FH.

  6. Regulation of neuronal APL-1 expression by cholesterol starvation.

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    Mary Wiese

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP. While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD, sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1, and lrp-1 (lipoprotein receptor-related protein 1, suggesting a potential interaction between apl-1 and cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. CONCLUSIONS: Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

  7. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  8. HDL Cholesterol Efflux Capacity: Cardiovascular Risk Factor and Potential Therapeutic Target.

    Science.gov (United States)

    Bhatt, Anish; Rohatgi, Anand

    2016-01-01

    Low high-density lipoprotein cholesterol (HDL-C) levels are associated with incident cardiovascular events; however, many therapies targeting increases in HDL-C have failed to show consistent clinical benefit. Thus, focus has recently shifted toward measuring high-density lipoprotein (HDL) function. HDL is the key mediator of reverse cholesterol transport, the process of cholesterol extraction from foam cells, and eventual excretion into the biliary system. Cholesterol efflux from peripheral macrophages to HDL particles has been associated with atherosclerosis in both animals and humans. We review the mechanism of cholesterol efflux and the emerging evidence on the association between cholesterol efflux capacity and cardiovascular disease in human studies. We also focus on the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterol efflux.

  9. Trust Your Gut: Galvanizing Nutritional Interest in Intestinal Cholesterol Metabolism for Protection Against Cardiovascular Diseases

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    Jiyoung Lee

    2013-01-01

    Full Text Available Recent studies have demonstrated that the intestine is a key target organ for overall health and longevity. Complementing these studies is the discovery of the trans-intestinal cholesterol efflux pathway and the emerging role of the intestine in reverse cholesterol transport. The surfacing dynamics of the regulation of cholesterol metabolism in the intestine provides an attractive platform for intestine-specific nutritional intervention strategies to lower blood cholesterol levels for protection against cardiovascular diseases. Notably, there is mounting evidence that stimulation of pathways associated with calorie restriction may have a large effect on the regulation of cholesterol removal by the intestine. However, intestinal energy metabolism, specifically the idiosyncrasies surrounding intestinal responses to energy deprivation, is poorly understood. The goal of this paper is to review recent insights into cholesterol regulation by the intestine and to discuss the potential for positive regulation of intestine-driven cholesterol removal through the nutritional induction of pathways associated with calorie restriction.

  10. Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion

    Science.gov (United States)

    Tian, Yu; He, Lei; Shao, Yang; Li, Na

    2016-01-01

    Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD). The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA) against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD) supplement with perilla oil (POH) for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion. PMID:27642591

  11. Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion.

    Science.gov (United States)

    Chen, Ting; Yuan, Fahu; Wang, Hualin; Tian, Yu; He, Lei; Shao, Yang; Li, Na; Liu, Zhiguo

    2016-01-01

    Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD). The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA) against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD) supplement with perilla oil (POH) for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.

  12. New insights into the regulation of cholesterol efflux from the sperm membrane

    OpenAIRE

    Tamara Leahy; Bart M Gadella

    2015-01-01

    Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but t...

  13. Amperometric determination of serum total cholesterol with nanoparticles of cholesterol esterase and cholesterol oxidase.

    Science.gov (United States)

    Aggarwal, V; Malik, J; Prashant, A; Jaiwal, P K; Pundir, C S

    2016-05-01

    We describe the preparation of glutaraldehyde cross-linked and functionalized cholesterol esterase nanoparticles (ChENPs) and cholesterol oxidase nanoparticles (ChOxNPs) aggregates and their co-immobilization onto Au electrode for improved amperometric determination of serum total cholesterol. Transmission electron microscope (TEM) images of ChENPs and ChOxNPs showed their spherical shape and average size of 35.40 and 56.97 nm, respectively. Scanning electron microscope (SEM) studies of Au electrode confirmed the co-immobilization of enzyme nanoparticles (ENPs). The biosensor exhibited optimal response at pH 5.5 and 40°C within 5 s when polarized at +0.25 V versus Ag/AgCl. The working/linear range of the biosensor was 10-700 mg/dl for cholesterol. The sensor showed high sensitivity and measured total cholesterol as low as 0.1 mg/dl. The biosensor was evaluated and employed for total cholesterol determination in sera of apparently healthy and diseased persons. The analytical recovery of added cholesterol was 90%, whereas the within-batch and between-batch coefficients of variation (CVs) were less than 2% and less than 3%. There was a good correlation (r = 0.99) between serum cholesterol values as measured by the standard enzymic colorimetric method and the current method. The initial activity of ENPs/working electrode was reduced by 50% during its regular use (200 times) over a period of 60 days when stored dry at 4°C.

  14. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs.

    Science.gov (United States)

    Iqbal, Jahangir; Boutjdir, Mohamed; Rudel, Lawrence L; Hussain, M Mahmood

    2014-11-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production.

  15. Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance

    Science.gov (United States)

    Barrientos, G.; Sánchez-Aguilera, P.; Jaimovich, E.; Hidalgo, C.

    2017-01-01

    Membrane cholesterol is critical for signaling processes in a variety of tissues. We will address here current evidence supporting an emerging role of cholesterol on excitation-contraction coupling and glucose transport in skeletal muscle. We have centered our review on the transverse tubule system, a complex network of narrow plasma membrane invaginations that propagate membrane depolarization into the fiber interior and allow nutrient delivery into the fibers. We will discuss current evidence showing that transverse tubule membranes have remarkably high cholesterol levels and we will address how modifications of cholesterol content influence excitation-contraction coupling. In addition, we will discuss how membrane cholesterol levels affect glucose transport by modulating the insertion into the membrane of the main insulin-sensitive glucose transporter GLUT4. Finally, we will address how the increased membrane cholesterol levels displayed by obese animals, which also present insulin resistance, affect these two particular skeletal muscle functions. PMID:28367451

  16. Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.

    Science.gov (United States)

    Zheng, Wenchao; Mast, Natalia; Saadane, Aicha; Pikuleva, Irina A

    2015-01-01

    Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol- and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only upregulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance (apoD, Idol, and Rpe65) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.

  17. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

    Directory of Open Access Journals (Sweden)

    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  18. Dietary regulation of maternal and fetal cholesterol metabolism in the guinea pig.

    Science.gov (United States)

    Yount, N Y; McNamara, D J

    1991-08-20

    Studies to determine the effects of pre-natal interventions on maternal and fetal cholesterol homeostasis were carried out in the guinea pig. Guinea pig dams were fed either non-purified guinea pig diet or diet supplemented with either 1.1% of the bile acid binding resin cholestyramine or 0.25% cholesterol. Whole body rates of endogenous cholesterol synthesis were determined by quantitation of [3H]water incorporation into digitonin precipitable sterols in non-pregnant animals and at 40 and 60 days of gestation in the dam and fetus. Maternal hepatic cholesterol synthesis was reduced 87% by dietary cholesterol and was increased 3.5-fold with cholestyramine feeding. Fetal hepatic and peripheral tissue cholesterol synthesis rates peaked at 40 days gestation when peripheral tissue cholesterol synthesis was 5.7-fold higher and hepatic synthesis 6.2-fold greater than the near adult levels observed at 60 days. Cholesterol synthesis in the fetus was relatively insensitive to dietary manipulations; however, maternal cholestyramine treatment did result in a 1.4-fold increase in fetal carcass cholesterol synthesis at 60 days gestation. These data demonstrate that maternal cholesterogenic systems maintain responsiveness to dietary regulation during pregnancy; whereas fetal cholesterol homeostasis is relatively insensitive to dietary cholesterol throughout gestation yet may respond to induction by maternal cholestyramine treatment during the late gestation period.

  19. Substrate uptake and subcellular compartmentation of anoxic cholesterol catabolism in Sterolibacterium denitrificans.

    Science.gov (United States)

    Lin, Ching-Wen; Wang, Po-Hsiang; Ismail, Wael; Tsai, Yu-Wen; El Nayal, Ashraf; Yang, Chia-Ying; Yang, Fu-Chun; Wang, Chia-Hsiang; Chiang, Yin-Ru

    2015-01-09

    Cholesterol catabolism by actinobacteria has been extensively studied. In contrast, the uptake and catabolism of cholesterol by Gram-negative species are poorly understood. Here, we investigated microbial cholesterol catabolism at the subcellular level. (13)C metabolomic analysis revealed that anaerobically grown Sterolibacterium denitrificans, a β-proteobacterium, adopts an oxygenase-independent pathway to degrade cholesterol. S. denitrificans cells did not produce biosurfactants upon growth on cholesterol and exhibited high cell surface hydrophobicity. Moreover, S. denitrificans did not produce extracellular catabolic enzymes to transform cholesterol. Accordingly, S. denitrificans accessed cholesterol by direction adhesion. Cholesterol is imported through the outer membrane via a putative FadL-like transport system, which is induced by neutral sterols. The outer membrane steroid transporter is able to selectively import various C27 sterols into the periplasm. S. denitrificans spheroplasts exhibited a significantly higher efficiency in cholest-4-en-3-one-26-oic acid uptake than in cholesterol uptake. We separated S. denitrificans proteins into four fractions, namely the outer membrane, periplasm, inner membrane, and cytoplasm, and we observed the individual catabolic reactions within them. Our data indicated that, in the periplasm, various periplasmic and peripheral membrane enzymes transform cholesterol into cholest-4-en-3-one-26-oic acid. The C27 acidic steroid is then transported into the cytoplasm, in which side-chain degradation and the subsequent sterane cleavage occur. This study sheds light into microbial cholesterol metabolism under anoxic conditions.

  20. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  1. Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats.

    Science.gov (United States)

    Lapphanichayakool, Phakhamon; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip

    2017-01-01

    The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called "sericin-derived oligopeptides" (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg(-1) day(-1), 50 mg kg(-1) day(-1), and 200 mg kg(-1) day(-1)) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet. Triglyceride and HDL-cholesterol levels were not significantly changed among all groups. The fecal contents of bile acids and cholesterol did not differ among high-cholesterol fed rats. SDO dose-dependently reduced cholesterol solubility in lipid micelles, and inhibited cholesterol uptake in monolayer Caco-2 cells. SDO also effectively bound to all three types of bile salts including taurocholate, deoxytaurocholate, and glycodeoxycholate. Direct interaction with bile acids of SDO may disrupt micellar cholesterol solubility, and subsequently reduce the absorption of dietary cholesterol in intestines. Taking all data together, SDO or sericin peptides exhibit a beneficial effect on blood cholesterol levels and could be potentially used as a health-promoting dietary supplement or nutraceutical product.

  2. Cholesterol and triglycerides as biochemical markers of the state of the patient’s illness with acute lymphocytic leukemia

    OpenAIRE

    GUZMÁN, MARCO; Instituto de Enfermedades Neoplásicas; Sandoval, Miguel; Centro de Investigación de Bioquímica y Nutrición.

    2013-01-01

    Objective: To determine the relationship of cholesterol and triglycerides serum levels with the response to induction chemotherapy treatment in patients with acute lymphocytic leukemia. Material and Methods: The sample consisted in 25 patients 2 through 18 years-old admitted to the Neoplasia Diseases Institute with a recent diagnosis of acute lymphocytic leukemia in whom serum concentrations of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were determine, before and af...

  3. Study of Lipid Profile in Obese Individuals and the Effect of Cholesterol Lowering Agents on Them

    Directory of Open Access Journals (Sweden)

    Surajit Kumar Mukhopadhyay

    2012-04-01

    Full Text Available Objectives: To study the effect of cholesterol lowering agents on lipid profile in obese patients. Background: Obesity leads to morbidity as well as mortality. There is usually increased level of total cholesterol, LDL- cholesterol, VLDL- cholesterol, triglycerides and decreased level of HDL- cholesterol in obesity. These are the risk factors for cardiovascular disease, hypertension, diabetes mellitus, pulmonary disorder and gall stones. Method: Thirty obese patients received treatment with Lovastatin along with dietary measures, compared with age and sex matched controls- before and after 6 weeks of therapy, presented in a table and results were analysed using student's "t" test (both paired and unpaired. Result: There was significant reduction in total cholesterol as well as LDL- cholesterol; HDL- cholesterol was also increased significantly. But triglycerides and VLDL- cholesterol showed small but significant increase. Conclusion: Cholesterol lowering agents like Lovastatin was quite effective when used long-term in dyslipidaemia in obesity towards reduction of risk factors for cardiovascular diseases, strokes, etc. Hypertriglyceridaemia should also be treated adequately

  4. Polarizable multipolar electrostatics for cholesterol

    Science.gov (United States)

    Fletcher, Timothy L.; Popelier, Paul L. A.

    2016-08-01

    FFLUX is a novel force field under development for biomolecular modelling, and is based on topological atoms and the machine learning method kriging. Successful kriging models have been obtained for realistic electrostatics of amino acids, small peptides, and some carbohydrates but here, for the first time, we construct kriging models for a sizeable ligand of great importance, which is cholesterol. Cholesterol's mean total (internal) electrostatic energy prediction error amounts to 3.9 kJ mol-1, which pleasingly falls below the threshold of 1 kcal mol-1 often cited for accurate biomolecular modelling. We present a detailed analysis of the error distributions.

  5. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol tra

  6. Macrophage cholesterol homeostasis and metabolic diseases: critical role of cholesteryl ester mobilization.

    Science.gov (United States)

    Ghosh, Shobha

    2011-03-01

    Atherogenic dyslipidemia, including low HDL levels, is the major contributor of residual risk of cardiovascular disease that remains even after aggressive statin therapy to reduce LDL-cholesterol. Currently, distinction is not made between HDL-cholesterol and HDL, which is a lipoprotein consisting of several proteins and a core containing cholesteryl esters (CEs). The importance of assessing HDL functionality, specifically its role in facilitating cholesterol efflux from foam cells, is relevant to atherogenesis. Since HDLs can only remove unesterified cholesterol from macrophages while cholesterol is stored as CEs within foam cells, intracellular CE hydrolysis by CE hydrolase is vital. Reduction in macrophage lipid burden not only attenuates atherosclerosis but also reduces inflammation and linked pathologies such as Type 2 diabetes and chronic kidney disease. Targeting reduction in macrophage CE levels and focusing on enhancing cholesterol flux from peripheral tissues to liver for final elimination is proposed.

  7. Cholesterol absorption and excretion in ileostomy subjects on high- and low-dietary-cholesterol intakes.

    Science.gov (United States)

    Ellegård, L; Bosaeus, I

    1994-01-01

    Six healthy ileostomy subjects were given [3H]cholesterol and [14C]beta-sitosterol in a single meal together with two controlled diets containing 150 or 450 mg cholesterol/d. Each diet was eaten for 3 d. Cholesterol absorption and excretion of cholesterol, bile acids, fat, energy, and nitrogen were analyzed. Fractional cholesterol absorption increased from 44 +/- 2.6% (mean +/- SE) to 61 +/- 3.4% (P effluent, or excretion of energy, nitrogen, fat, and bile acids did not differ between periods. Endogenous cholesterol excretion remained unchanged whereas net cholesterol excretion (output minus intake) was 37% higher (P < 0.05) on low compared with high cholesterol intake.

  8. Amelioration of cholesterol induced atherosclerosis by normalizing gene expression, cholesterol profile and antioxidant enzymes by Vigna unguiculata.

    Science.gov (United States)

    Janeesh, P A; Abraham, Annie

    2013-06-01

    Cardiovascular diseases, especially atherosclerosis, have found to be the dreadful diseases worldwide and therapeutic interventions using plant sources have wide therapeutic value. Vigna unguiculata (VU) leaves have been used as food and therapeutics. Hence, our study was designed to evaluate the hypolipidemic as well as anti-atherogenic potential of VU leaves in normalizing atherogenic gene expression, cholesterol profile, generation of reactive oxygen species (ROS) and antioxidant enzyme system on cholesterol fed rabbit model. For the study New Zealand white rabbits were randomly divided into four groups of six animals each and experimental period was three months; group -i - ND [normal diet (40 g feed)], group-ii- ND (normal diet) +EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)], group -iii- ND [normal diet ]+ CFD [cholesterol fed diet (cholesterol 1 % of 40 g feed and cholic acid 0.5 % of 40 g feed)] and group-iv - ND [normal diet] +CFD [cholesterol fed diet ]+EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)]. Atherosclerosis was induced by feeding the rabbit with cholesterol (1 % of 40 g feed) and cholic acid (0.5 % of 40 g feed). Supplementation of EAVU normalized cholesterol profile, generation of reactive oxygen species (ROS), lipid peroxidation products like thiobarbituric acid reactive substance (TBARS), antioxidant system and important genes of cardiovascular diseases like interleukin-10 (IL 10), paraoxanase-1 (PON I), interleukin-6 (IL 6), and cyclooxygenase-2 (Cox 2) to near normal level as compared with normal diet. The result obtained showed the antioxidant as well as anti-atherogenic potential of Vigna unguiculata leaves in ameliorating cholesterol induced atherosclerosis, and thus it is good task to include VU leaves in daily diet for the prevention of cardiovascular diseases especially atherosclerosis.

  9. Awareness, Accuracy, and Predictive Validity of Self-reported Cholesterol in Women

    OpenAIRE

    Huang, Peng-yun A.; Buring, Julie Elizabeth; Paul M Ridker; Glynn, Robert J.

    2007-01-01

    Background: Although current guidelines emphasize the importance of cholesterol knowledge, little is known about accuracy of this knowledge, factors affecting accuracy, and the relationship of self-reported cholesterol with cardiovascular disease (CVD). Methods: The 39,876 female health professionals with no prior CVD in the Women’s Health Study were asked to provide self-reported and measured levels of total and high-density lipoprotein (HDL) cholesterol. Demographic and cardiovascular risk ...

  10. Iatrogenic severe depression of high-density lipoprotein cholesterol.

    Science.gov (United States)

    Mymin, D; Dembinski, T; Friesen, M H

    2009-07-01

    The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

  11. Arterial elasticity in population with different levels of low density lipoprotein cholesterol%不同水平的低密度脂蛋白胆固醇人群的动脉弹性

    Institute of Scientific and Technical Information of China (English)

    陶红; 林江; 陈立新; 岑敏

    2010-01-01

    Objective To investigate the arterial elasticity change in population with different levels of low density l ipoprotein cholesterol (LDL-C). Methods A total of 315 persons, 175 males and 140 females, aged (51 ± 11 ) years old, who underwent physical examination in our hospital during January 2008 and December 2009, were classified into 4 groups according to the national cholesterol education program Ⅲ criteria: normal LDL-C group (C group, n=88, LDL-C: 2.63-3.41 mmol/L); supercritical LDL-C group (H1 group, n=37, LDL-C: 3.42-4.20 mmol/L); high LDL-C group (H2 group, n=69, LDL-C: 4.21-4.97 mmol/L);severe high LDL-C group (H3 group, n= 121, LDL-C ≥4.98 mmol/L). Pulse wave velocity (PWV) and Anklebrachial index (ABI) were measured by arteriosclerosis measurement system to evaluate the elasticity. The difference in 4 groups was compared. Results PWV values in H2 and H3 groups were mildly elevated, with statistical difference compared with C and H1 groups whose PWV values were within normal range [H2 group:( 1623± 115) cm/s, H3 group: ( 1720± 100) cm/s, C group: ( 1288± 103) cm/s, H 1 group: ( 1266± 112) cm/s,P<0.05]. ABI in all the groups was normal with no significant differences. Conclusion Early increased LDL- C may lead to mild reduction of artery elasticity. PWV may be helpful to detect early artery atherosclerosis.%目的 观察不同水平的低密度脂蛋白胆固醇(LDL-C)人群动脉弹性的变化.方法 对象为2008年1月至2009年12月在本院体检中心体检者315例,平均年龄(51±11)岁,男性175例,女性140例.根据美国国家胆固醇教育计划(NCEP-Ⅲ)标准,按照血清LDL-C水平分为4组:LDL-C正常组(C组,n=88,LDL-C:2.63~3.41 mmol/L);LDL-C临界升高组(H1组,n=37,LDL-C:3.42~4.20mmol/L);LDL-C升高组(H2组,n=69,LDL-C:4.21~4.97mmol/L);LDL-C显著升高组(H3组,n=121,LDL-C≥4.98 mmol/L).应用动脉硬化测定仪检测各组体检者的脉搏波传导速度(PWV)和踝臂指数(ABI),并行组间比较.结果 C

  12. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten

    2004-01-01

    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  13. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  14. Domain 4 (D4 of Perfringolysin O to Visualize Cholesterol in Cellular Membranes—The Update

    Directory of Open Access Journals (Sweden)

    Masashi Maekawa

    2017-03-01

    Full Text Available The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine. Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4 of Perfringolysin O (PFO, theta toxin, a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

  15. Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

    Science.gov (United States)

    Alonso, L; Fontecha, J; Cuesta, P

    2016-01-14

    A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (Pacidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations.

  16. Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes—The Update

    Science.gov (United States)

    Maekawa, Masashi

    2017-01-01

    The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking) in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine). Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4) of Perfringolysin O (PFO, theta toxin), a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes. PMID:28273804

  17. Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

    Directory of Open Access Journals (Sweden)

    Su-Myat Khine K

    2010-06-01

    Full Text Available Abstract Background Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD, Alzheimer's disease (AD, and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer. Results Using plasmalogen deficient (NRel-4 and plasmalogen sufficient (HEK293 cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA-containing ethanolamine plasmalogen (PlsEtn present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1 levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA reductase inhibition. Conclusion The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells.

  18. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  19. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  20. Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

    Institute of Scientific and Technical Information of China (English)

    Katriina; Nemes; Fredrik; ?berg; Helena; Gylling; Helena; Isoniemi

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

  1. What You Need to Know about Cholesterol

    Science.gov (United States)

    ... 164304.html What You Need to Know About Cholesterol Heart expert explains the difference between good and ... 28, 2017 MONDAY, March 27, 2017 (HealthDay News) -- Cholesterol plays a vital role in your health, so ...

  2. High Cholesterol: Medicines to Help You

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women High Cholesterol--Medicines To Help You Share Tweet Linkedin Pin ... side effects for each drug, check Drugs@FDA . Cholesterol Absorption Inhibitors Brand Name Generic Name Zetia Ezetimibe ...

  3. Active membrane cholesterol as a physiological effector.

    Science.gov (United States)

    Lange, Yvonne; Steck, Theodore L

    2016-09-01

    Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily.

  4. Cholesterol, bile acid and triglyceride metabolism intertwined

    NARCIS (Netherlands)

    Schonewille, Marleen

    2016-01-01

    Hyperlipidemie wordt gekarakteriseerd door verhoogd plasma cholesterol en/of triglyceriden en sterk geassocieerd met het risico op cardiovasculaire aandoeningen. Dit proefschrift beschrijft onderzoek naar de regulatie van plasma cholesterol en triglyceriden concentraties en de achterliggende mechani

  5. Cholesterol metabolism and homeostasis in the brain

    OpenAIRE

    Zhang, Juan; Qiang LIU

    2015-01-01

    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer’s disease (AD), Huntington’s disease (HD)...

  6. Effect of Taurine on Cholesterol Level of HepG2 Cells%牛磺酸对HepG2细胞胆固醇水平的影响

    Institute of Scientific and Technical Information of China (English)

    张珊; 郭俊霞; 张艳贞; 张静; 陈文

    2014-01-01

    目的:探讨牛磺酸对人肝癌细胞HepG2总胆固醇(total cholesterol,TC)、游离胆固醇(free cholesterol,FC)、胆固醇酯(cholesterol ester,EC)水平及对胆固醇代谢限速酶——胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)蛋白表达的影响.方法:在培养液中添加终浓度为0.1、1、10、20 mmol/L的牛磺酸,分别在培养24、48 h后测定细胞内TC、FC及EC水平;在培养液中添加终浓度为20 mmol/L的牛磺酸,分别培养12、24、48、72 h后检测CYP7A1蛋白表达水平.结果:1、10、20 mmol/L的牛磺酸均可使HepG2细胞内TC、FC水平明显下降,且与牛磺酸浓度呈正比,但EC水平在牛磺酸浓度达1 mmol/L后即不随牛磺酸浓度的增加而进一步降低;培养48 h后HepG2细胞TC、FC水平的降低幅度大于24 h时;20 mmol/L牛磺酸使FC含量减少的作用强于对EC减少的作用;培养24 h后HepG2细胞中CYP7A1蛋白表达最强.结论:牛磺酸可增强CYP7A1蛋白表达,促进HepG2细胞内的胆固醇代谢,胆固醇降低程度与牛磺酸浓度及作用时间相关,作用48 h的效果明显优于24 h,且牛磺酸主要是降低了细胞内的FC水平.

  7. Analysis of ABCA1 and cholesterol efflux in HIV-infected cells

    Science.gov (United States)

    Mukhamedova, Nigora; Brichacek, Beda; Darwish, Christina; Popratiloff, Anastas; Sviridov, Dmitri; Bukrinsky, Michael

    2016-01-01

    Summary Cholesterol is an essential component of the cellular membranes and, by extension, of the HIV envelope membrane, which is derived from the host cell plasma membrane. Depletion of the cellular cholesterol has a inhibitory effect on HIV assembly, reduces infectivity of the produced virions, and makes the cell less susceptible to HIV infection. It is not surprising that the virus has evolved to gain access to cellular proteins regulating cholesterol metabolism. One of the key mechanisms used by HIV to maintain high levels of cholesterol in infected cells is Nef-mediated inhibition of cholesterol efflux and the cholesterol transporter responsible for this process, ABCA1. In this article, we describe methods to investigate these effects of HIV-1 infection. PMID:26714719

  8. Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Rampratap S. Kushwaha

    2004-01-01

    Full Text Available The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL + LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL + LDL cholesterol concentrations (30%–60% and an increase in HDL cholesterol concentrations (10%–20%. VLDL + LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL + LDL cholesterol (20%–60% and an increase in HDL cholesterol (10%–20%. VLDL + LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

  9. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  10. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  11. Cholesterol Screening: A Practical Guide to Implementation.

    Science.gov (United States)

    Kingery, Paul M.

    1995-01-01

    Dry-chemistry cholesterol analysis has made screening feasible in a variety of settings. The article provides practical tips for the implementation of mass cholesterol screening using a portable dry-chemistry analyzer and discusses issues involved in conducting effective cholesterol screening programs from start to finish. (SM)

  12. Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit’s Nictitating Membrane Response

    Directory of Open Access Journals (Sweden)

    Bernard G. Schreurs

    2012-01-01

    Full Text Available A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit’s nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory.

  13. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  14. Cholesterol Metabolism and Prostate Cancer Lethality.

    Science.gov (United States)

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

  15. D38-cholesterol as a Raman active probe for imaging intracellular cholesterol storage

    Science.gov (United States)

    Alfonso-García, Alba; Pfisterer, Simon G.; Riezman, Howard; Ikonen, Elina; Potma, Eric O.

    2016-06-01

    We generated a highly deuterated cholesterol analog (D38-cholesterol) and demonstrated its use for selective vibrational imaging of cholesterol storage in mammalian cells. D38-cholesterol produces detectable signals in stimulated Raman scattering (SRS) imaging, is rapidly taken up by cells, and is efficiently metabolized by acyl-CoA cholesterol acyltransferase to form cholesteryl esters. Using hyperspectral SRS imaging of D38-cholesterol, we visualized cholesterol storage in lipid droplets. We found that some lipid droplets accumulated preferentially unesterified D38-cholesterol, whereas others stored D38-cholesteryl esters. In steroidogenic cells, D38-cholesteryl esters and triacylglycerols were partitioned into distinct sets of lipid droplets. Thus, hyperspectral SRS imaging of D38-cholesterol demonstrates a heterogeneous incorporation of neutral lipid species, i.e., free cholesterol, cholesteryl esters, and triacylglycerols, between individual lipid droplets in a cell.

  16. Dietary cholesterol and plasma lipoprotein profiles: Randomized controlled trials

    Science.gov (United States)

    Early work suggested that dietary cholesterol increased plasma total cholesterol concentrations in humans. Given the relationship between elevated plasma cholesterol concentrations and cardiovascular disease risk, dietary guidelines have consistently recommended limiting food sources of cholesterol....

  17. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol originat

  18. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Boesjes, Marije; Wolters, Henk; Bloks, Vincent W; Bos, Trijnie; van Dijk, Theo H; Jurdzinski, Angelika; Boverhof, Renze; Wolters, Justina C; Kuivenhoven, Jan A; van Deursen, Jan M; Oude Elferink, Ronald P J; Moschetta, Antonio; Kremoser, Claus; Verkade, Henkjan J; Kuipers, Folkert; Groen, Albert K

    2017-01-01

    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) cont

  19. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy...... and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly....

  20. The ABCG5/8 Cholesterol Transporter and Myocardial Infarction Versus Gallstone Disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVES: The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone...... disease in opposite directions. BACKGROUND: High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI...... and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5...

  1. Peptide mediators of cholesterol efflux

    Science.gov (United States)

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  2. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We perform...

  3. A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

    Institute of Scientific and Technical Information of China (English)

    SUNJing; ZHANGAi-xia; LUOChun-xia; WANGWei; SUNYong-jun; ZHUDong-ya

    2004-01-01

    To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis. Sermn NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol. The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Resu/ts.Cholesterol diet significantly increased sermn levels of cholesterol and LDL, caused a remarkable platelet hyperaggregability, and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination. The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNIP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclexosis. :The present study suggests that the endothelial dysfunction caused by enhanced sermn cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.

  4. Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias.

    Science.gov (United States)

    Roever, Leonardo

    2016-05-01

    Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.

  5. Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model

    Science.gov (United States)

    Cholestyramine(CA)is a bile acid sequestrant widely used as a cholesterol-lowering drug to treat hypercholesterolemia, one of the major risk factors for cardiovascular disease. Despite the wide use of CA its effect on cholesterol and lipid metabolism at a molecular level and over the long term remai...

  6. Intracellular transport of cholesterol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of ({sup 3}H)cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth.

  7. Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

    Science.gov (United States)

    Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

    1997-06-01

    Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

  8. Cholesterol metabolism and homeostasis in the brain.

    Science.gov (United States)

    Zhang, Juan; Liu, Qiang

    2015-04-01

    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

  9. Air Force Members’ Guide for Reducing Cholesterol Ratio,

    Science.gov (United States)

    1987-04-01

    two factors you cannot control, but should be aware of, are diabetes and heredity. The following guide tells you how to positively affect the...0.4 Buttermilk (1% fat) 2.2 Nonfat dry milk powder(l/4 cup) 0.2 Condensed, sweetened 26.6 Evaporated milk, whole 19.1 Evaporated milk, skim 0.5...cholesterol ratio. Diabetes Diabetes can Increase the risk of heart disease. A diabetic tends to have above normal levels of blood cholesterol 12 .~~tr~~rr

  10. Cholesterol and Alzheimer Type Dementia among Adults with Down Syndrome

    Science.gov (United States)

    Buckley, Frank

    2008-01-01

    This article reports a summary of research by Warren Zigman and colleagues investigating the link between cholesterol levels and Alzheimer type dementia among adults with Down syndrome. Warren Zigman and colleagues followed 123 adults with Down syndrome between May 1998 and April 2006. The participants were aged between 41 and 78 years at the…

  11. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  12. Dietary cholesterol supplementation to a plant-based diet suppresses the complete pathway of cholesterol synthesis and induces bile acid production in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Kortner, Trond M; Björkhem, Ingemar; Krasnov, Aleksei; Timmerhaus, Gerrit; Krogdahl, Åshild

    2014-06-28

    Plants now supply more than 50 % of protein in Norwegian salmon aquafeeds. The inclusion of plant protein in aquafeeds may be associated with decreased lipid digestibility and cholesterol and bile salt levels, indicating that the replacement of fishmeal with plant protein could result in inadequate supplies of cholesterol in fish. A reduction in feed efficiency, fish growth and pathogen resistance is often observed in parallel to alterations in sterol metabolism. Previous studies have indicated that the negative effects induced by plant components can be attenuated when diets are supplemented with cholesterol. The present study evaluated the effects of dietary cholesterol supplementation (1·5 %) in Atlantic salmon fed a plant-based diet for 77 d. The weights of body, intestines and liver were recorded and blood, tissues, faeces, chyme and bile were sampled for the evaluation of effects on growth, nutrient utilisation and metabolism, and transcriptome and metabolite levels, with particular emphasis on sterol metabolism and organ structure and function. Cholesterol supplementation did not affect the growth or organ weights of Atlantic salmon, but seemed to promote the induction of cholesterol and plant sterol efflux in the intestine while suppressing sterol uptake. Cholesterol biosynthesis decreased correspondingly and conversion into bile acids increased. The marked effect of cholesterol supplementation on bile acid synthesis suggests that dietary cholesterol can be used to increase bile acid synthesis in fish. The present study clearly demonstrated how Atlantic salmon adjusted their metabolic functions in response to the dietary load of cholesterol. It has also expanded our understanding of sterol metabolism and turnover, adding to the existing, rather sparse, knowledge of these processes in fish.

  13. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  14. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    Science.gov (United States)

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-02

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.

  15. Conversion of Exogenous Cholesterol into Glycoalkaloids in Potato Shoots, Using Two Methods for Sterol Solubilisation

    Science.gov (United States)

    Petersson, Erik V.; Nahar, Nurun; Dahlin, Paul; Broberg, Anders; Tröger, Rikard; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

    2013-01-01

    Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D) in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled), and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine) were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato. PMID:24349406

  16. Conversion of exogenous cholesterol into glycoalkaloids in potato shoots, using two methods for sterol solubilisation.

    Directory of Open Access Journals (Sweden)

    Erik V Petersson

    Full Text Available Steroidal glycoalkaloids (SGA are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D in the sterol ring structure (D5- or D6-labelled, or side chain (D7-labelled, and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato.

  17. Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain.

    Science.gov (United States)

    Saeed, Ahmed A; Genové, Guillem; Li, Tian; Lütjohann, Dieter; Olin, Maria; Mast, Natalia; Pikuleva, Irina A; Crick, Peter; Wang, Yuqin; Griffiths, William; Betsholtz, Christer; Björkhem, Ingemar

    2014-08-22

    The presence of the blood-brain barrier (BBB) is critical for cholesterol metabolism in the brain, preventing uptake of lipoprotein-bound cholesterol from the circulation. The metabolic consequences of a leaking BBB for cholesterol metabolism have not been studied previously. Here we used a pericyte-deficient mouse model, Pdgfb(ret/ret), shown to have increased permeability of the BBB to a range of low-molecular mass and high-molecular mass tracers. There was a significant accumulation of plant sterols in the brains of the Pdgfb(ret/ret) mice. By dietary treatment with 0.3% deuterium-labeled cholesterol, we could demonstrate a significant flux of cholesterol from the circulation into the brains of the mutant mice roughly corresponding to about half of the measured turnover of cholesterol in the brain. We expected the cholesterol flux into the brain to cause a down-regulation of cholesterol synthesis. Instead, cholesterol synthesis was increased by about 60%. The levels of 24(S)-hydroxycholesterol (24S-OHC) were significantly reduced in the brains of the pericyte-deficient mice but increased in the circulation. After treatment with 1% cholesterol in diet, the difference in cholesterol synthesis between mutants and controls disappeared. The findings are consistent with increased leakage of 24S-OHC from the brain into the circulation in the pericyte-deficient mice. This oxysterol is an efficient suppressor of cholesterol synthesis, and the results are consistent with a regulatory role of 24S-OHC in the brain. To our knowledge, this is the first demonstration that a defective BBB may lead to increased flux of a lipophilic compound out from the brain. The relevance of the findings for the human situation is discussed.

  18. Nitric oxide-mediated endothlium-dependent vasodilation is impaired with borderline high-LDL cholesterol.

    Science.gov (United States)

    Diehl, Kyle J; Stauffer, Brian L; Greiner, Jared J; Weil, Brian R; DeSouza, Christopher A

    2012-02-01

    The experimental aims of this study were to determine: (1) whether nitric oxide-mediated endothelium-dependent vasodilation is blunted in adult humans with borderline high plasma low-density lipoprotein (LDL)-cholesterol compared with adults with optimal/near optimal LDL-cholesterol levels; and, if so: (2) whether the magnitude of impairment in adults with borderline high LDL-cholesterol is similar to adults with high LDL-cholesterol. Forearm blood flow responses to intraarterial infusions of acetylcholine and sodium nitroprusside were measured in 50 middle-aged (43-64 year) adults: 20 in the optimal/near optimal LDL-cholesterol range (<130 mg/dL); 20 with borderline high LDL-cholesterol (130-159 mg/dL); and 10 with high LDL-cholesterol ($160 mg/dL). In addition, blood flow responses to acetylcholine were determined in the absence and presence of the endothelial nitric oxide synthase inhibitor N(G) -monomethyl-L-arginine (L-NMMA). Vasodilation to acetylcholine was ~20% lower (p < 0.05) in the borderline high (from 4.3 ± 0.2 to 12.3 ± 0.8 mL/100 mL tissue/min) and high (from 4.3 ± 0.3 to 12.0 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol groups compared with the optimal/near optimal (from 4.4 ± 0.2 to 14.5 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol group. L-NMMA significantly reduced (~30%) the vasodilator response to acetylcholine in the optimal/near optimal LDL-cholesterol group but not the borderline high or high LDL-cholesterol groups. Borderline high LDL-cholesterol is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

  19. Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse.

    Science.gov (United States)

    Yue, Hai-Yuan; Xu, Jianhua

    2015-07-01

    Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from non-specific effects after cholesterol manipulation. Furthermore, it remains unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase or methyl-β-cyclodextrin impaired three different forms of endocytosis, including slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca(2+) channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of methyl-β-cyclodextrin reduced exocytosis, mainly by decreasing the readily releasable pool and the vesicle replenishment after readily releasable pool depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses.

  20. Emotional eating as a mediator between anxiety and cholesterol in population with overweight and hypertension.

    Science.gov (United States)

    Mensorio, Marinna S; Cebolla, Ausiàs; Lisón, Juan Francisco; Rodilla, Enrique; Palomar, Gonzalo; Miragall, Marta; Baños, Rosa Maria

    2016-12-23

    Although the relationship between cholesterol and mood states (especially anxiety) has been well studied, few researches have included the role of eating styles in this relationship. This study explored the associations among eating styles, negative emotional symptoms, and levels of cholesterol (and other medical variables) in a population with hypertension and overweight or obesity, analyzing the possible mediation mechanisms involved. A cross-sectional study was conducted in 68 adults with hypertension and overweight/obesity, and stepwise multiple regression analysis and mediation analyses were carried out to test the hypothesis that eating styles mediate the relationship between negative emotional symptoms and cholesterol. Several significant correlations among age, anthropometric, medical, and psychological variables (eating styles and negative emotional symptoms) were found. There was a significant indirect effect of anxiety on total cholesterol and LDL cholesterol through emotional eating. Results suggest that emotional eating has a relevant role in the rise in total and LDL cholesterol, acting as a mediator in the relationship between anxiety and cholesterol. This finding could have important implications, since it introduces a new variable in the relationship between emotions and cholesterol and, therefore, changes the way of understanding this relationship, and of treating high cholesterol in a hypertensive sample.

  1. The mechanism of lowering cholesterol absorption by calcium studied by using an in vitro digestion model.

    Science.gov (United States)

    Vinarova, Liliya; Vinarov, Zahari; Tcholakova, Slavka; Denkov, Nikolai D; Stoyanov, Simeon; Lips, Alex

    2016-01-01

    Studies in humans show that a calcium-enriched diet leads to lower cholesterol in blood serum. This phenomenon is usually explained in the literature with a reduced cholesterol absorption in the small intestine. Our study aims to clarify the effect of calcium on the solubilisation of cholesterol and fatty acid in the dietary mixed micelles (DMM), viz. on the bioaccessibility of these lipophilic substances in the gut. We use an in vitro digestion model which mimics very closely the intestinal pH-profile and the composition of the intestinal fluids. We quantified the effects of Ca(2+) concentration on the lipid solubilization for fats and oils with different saturated/unsaturated fatty acid (FA) contents. We found that the increase of calcium significantly decreases the solubilization of cholesterol, FA and MG. Most importantly, we observe a clear positive correlation between the amounts of solubilized cholesterol, on one side, and solubilized free fatty acids and monoglycerides, on the other side. The main conclusion is that Ca(2+) ions strongly affect the bioaccessibility of both cholesterol and saturated FA. Therefore, calcium may decrease the serum cholesterol via two complementary mechanisms: (1) fatty acid precipitation by calcium ions reduces the solubilisation capacity of the DMM, thus decreasing the levels of solubilised (bioaccessible) cholesterol; (2) the observed strong decrease of the bioaccessible saturated FA, in its own turn, may suppress the cholesterol synthesis in the liver.

  2. Physiological performance of quails that underwent dietary and pharmacological manipulation of cholesterol.

    Science.gov (United States)

    Botelho, G G; Falbo, M K; Ost, P R; Czekoski, Z M; Raviolo, A E; Giotto, F M; Goldoni, E C; Morais, R N

    2015-06-01

    The present work evaluated whether dietary and pharmacological interference on cholesterol synthesis were capable of inducing alterations in blood and yolk cholesterol levels and the secretion of corticosterone metabolites. Forty-five 40-day-old quails were divided into three experimental groups: vegetal fat diet, 2% beef fat (tallow) diet and vegetal fat diet with simvastatin administration (3.13 mg/kg/day). During all experiments, the animal weights and food consumption were recorded and blood and faecal samples (days 0, 15, 30, 45 and 60), as well as eggs (days 30, 45 and 60), were collected. Analysis of serum and yolk cholesterol was performed and faecal corticosterone levels were measured. No differences were observed on blood cholesterol or faecal corticosterone between all treatments, despite a tendency of increased cholesterol in the group with the animal fat diet. However, quails submitted to an animal fat diet displayed an increase in yolk cholesterol at day 30 of the treatment and the egg yolks of quails treated with simvastatin exhibited a decrease in cholesterol content by the end of the treatment at 60 days. These results improved the knowledge regarding the physiology of quails and offered support to other studies concerning the consequences of the pharmacological treatment and the dietary manipulation of cholesterol levels.

  3. Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries

    Directory of Open Access Journals (Sweden)

    Meritxell Reverter

    2014-05-01

    Full Text Available Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN. Here, using Chinese hamster ovary (CHO Niemann-Pick type C1 (NPC1 mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6 accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs. This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

  4. Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Frikke-Schmidt, Ruth

    2015-01-01

    AIMS: Ezetimibe reduces plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting Niemann-Pick C1-Like protein 1 (NPC1L1), the transporter responsible for cholesterol uptake from the intestine into enterocytes and from the bile into hepatocytes. We tested the hypothesis that genetic...... developed IVD or symptomatic gallstone disease, respectively, during follow-up from 1977 to 2013. We genotyped four common NPC1L1 variants, previously associated with reduced LDL cholesterol levels, thus mimicking the effect of ezetimibe, and calculated a weighted genotype score. With increasing genotype...... score, LDL cholesterol decreased stepwise up to 3.5% (0.12 mmol/L) and total cholesterol up to 1.9% (0.11 mmol/L) (P-trend: 2 × 10(-12) and 2 × 10(-9)). The cumulative incidence by age of IVD decreased, while that of symptomatic gallstone disease increased as a function of increasing genotype score (P...

  5. Cholesterol deregulation induced by chronic corticosterone (CORT) stress in pectoralis major of broiler chickens.

    Science.gov (United States)

    Duan, Yujing; Fu, Wenyan; Wang, Song; Ni, Yingdong; Zhao, Ruqian

    2014-10-01

    Chronic endogenous glucocorticoid (GC) excess in mammals is associated with metabolic dysfunction and dyslipidemia that are characterized by increased plasma triglyceride and total cholesterol (Tch) levels. However, the effects of chronic GC administration on cholesterol metabolism, particularly in muscle tissues of broiler chickens, are unknown. In this study, broiler chickens were treated chronically with vehicle (CON) or corticosterone (CORT) for 2 weeks. Chronic CORT treatment significantly increased Tch levels in pectoralis major muscle (PMC) (p0.05). Western blot results showed that the levels of total GR (p=0.08) tended to be increased and nuclear GR protein (pchickens by increasing cholesterol synthesis and uptake.

  6. Improved Coarse-Grained Modeling of Cholesterol-Containing Lipid Bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Daily, Michael D.; Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.; Baker, Nathan A.

    2014-03-24

    In mammalian cells cholesterol is essential for membrane function, but in excess can be cytototoxic. The cellular response to acute cholesterol loading involves biophysical-based mechanisms that regulate cholesterol levels, through modulation of the “activity” or accessibility of cholesterol to extra-membrane acceptors. Experiments and united atom (UA) simulations show that at high concentrations of cholesterol, lipid bilayers thin significantly and cholesterol availability to external acceptors increases substantially. Such cholesterol activation is critical to its trafficking within cells. Here we aim to reduce the computational cost to enable simulation of large and complex systems involved in cholesterol regulation, such as those including oxysterols and cholesterol-sensing proteins. To accomplish this, we have modified the published MARTINI coarse-grained force field to improve its predictions of cholesterol-induced changes in both macroscopic and microscopic properties of membranes. Most notably, MARTINI fails to capture both the (macroscopic) area condensation and membrane thickening seen at less than 30% cholesterol and the thinning seen above 40% cholesterol. The thinning at high concentration is critical to cholesterol activation. Microscopic properties of interest include cholesterol-cholesterol radial distribution functions (RDFs), tilt angle, and accessible surface area. First, we develop an “angle-corrected” model wherein we modify the coarse-grained bond angle potentials based on atomistic simulations. This modification significantly improves prediction of macroscopic properties, most notably the thickening/thinning behavior, and also slightly improves microscopic property prediction relative to MARTINI. Second, we add to the angle correction a “volume correction” by also adjusting phospholipid bond lengths to achieve a more accurate volume per molecule. The angle + volume correction substantially further improves the quantitative

  7. Colesterol e composição dos ácidos graxos nas dietas para humanos e na carcaça suína Fatty acids concentration and level of cholesterol in diets for humans and present in swine carcasses

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Mohaupt Marques Ludke

    1999-03-01

    Full Text Available O colesterol é uma substância complexa do tipo lipídio-esteróide presente principalmente nas gorduras animais. Apresenta múltiplas funções no organismo, entretanto, problemas no metabolismo do colesterol no organismo podem acarretar aumento na sua concentração no sangue e conseqüentemente doenças coronárias como arterosclerose. Porém, já está comprovado que o consumo de colesterol é um fator de risco para pessoas que apresentam problemas genéticos de regulação do seu metabolismo. São pessoas que possuem níveis de colesterol acima de 200mg/dl e com concentração de HDL no sangue inferior a 35mg/dl. Apenas para estes indivíduos é importante o controle do colesterol através da dieta, na qual o consumo de carne suína, como de qualquer carne de outra espécie animal, deve ser considerada a composição dos ácidos graxos da gordura subcutânea e intramuscular. O fornecimento de dietas para suínos com maior concentração de ácidos graxos poliinsaturados apresentaram maior teor deste tipo de gordura nas suas carcaças. A suplementação destas gorduras de origem vegetal não pode ultrapassar a 4% nas dietas, devido à obtenção de carcaças com deficiência de conservação, apesar de originar uma carne mais benéfica à saúde do consumidor.Cholesterol is a complex lipid-steroid like substance mostly present in animal fat, and it has many essencial functions in living organisms. However, in humans, any metabolic problems can increase blood cholesterol concentration and, consequently, increase the risk of coronary heart disease, such as arteriosclerosis. It is a known fact that cholesterol consumption is a risk factor for people who have genetic disorders in the metabolic regulation of cholesterol. These people have plasma levels of cholesterol above 200mg/dl and a plasma concentration of high density lipoprotein (HDL under 35mg/dl. For these people, it is important to control the cholesterol level in the diet. The

  8. Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tao; WU Wen-feng; LIU Yang; WANG Qi-hui; WANG Lü-ya; MI Shu-hua

    2013-01-01

    Background Statins and ezetimibe have been reported to change the balance of cholesterol metabolism,but few studies have been performed on Chinese patients.The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.Methods Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks.Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level.Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week.The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st,4th,and 12th week of the study by gas chromatography.Results After treatment with simvastatin for four weeks,the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P <0.05).On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P <0.001) compared to levels during the 4th week.By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P<0.05) compared with levels measured during the 4th week.Conclusions Coronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment.Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

  9. 2-Heptyl-Formononetin Increases Cholesterol and Induces Hepatic Steatosis in Mice

    Directory of Open Access Journals (Sweden)

    Charlotte Andersen

    2013-01-01

    Full Text Available Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F, on lipid and cholesterol metabolism in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma level of total cholesterol. Supplementation with formononetin did not affect plasma cholesterol but increased plasma triglycerides levels. Supplementation with formononetin and C7F induced hepatic steatosis. However, formononetin decreased markers of inflammation and liver injury. The development of hepatic steatosis was associated with deregulated expression of hepatic genes involved in lipid and lipoprotein metabolism. In conclusion, supplementation with formononetin and C7F to a cholesterol-enriched diet adversely affected lipid and lipoprotein metabolism in C57BL/6J mice.

  10. New insights into the regulation of cholesterol efflux from the sperm membrane.

    Science.gov (United States)

    Leahy, Tamara; Gadella, Bart M

    2015-01-01

    Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon's preparation for fertilization. Some factors that regulate these events are described (e.g., bicarbonate, calcium) but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings? This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledge, sperm handling techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.

  11. Effects of apple cider vinegars produced with different techniques on blood lipids in high-cholesterol-fed rats.

    Science.gov (United States)

    Budak, Nilgun H; Kumbul Doguc, Duygu; Savas, Cagri M; Seydim, Atif C; Kok Tas, Tugba; Ciris, Metin I; Guzel-Seydim, Zeynep B

    2011-06-22

    Red delicious apples were used to produce natural apple cider with and without inclusion of maceration. Traditional surface and industrial submersion methods were then applied to make vinegar from apple ciders. Apple cider vinegar samples produced with inclusion of maceration in the surface method had the highest total phenolic content, chlorogenic acid, ORAC, and TEAC levels. Cholesterol and apple vinegar samples were administered using oral gavage to all groups of rats except the control group. Apple cider vinegars, regardless of the production method, decreased triglyceride and VLDL levels in all groups when compared to animals on high-cholesterol diets without vinegar supplementation. Apple cider vinegars increased total cholesterol and HDL and LDL cholesterol levels and decreased liver function tests when compared to animals on a high-cholesterol diet without vinegar supplementation. A high-cholesterol diet resulted in hepatic steatosis. VSBM and VSB groups significantly decreased steatosis.

  12. Biophysical studies of cholesterol effects on chromatin.

    Science.gov (United States)

    Silva, Isabel T G; Fernandes, Vinicius; Souza, Caio; Treptow, Werner; Santos, Guilherme Martins

    2017-03-22

    Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to nucleosome. Our findings support that cholesterol assists 10nm and 30nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.

  13. Biliary cholesterol secretion: More than a simple ABC

    Institute of Scientific and Technical Information of China (English)

    Arne; Dikkers; Uwe; JF; Tietge

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophys...

  14. Biliary cholesterol secretion: More than a simple ABC

    OpenAIRE

    Dikkers, Arne; Tietge, Uwe JF

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the ...

  15. 总胆固醇水平对首发青年抑郁症患者认知功能的影响研究%Effects of total cholesterol level on the cognitive function in first-episode depression in young patients

    Institute of Scientific and Technical Information of China (English)

    周珊珊; 李宁; 刘维娟; 何津春; 张永霞

    2013-01-01

    Objective To study the effect of cholesterol levels within the normal range of serum cholesterol on cognitive function in patients with first-episode depression in youth.Methods 128 depression patients were divided into the study group and control group.The cognitive function were measured by WAIS-RC,Wechsler Memory Scale and Wisconsin Card Sorting Test (WCST).Resuits There were significant differences in some neuropsychological tests between experimental and control groups (P<0.05),such as digit span (9.74 ± 2.40,10.74 ± 2.91),pictures fill in the blank (5.54 ± 1.65,6.30 ± 1.91),visual recognition (8.07 ±2.35,8.98±2.76),and long term memory(35.28±6.87,51.32±13.41).For understanding(6.41±2.57,8.28±2.23)and persistent number of errors(69.02-11.42,54.11±12.92),there was significant difference between the two groups (P<0.01).Conclusion The cognitive level of the group of low serum total cholesterol is poor than that of the group of high serum total cholesterol.Low cholesterol level plays a certain role in depression suicide.Low level of cognition is important to assess depression suicide risk.%目的 探究正常血清总胆固醇(TC)范围内总胆固醇水平对首发青年抑郁症患者认知功能的影响.方法 将128例抑郁症患者分为研究组(3.1<TC<4.3 mmol/L)和对照组(4.3≤TC<5.5 mmol/L),然后对两组进行认知功能的对照性评估,用韦氏成人智能量表、韦氏记忆量表、威斯康星卡片分类测验评估其认知功能.结果 研究组的数字广度、图画填空、再认、长时记忆[分别为(9.74±2.40)分、(5.54±1.65)分、(8.07±2.35)分、(35.28±6.87)分]与对照组[分别为(10.74±2.91)分、(6.30±1.91)分、(8.98±2.76)分、(51.32±13.41)分],差异有统计学意义(P<0.05);研究组的理解和持续错误数[分别为(6.41±2.57)分,(69.02±11.42)分]与对照组[分别为(8.28±2.23)分、(54.11±12.92)分]差异有极显著性(P<0.01).结论 血清总胆固醇偏低组的认

  16. The 2013 cholesterol guideline controversy: Would better evidence prevent pharmaceuticalization?

    Science.gov (United States)

    Unruh, Lynn; Rice, Thomas; Rosenau, Pauline Vaillancourt; Barnes, Andrew J

    2016-07-01

    Cardiovascular disease (CVD) remains the leading cause of death globally. A class of medications, known as statins, lowers low-density lipoprotein cholesterol levels, which are associated with CVD. The newest 2013 U.S. cholesterol guideline contains an assessment of risk that greatly expands the number of individuals without CVD for whom statins are recommended. Other countries are also moving in this direction. This article examines the controversy surrounding these guidelines using the 2013 cholesterol guidelines as a case study of broader trends in clinical guidelines to use a narrow evidence base, expand the boundaries of disease and overemphasize pharmaceutical treatment. We find that the recommendation in the 2013 cholesterol guidelines to initiate statins in individuals with a lower risk of CVD is controversial and there is much disagreement on whether there is evidence for the guideline change. We note that, in general, clinical guidelines may use evidence that has a number of biases, are subject to conflicts of interest at multiple levels, and often do not include unpublished research. Further, guidelines may contribute to the "medicalization" or "pharmaceuticalization" of healthcare. Specific policy recommendations to improve clinical guidelines are indicated: these include improving the evidence base, establishing a public registry of all results, including unpublished ones, and freeing the research process from pharmaceutical sector control.

  17. Structure of Cholesterol in Lipid Rafts

    Science.gov (United States)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.

    2014-11-01

    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  18. Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

    Directory of Open Access Journals (Sweden)

    Xiaoyang Xu

    2015-08-01

    Full Text Available Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml 0 to 60. Methods: Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros

  19. Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase signaling in human eosinophils.

    Directory of Open Access Journals (Sweden)

    Mandy E Burnham

    Full Text Available Eosinophils function contributes to human allergic and autoimmune diseases, many of which currently lack curative treatment. Development of more effective treatments for eosinophil-related diseases requires expanded understanding of eosinophil signaling and biology. Cell signaling requires integration of extracellular signals with intracellular responses, and is organized in part by cholesterol rich membrane microdomains (CRMMs, commonly referred to as lipid rafts. Formation of these organizational membrane domains is in turn dependent upon the amount of available cholesterol, which can fluctuate widely with a variety of disease states. We tested the hypothesis that manipulating membrane cholesterol content in primary human peripheral blood eosinophils (PBEos would selectively alter signaling pathways that depend upon membrane-anchored signaling proteins localized within CRMMs (e.g., mitogen activated protein kinase [MAPK] pathway, while not affecting pathways that signal through soluble proteins, like the Janus Kinase/Signal Transducer and Activator of Transcription [JAK/STAT] pathway. Cholesterol levels were increased or decreased utilizing cholesterol-chelating methyl-β-cyclodextrin (MβCD, which can either extract membrane cholesterol or add exogenous membrane cholesterol depending on whether MβCD is preloaded with cholesterol. Human PBEos were pretreated with MβCD (cholesterol removal or MβCD+Cholesterol (MβCD+Chol; cholesterol delivery; subsequent IL-5-stimulated signaling and physiological endpoints were assessed. MβCD reduced membrane cholesterol in PBEos, and attenuated an IL-5-stimulated p38 and extracellular-regulated kinase 1/2 phosphorylation (p-p38, p-ERK1/2, and an IL-5-dependent increase in interleukin-1β (IL-1β mRNA levels. In contrast, MβCD+Chol treatment elevated PBEos membrane cholesterol levels and basal p-p38, but did not alter IL-5-stimulated phosphorylation of ERK1/2, STAT5, or STAT3. Furthermore, M

  20. Potential of BODIPY-cholesterol for analysis of cholesterol transport and diffusion in living cells

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Lund, Frederik Wendelboe; Röhrl, Clemens

    2016-01-01

    Cholesterol is an abundant and important lipid component of cellular membranes. Analysis of cholesterol transport and diffusion in living cells is hampered by the technical challenge of designing suitable cholesterol probes which can be detected for example by optical microscopy. One strategy...... is to use intrinsically fluorescent sterols, as dehydroergosterol (DHE), having minimal chemical alteration compared to cholesterol but giving low fluorescence signals in the UV region of the spectrum. Alternatively, one can use dye-tagged cholesterol analogs and in particular BODIPY-cholesterol (BChol......), whose synthesis and initial characterization was pioneered by Robert Bittman. Here, we give a general overview of the properties and applications but also limitations of BODIPY-tagged cholesterol probes for analyzing intracellular cholesterol trafficking. We describe our own experiences...

  1. Acrosome membrane integrity and cryocapacitation are related to cholesterol content of bull spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Srivastava N; Srivastava SK; Ghosh SK; Amit Kumar; Perumal P; Jerome A

    2013-01-01

    Objective: To evaluate the cryoinjury prediction of spermatozoa in relation to its cholesterol content at fresh and frozen-thaw stages. Methods: Ejaculates (n=12) were processed for cryopreservation, acrosome integrity (fluorescent and giemsa stains), cryoinjury (distribution of non capacitated, capacitated and acrosome reacted, pattern F, B and AR, respectively of Chlortetracycline, CTC assay), in vitro fertiltiy (IVF) and cholesterol content of spermatozoa at fresh, pre-freeze and frozen-thaw stages were evaluated. Values were fitted in prediction equation to predict acrosome integrity (AI) and cryoinjury. Results: Study indicated that cholesterol content of fresh spermatozoa can be used to predict cholesterol content of spermatozoa at pre-freeze and frozen-thaw stages of cryopreservation protocol with medium to high level of accuracy (P<0.05 and P<0.01, respectively). Cholesterol content of fresh spermatozoa can be used to predict AI, pattern B and AR and Penetration Index (PI) of IVF with medium level of accuracy (P<0.05) at frozen-thaw but not at pre-freeze stage. Similarly cholesterol content of frozen-thaw spermatozoa can be used to predict AI and pattern AR of frozen-thaw spermatozoa with medium level of accuracy (P<0.05). Conclusion: This study revealed strong evidence that cholesterol content of fresh as well as frozen-thaw bull spermatozoa can be a good predictor of level of cryoinjury following preservation at ultra low temperature.

  2. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Freiberg, Jacob J

    2011-01-01

    Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non......-fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

  3. Cholesterol changes in coronary patients after a short behavior modification program.

    Science.gov (United States)

    Sebregts, Ellen H; Falger, Paul R; Bär, Frits W; Kester, Arnold D; Appels, Ad

    2003-01-01

    Serum cholesterol changes after an 8-week behavior modification program for patients with coronary artery disease (CAD) were studied in a randomized controlled clinical trial. Acute myocardial infarction (AMI) or coronary artery bypass grafting (CABG) patients were randomly assigned to the intervention (N = 94) or to usual care (N = 90). After 9 months' follow-up the intervention was effective in reducing total cholesterol and LDL cholesterol levels, particularly in patients with high baseline lipid levels. After correcting for changes in dose of statins during follow-up, effects were weakened, but for patients with high baseline cholesterol levels favorable effects remained. In these patients, the intervention group showed a decline of total cholesterol and LDL cholesterol levels of 20% and 29%, respectively, compared to a 12% and 19% reduction in the control group (p <.01). These effects could not be explained by changes in dietary fat consumption. An unexpected finding was a lower increase in HDL cholesterol in the intervention group than in the control group.

  4. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Freiberg, Jacob J

    2011-01-01

    -fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

  5. Molecular mechanisms underlying the cholesterol-lowering effect of Ginkgo biloba extract in hepatocytes: a comparative study with Iovastatin

    Institute of Scientific and Technical Information of China (English)

    Zuo-quan XIE; Gai LIANG; Lu ZHANG; Qi WANG; Yi QU; Yang GAO; Li-bo LIN; Sai YE; Ji ZHANG; Hui WANG; Guo-ping ZHAO; Qing-hua ZHANG

    2009-01-01

    Aim: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE). Methods: Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or Iovastatin. Results: GBE decreased the total cholesterol content in cultured hepatocytes and inhibited the activity of HMG-CoA reductase, as determined by an in vitro enzyme activity assay. In addition, GBE decreased cholesterol influx, whereas Iovastatin increased choles-terol influx. GBE treatment induced significant increases in the expression of cholesterogenic genes and genes involved in cholesterol metabolism, such as SREBF2, as determined by cDNA microarray and real-time RT-PCR. Furthermore, INSIG2, LDLR, LRP1, and LRP10 were differentially regulated by GBE and Iovastatin. The data imply that the two compounds modulate cholesterol metabolism through distinct mechanisms. Conclusion: By using a gene expression profiling approach, we were able to broaden the understanding of the molecular mechanisms by which GBE lowers cellular cholesterol levels. Specifically, we demonstrated that GBE exhibited dual effects on the cellular choles-terol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx.

  6. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice.

    Science.gov (United States)

    Thacker, Seth G; Rousset, Xavier; Esmail, Safiya; Zarzour, Abdalrahman; Jin, Xueting; Collins, Heidi L; Sampson, Maureen; Stonik, John; Demosky, Stephen; Malide, Daniela A; Freeman, Lita; Vaisman, Boris L; Kruth, Howard S; Adelman, Steven J; Remaley, Alan T

    2015-07-01

    LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification. Scarab(-/-)×LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(-/-)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(-/-)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(-/-)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(-/-) mice (P esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles.

  7. Efectos de una intervención educativa sobre los niveles plasmáticos de LDL-colesterol en diabéticos tipo 2 Effects of an educational intervention on plasma levels of LDL cholesterol in type-2 diabetics

    Directory of Open Access Journals (Sweden)

    Carlos Enrique Cabrera-Pivaral

    2001-12-01

    Full Text Available Objetivo. Demostrar las ventajas de una intervención educativa en el control del colesterol de baja densidad (LDL colesterol en el paciente diabético tipo 2. Material y métodos. Se realizó un estudio cuasi experimental con asignación aleatoria de dos grupos de pacientes diabéticos: un grupo de experimento y un grupo control. El grupo de experimento se integró con 25 diabéticos tipo 2 y el control con 24. La intervención educativa-participativa se organizó mediante el proceso de reflexión-acción. Se efectuaron mediciones de los niveles séricos del LDL colesterol basales y mensuales durante los nueve meses de la intervención educativa. Los grupos fueron controlados tomando en cuenta edad y sexo. El análisis estadístico se efectuó con el estadígrafo de Wilcoxon para variables ordinales y grupos relacionados. Resultados. El grupo que recibe la intervención educativa participativa logra un valor promedio de 148.4+/-21.3, en comparación con el grupo control (185+/-24.1 en la medición posterior del colesterol LDL (p£0.05. Conclusiones. La intervención educativa participativa, mediante la promoción de un nuevo estilo de vida en el paciente diabético del tipo 2, contribuye a mejorar el nivel de control metabólico del LDL colesterol. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjective. To prove the benefit of an educational intervention for controlling LDL cholesterol levels in LDL cholesterol. Material and Methods. A quasi-experimental study was conducted; diabetic patients were randomly allocated to an experimental and a control group. The experimental group consisted of 25 patients and the control group of 24 patients. The educational intervention was organized through a reflection-action process. LDL cholesterol levels were measured at baseline and monthly during the nine months of the study. The groups were controlled for age and sex. Statistical analysis included

  8. Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Liscum, L.; Ruggiero, R.M.; Faust, J.R.

    1989-05-01

    Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived (3H)cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of (3H)acetate-derived, endogenously synthesized (3H)cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived (3H)cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol.

  9. Comparative effects of hawthorn (Crataegus pinnatifida Bunge) pectin and pectin hydrolyzates on the cholesterol homeostasis of hamsters fed high-cholesterol diets.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Li, Tuo-Ping; Chen, Gang; Peng, Xue; Duan, Wen-Bin; Zheng, Zheng-Zheng; Shi, Shu-Lei; Xu, Jing-Guo; Liu, Yan-Hua; Jin, Xiao-Yi

    2015-08-05

    This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism.

  10. From blood to gut : Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  11. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A M; Vonk, R J; Niezen-Koning, K; Berger, R.; Fernandes, J

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  12. Molecular dynamics simulations on the interaction of the transmembrane NavAb channel with cholesterol and lipids in the membrane.

    Science.gov (United States)

    Suwattanasophon, Chonticha; Wolschann, Peter; Faller, Roland

    2016-01-01

    Increased cholesterol levels are associated with multiple pathological conditions. In this work, molecular dynamics simulations were applied to observe the influence of membrane cholesterol levels on a voltage-gated sodium channel. Different lipid compositions are modeled around the channel to obtain information about the possible effects by which cholesterol influences NavAb channels. Cholesterol was normally not directly interacting with either the closed or inactivated conformation. Cholesterol increased lipid packing implying that it plays a crucial role in restricting lipid movement in the region around 1 nm of the channel in a 1-palmitoyl-2-oeleoyl phosphatidylcholine matrix. Our results provide the first computational indication of an indirect modulation of NavAb channels by membrane cholesterol.

  13. Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

    Science.gov (United States)

    Zhong, Chun-Yan; Sun, Wei-Wei; Ma, Yinyan; Zhu, Hongling; Yang, Pan; Wei, Hong; Zeng, Ben-Hua; Zhang, Qian; Liu, Yu; Li, Wen-Xia; Chen, Yixin; Yu, Liqing; Song, Zhi-Yuan

    2015-05-27

    We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.

  14. Rice Protein Extracted by Different Methods Affects Cholesterol Metabolism in Rats Due to Its Lower Digestibility

    Directory of Open Access Journals (Sweden)

    Hongbo Liu

    2011-11-01

    Full Text Available To elucidate whether the digestibility is responsible for the hypocholesterolemic action of rice protein, the effects of rice proteins extracted by alkali (RP-A and α-amylase (RP-E on cholesterol metabolism were investigated in 7-week-old male Wistar rats fed cholesterol-free diets for 3 weeks. The in vitro and in vivo digestibility was significantly reduced by RP-A and RP-E as compared to casein (CAS. The digestibility was lower in RP-E than that of RP-A. Compared with CAS, the significant cholesterol-lowering effects were observed in rats fed by RP-A and RP-E. Fecal excretion of bile acids was significantly stimulated by RP-E, but not by RP-A. The apparent cholesterol absorption was more effectively inhibited by RP-E than RP-A because more fecal neutral sterols were excreted in rats fed RP-E. There was a significant correlation between protein digestibility and cholesterol absorption (r = 0.8662, P < 0.01, resulting in a significant correlation between protein digestibility and plasma cholesterol level (r = 0.7357, P < 0.01 in this study. The present study demonstrates that the digestibility of rice protein affected by extraction method plays a major role in the modulation of cholesterol metabolism. Results suggest that the hypocholesterolemic action induced by rice protein with lower digestibility primarily contribute to the inhibition of cholesterol absorption.

  15. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

    Science.gov (United States)

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-06-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

  16. Relationship between changes in mRNAs of the genes encoding steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage in head kidney and plasma levels of cortisol in response to different kinds of acute stress in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Geslin, Malika; Auperin, Benoit

    2004-01-01

    In this study, the expression of several genes involved in cortisol synthesis in head kidneys, the site of cortisol production, and in the rainbow trout (Oncorhynchus mykiss) was examined in response to two different acute stressors and an acute ACTH treatment. mRNAs levels of the "steroidogenic acute regulatory" (StAR) sterol transport protein, which transports cholesterol to the inner mitochondrial membrane as well as cytochrome P450 cholesterol side chain cleavage (P450(SCC)) were determined in head kidney (containing the interrenal tissue). In one experiment, we also quantified 3-beta-hydroxysteroid dehydrogenase (3B-HSD) and cytochrome P450(11beta) (11B-H) mRNAs. The presence of these four transcripts in the head kidney was confirmed by Northern blot analysis. For each stress condition, mRNA levels were quantified by quantitative or real-time RT-PCR. The results of these two methods were highly correlated. An acute stress induced by capture, short confinement (2min), and anesthesia (3min) resulted in significant elevation of plasma cortisol (30-fold higher than controls) and an increase in levels of StAR and P450(SCC) mRNAs 3h post-stress. When fish were submitted to an acute stress caused by 5min of chase with a net in a tank, plasma cortisol reached a peak within 1h, but after 3h, levels were only 5-fold higher in stressed trout than in controls and no variations in the expression of StAR, P450(SCC), 3B-HSD, and 11B-H were observed whatever the time post-stress. One hour after acute ACTH stimulation (5IU/kg), plasma cortisol level was 4-fold higher than in control trout and no changes in StAR and P450(SCC) mRNAs levels were detected. The data suggest that the high levels of cortisol after stress need an activation of genes involved in cortisol synthesis, but lower levels do not. Futhermore, under these three test conditions, we always found a strong positive correlation between mRNA levels of StAR and P450(SCC), in contrast to what has been described in

  17. Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis.

    Science.gov (United States)

    Papadopoulos, Vassilios; Aghazadeh, Yasaman; Fan, Jinjiang; Campioli, Enrico; Zirkin, Barry; Midzak, Andrew

    2015-06-15

    Steroidogenesis begins with cholesterol transfer into mitochondria through the transduceosome, a complex composed of cytosolic proteins that include steroidogenesis acute regulatory protein (STAR), 14-3-3 adaptor proteins, and the outer mitochondrial membrane proteins Translocator Protein (TSPO) and Voltage-Dependent Anion Channel (VDAC). TSPO is a drug- and cholesterol-binding protein found at particularly high levels in steroid synthesizing cells. Its aberrant expression has been linked to cancer, neurodegeneration, neuropsychiatric disorders and primary hypogonadism. Brain steroids serve as local regulators of neural development and excitability. Reduced levels of these steroids have been linked to depression, anxiety and neurodegeneration. Reduced serum testosterone is common among subfertile young men and aging men, and is associated with depression, metabolic syndrome and reduced sexual function. Although testosterone-replacement therapy is available, there are undesired side-effects. TSPO drug ligands have been proposed as therapeutic agents to regulate steroid levels in the brain and testis.

  18. Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats.

    Science.gov (United States)

    Zhang, X; Beynen, A C

    1993-05-01

    The effects of amount and type of dietary fish proteins on plasma and liver cholesterol concentrations were evaluated in female rats. The isonitrogenous diets used contained 10 g cholesterol/kg and were carefully balanced for residual fat, cholesterol, Ca, Mg and P in the protein preparations. Cod meal, soya-bean protein or casein was incorporated into the diets as the only source of dietary protein at three levels: either 24, 48 or 72 g N/kg diet. Extra protein was added to the diet at the expense of the glucose component. In a second experiment soya-bean protein, casein, cod meal, whiting meal or plaice meal was added to the diet at a level of 24 g N/kg. When compared with casein, cod meal and soya-bean protein decreased plasma and liver cholesterol concentrations. A further cholesterol-lowering effect was achieved by increasing the proportion of either soya-bean protein or cod meal in the diet. Substitution of casein for glucose did not influence plasma and liver cholesterol concentrations. Plaice meal in the diet produced lower group mean plasma cholesterol concentrations than did whiting meal. In rats fed on the diet containing plaice meal, liver cholesterol concentrations were significantly lower than those in their counterparts fed on either cod meal or whiting meal. The present study demonstrates that different fish proteins in the diet have different effects on cholesterol metabolism and that the cholesterol-influencing properties of cod meal can be enhanced by the incorporation of higher proportions of this protein in the diet.

  19. Tumor-Suppressor Function of SPARC-Like Protein 1/Hevin in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Irene Esposito

    2007-01-01

    Full Text Available SPARC-like protein 1 (SPARCL1, a member of the SPARC family, is downregulated in various tumors. In the present study, the expression and localization of SPARCL1 were analyzed in a wide range of nontumorous and neoplastic pancreatic tissues by quantitative reverse transcription-polymerase chain reaction, laser capture microdissection, microarray analysis, and immunohistochemistry. For functional analysis, proliferation and invasion assays were used in cultured pancreatic cancer cells. Pancreatic ductal adenocarcinoma (PDAC and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its antiinvasive effects and reduced expression in metastasis indicate tumor-suppressor function.

  20. Cholesterol orientation and tilt modulus in DMPC bilayers

    OpenAIRE

    Khelashvili, George; Pabst, Georg; Harries, Daniel

    2010-01-01

    We performed molecular dynamics (MD) simulations of hydrated bilayers containing mixtures of dimyristoylphosphatidylcholine (DMPC) and Cholesterol at various ratios, to study the effect of cholesterol concentration on its orientation, and to characterize the link between cholesterol tilt and overall phospholipid membrane organization. The simulations show a substantial probability for cholesterol molecules to transiently orient perpendicular to the bilayer normal, and suggest that cholesterol...

  1. Cholesterol remnants and triglycerides are associated with decreased myocardial function in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Jørgensen, Peter Godsk; Jensen, Magnus Thorsten; Biering-Sørensen, Tor;

    2016-01-01

    BACKGROUND: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive echocardiogra......BACKGROUND: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive...... secondary care centers. RESULTS: In multivariable analyses, triglycerides and cholesterol remnants were not associated with left ventricular ejection fraction, but with subtle measures of systolic function, including global longitudinal strain by speckle tracking and longitudinal displacement by tissue...... Doppler echocardiography: global longitudinal strain [0.33 % (0.14), p = 0.02 per doubling in cholesterol remnants and 0.28 % (0.13), p = 0.03 per doubling in triglyceride levels] and with longitudinal displacement [-0.25 mm (0.10), p = 0.01 per doubling in cholesterol remnants and -0.25 mm (0.09), p = 0...

  2. Protonated nanostructured aluminosilicate (NSAS reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

    Directory of Open Access Journals (Sweden)

    Constantinides Panayiotis P

    2009-07-01

    Full Text Available Abstract The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w, untreated control and 2% (w/w stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w and stigmastanol at 2% (w/w treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w NSAS and 2% (w/w stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

  3. Community-wide survey of physicians' knowledge of cholesterol management

    Institute of Scientific and Technical Information of China (English)

    GUAN Fei; XIE Jiang; WANG Gui-lian; WANG Jia-hong; WANG Jin-song; YU Jin-ming; HU Da-yi

    2010-01-01

    Background An elevated serum lipid is one of the major risk factors for coronary heart disease (CHD). Physicians' awareness contributes to successful adoption of practice guidelines. Community medical centers are the primary defense against chronic disease. This study aimed to investigate community physicians' awareness of cholesterol guidelines and their utilization.Methods Six hundred and one community physicians were randomly selected from four different regions, and completed a confidential and semi-structured questionnaire. Four hundred and ninety-one completed the questionnaire, and 486 valid questionnaires were available.Results The physicians' fundamental knowledge of lipids was astonishingly poor, while the awareness of cholesterol guidelines was low. Only 24% and 14% of the physicians reported the right optimal low-density lipoprotein cholesterol (LDL-C) level for CHD and diabetes patients respectively. More than half of the physicians (55.8%) mistakenly considered elevated transaminases to be the lethal side effect of statins. More than half of the physicians (51.9%) would give up statin treatment in the case of transaminase elevation.Conclusion Educational interventions to improve cholesterol knowledge and to publicize standard treatment are needed among Chinese community physicians.

  4. Effect of phosphatidylcholine-cholesterol liposomes on Entamoeba histolytica virulence.

    Science.gov (United States)

    Serrano-Luna, Jesús; Gutiérrez-Meza, Manuel; Mejía-Zepeda, Ricardo; Galindo-Gómez, Silvia; Tsutsumi, Víctor; Shibayama, Mineko

    2010-12-01

    Trophozoites of Entamoeba histolytica HM-1:IMSS become less virulent after long-term maintenance in axenic cultures. The factors responsible for the loss of virulence during in vitro cultivation remain unclear. However, it is known that in vitro cultivation of amoeba in culture medium supplemented with cholesterol restores their virulence. In this study, we analyzed the effect of adding phosphatidylcholine-cholesterol (PC-Chol) liposomes to the culture medium and evaluated the effect of this lipid on various biochemical and biological functions of E. histolytica HM-1:IMSS in terms of its virulence. The addition of PC-Chol liposomes to the culture medium maintained the virulence of these parasites against hamster liver at the same level as the original virulent E. histolytica strain, even though these amoebae were maintained without passage through hamster liver for 18 months. The trophozoites also showed increased endocytosis, erythrophagocytosis, and carbohydrate residue expression on the amoebic surface. Protease activities were also modified by the presence of cholesterol in the culture medium. These findings indicate the capacity of cholesterol to preserve amoeba virulence and provide an alternative method for the maintenance of virulent E. histolytica trophozoites without the need for in vivo procedures.

  5. The effect of cellular cholesterol on membrane-cytoskeleton adhesion.

    Science.gov (United States)

    Sun, Mingzhai; Northup, Nathan; Marga, Francoise; Huber, Tamas; Byfield, Fitzroy J; Levitan, Irena; Forgacs, Gabor

    2007-07-01

    Whereas recent studies suggest that cholesterol plays important role in the regulation of membrane proteins, its effect on the interaction of the cell membrane with the underlying cytoskeleton is not well understood. Here, we investigated this by measuring the forces needed to extract nanotubes (tethers) from the plasma membrane, using atomic force microscopy. The magnitude of these forces provided a direct measure of cell stiffness, cell membrane effective surface viscosity and association with the underlying cytoskeleton. Furthermore, we measured the lateral diffusion constant of a lipid analog DiIC12, using fluorescence recovery after photobleaching, which offers additional information on the organization of the membrane. We found that cholesterol depletion significantly increased the adhesion energy between the membrane and the cytoskeleton and decreased the membrane diffusion constant. An increase in cellular cholesterol to a level higher than that in control cells led to a decrease in the adhesion energy and the membrane surface viscosity. Disassembly of the actin network abrogated all the observed effects, suggesting that cholesterol affects the mechanical properties of a cell through the underlying cytoskeleton. The results of these quantitative studies may help to better understand the biomechanical processes accompanying the development of atherosclerosis.

  6. Genetic variation in the ABCA1 gene, HDL cholesterol, and risk of ischemic heart disease in the general population

    DEFF Research Database (Denmark)

    Frikke-Schmidt, Ruth

    2010-01-01

    Epidemiological studies consistently demonstrate a strong inverse association between low levels of high-density lipoprotein (HDL) cholesterol and increased risk of ischemic heart disease (IHD). This review focuses on whether both rare and common genetic variation in ABCA1 contributes to plasma...... levels of HDL cholesterol and to risk of IHD in the general population, and further seeks to understand whether low levels of HDL cholesterol per se are causally related to IHD. Studies of the ABCA1 gene demonstrate a general strategy for detecting functional genetic variants, and show that both common...... and rare ABCA1 variants contribute to levels of HDL cholesterol and risk of IHD in the general population. The association between ABCA1 variants and risk of IHD appears, however, to be independent of plasma levels of HDL cholesterol. With the recent identification of the largest number of individuals...

  7. Cholesterol, the central lipid of mammalian cells

    NARCIS (Netherlands)

    Maxfield, F. R.; van Meer, G.

    2010-01-01

    Despite its importance for mammalian cell biology and human health, there are many basic aspects of cholesterol homeostasis that are not well understood. Even for the well-characterized delivery of cholesterol to cells via lipoproteins, a novel regulatory mechanism has been discovered recently, invo

  8. Evaluating computational models of cholesterol metabolism

    NARCIS (Netherlands)

    Paalvast, Yared; Kuivenhoven, Jan Albert; Groen, Albert K.

    2015-01-01

    Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of chol

  9. 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages

    Directory of Open Access Journals (Sweden)

    Sapir Bechor

    2016-07-01

    Full Text Available Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc is a precursor for 9-cis-retinoic-acid (9-cis-RA, which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-βc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with βc from the alga Dunaliella led to βc accumulation in peritoneal macrophages. 9-cis-βc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from βc in RAW264.7 macrophages. Furthermore, 9-cis-βc, as well as all-trans-βc, significantly increased cholesterol efflux to high-density lipoprotein (HDL by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-βc augmented cholesterol efflux from macrophages ex vivo. 9-cis-βc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-βc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of βc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages.

  10. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers...... in a monoclinic cholesterol . H2O phase, has been monitored and their structures characterized to near atomic resolution. Crystallographic evidence is presented that this multilayer phase is similar to that of a reported metastable cholesterol phase of undetermined structure obtained from bile before...... transformation to the triclinic phase of cholesterol . H2O, the thermodynamically stable macroscopic form. According to grazing incidence x-ray diffraction measurements and crystallographic data, a transformation from the monoclinic film structure to a multilayer of the stable monohydrate phase involves...

  11. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C

    2014-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  12. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    Science.gov (United States)

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids.

  13. Anti-cholesterol activity test of tanjung (Mimusops elengi L.) leaf extract in the water using in vivo method in mice (Mus musculus L.) DDY-strain

    Science.gov (United States)

    Tristantini, Dewi; Pradana, Bhayangkara Tegar

    2017-02-01

    High cholesterol level in blood is one of deadly cardiovascular disease's causes which is triggered by accumulation of cholesterol patching in blood vessels through heart and using synthetic medicine has several side effect. However, tanjung (M. elengi) which abundant in Indonesia is believed that it can strengthen and clean plaque in blood vessels wall. In this study, anti-cholesterol activity of tanjung (M. elengi) leaf extract in the water will be tested by in vivo method to 6 group of mice (Mus musculus) DDY-strain. The result showed that tanjung (M. elengi) leaf extract has significant effect to decrease total cholesterol level of mice, more extract given to mice, it will give higher cholesterol decreasing. TE 3 can decrease cholesterol level as much as 36%. In this study, it can be concluded that tanjung (M. elengi) leaf extract can be used as cholesterol decreasing medicine.

  14. Variation of the cholesterol content in breast milk during 10 days collection at early stages of lactation.

    Science.gov (United States)

    Kamelska, Anna M; Pietrzak-Fiećko, Renata; Bryl, Krzysztof

    2012-01-01

    More and more research is done concerning nutritional programming. Human milk nutrients which are consumed by infants can influence their health in later life. High level of cholesterol in human milk paradoxically lowers the cholesterol concentration in blood in adults. During the course of human lactation the cholesterol concentration decreases from 31 mg/100cm(3) (colostrum) to 16 mg/100 cm(3) (mature milk). According to Scopesi et al., 2002, Clin Nutr 21: 379-384, cholesterol concentration in mature milk ranged from 6.5 to 18.4 mg/100 cm(3). The aim of the study was to assess the variations in breast milk cholesterol content during 10 day collection at early lactation. 48 samples of human milk were analyzed. Mean age of women was 31 years. Women were collecting samples during 10 days of an early lactation stage (1-3 months after delivery). An Attenuated Total Reflectance Fourier Transformed Infrared (FTIR-ATR) method for easy and rapid determination of cholesterol in human milk was elaborated. Cholesterol content assessed by the FTIR method ranged from 3.36 to 12.98 mg/100 cm(3). Results indicate that milk cholesterol concentration during 10 consecutive days of early lactation is highly variable. Cholesterol content depends on an individual. Therefore it is suggested that not only the period of lactation but also mother's diet, age, season and place of residence are important factors determining cholesterol content.

  15. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, Rebecca; Zeino, Maen [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Frewert, Simon [Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, Saarbrücken (Germany); Efferth, Thomas, E-mail: efferth@uni-mainz.de [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany)

    2014-11-15

    Treatment of glioblastoma multiforme (GBM), the most common and aggressive lethal brain tumor, represents a great challenge. Despite decades of research, the survival prognosis of GBM patients is unfavorable and more effective therapeutics are sorely required. Archazolid B, a potent vacuolar H{sup +}-ATPase inhibitor influencing cellular pH values, is a promising new compound exerting cytotoxicity in the nanomolar range on wild-type U87MG glioblastoma cells and U87MG.∆EGFR cells transfected with a mutant epidermal growth factor receptor (EGFR) gene. Gene expression profiling using microarray technology showed that archazolid B caused drastic disturbances in cholesterol homeostasis. Cholesterol, a main component of cellular membranes, is known to be essential for GBM growth and cells bearing EGFRvIII mutation are highly dependent on exogenous cholesterol. Archazolid B caused excessive accumulation of free cholesterol within intracellular compartments thus depleting cellular cholesterol and leading to up-regulation of SREBP targeted genes, including LDLR and HMGCR, the key enzyme of cholesterol biosynthesis. This cholesterol response is considered to be a novel resistance mechanism induced by archazolid B. We surmise that re-elevation of cholesterol levels in archazolid B treated cells may be mediated by newly synthesized cholesterol, since the drug leads to endosomal/lysosomal malfunction and cholesterol accumulation.

  16. Cholesterol: Top Five Foods to Lower Your Numbers

    Science.gov (United States)

    Cholesterol: Top foods to improve your numbers Diet can play an important role in lowering your cholesterol. Here are the top foods to lower your cholesterol and protect your heart. By Mayo Clinic Staff ...

  17. Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro.

    Science.gov (United States)

    Lammel Lindemann, Jan A; Angajala, Anusha; Engler, David A; Webb, Paul; Ayers, Stephen D

    2014-05-05

    Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor β1 (TRβ1) in liver to regulate metabolic gene sets. In rodents, one important TH regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450 family, which enhances cholesterol to bile acid conversion and plays a crucial role in regulation of serum cholesterol levels. Current models suggest, however, that Cyp7a1 has lost the capacity to respond to THs in humans. We were prompted to re-examine TH effects on cholesterol metabolic genes in human liver cells by a recent study of a synthetic TH mimetic which showed that serum cholesterol reductions were accompanied by increases in a marker for bile acid synthesis in humans. Here, we show that TH effects upon cholesterol metabolic genes are almost identical in mouse liver, mouse and human liver primary cells and human hepatocyte cell lines. Moreover, Cyp7a1 is a direct TR target gene that responds to physiologic TR levels through a set of distinct response elements in its promoter. These findings suggest that THs regulate cholesterol to bile acid conversion in similar ways in humans and rodent experimental models and that manipulation of hormone signaling pathways could provide a strategy to enhance Cyp7a1 activity in human patients.

  18. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and b

  19. Impact of the loss of caveolin-1 on lung mass and cholesterol metabolism in mice with and without the lysosomal cholesterol transporter, Niemann-Pick type C1.

    Science.gov (United States)

    Mundy, Dorothy I; Lopez, Adam M; Posey, Kenneth S; Chuang, Jen-Chieh; Ramirez, Charina M; Scherer, Philipp E; Turley, Stephen D

    2014-07-01

    Caveolin-1 (Cav-1) is a major structural protein in caveolae in the plasma membranes of many cell types, particularly endothelial cells and adipocytes. Loss of Cav-1 function has been implicated in multiple diseases affecting the cardiopulmonary and central nervous systems, as well as in specific aspects of sterol and lipid metabolism in the liver and intestine. Lungs contain an exceptionally high level of Cav-1. Parameters of cholesterol metabolism in the lung were measured, initially in Cav-1-deficient mice (Cav-1(-/-)), and subsequently in Cav-1(-/-) mice that also lacked the lysosomal cholesterol transporter Niemann-Pick C1 (Npc1) (Cav-1(-/-):Npc1(-/-)). In 50-day-old Cav-1(-/-) mice fed a low- or high-cholesterol chow diet, the total cholesterol concentration (mg/g) in the lungs was marginally lower than in the Cav-1(+/+) controls, but due to an expansion in their lung mass exceeding 30%, whole-lung cholesterol content (mg/organ) was moderately elevated. Lung mass (g) in the Cav-1(-/-):Npc1(-/-) mice (0.356±0.022) markedly exceeded that in their Cav-1(+/+):Npc1(+/+) controls (0.137±0.009), as well as in their Cav-1(-/-):Npc1(+/+) (0.191±0.013) and Cav-1(+/+):Npc1(-/-) (0.213±0.022) littermates. The corresponding lung total cholesterol contents (mg/organ) in mice of these genotypes were 6.74±0.17, 0.71±0.05, 0.96±0.05 and 3.12±0.43, respectively, with the extra cholesterol in the Cav-1(-/-):Npc1(-/-) and Cav-1(+/+):Npc1(-/-) mice being nearly all unesterified (UC). The exacerbation of the Npc1 lung phenotype and increase in the UC level in the Cav-1(-/-):Npc1(-/-) mice imply a regulatory role of Cav-1 in pulmonary cholesterol metabolism when lysosomal sterol transport is disrupted.

  20. Cholesterol-Loaded Cyclodextrin Increases the Cholesterol Content of Goat Sperm to Improve Cold and Osmotic Resistance and Maintain Sperm Function after Cryopreservation.

    Science.gov (United States)

    Salmon, Vianney M; Leclerc, Pierre; Bailey, Janice L

    2016-04-01

    The success of semen cryopreservation depends on sperm membrane integrity and function after thawing. Cholesterol-loaded cyclodextrin (CLC) is used for in vitro incorporation of cholesterol to protect cells against cold temperatures. We hypothesized that CLC treatment also enhances sperm cholesterol content to increase tolerance to osmotic shock and cryoresistance, thereby improving fertility. We confirmed the fact that treatment of goat semen with 3 mg/ml CLC increases sperm cholesterol content using both the Liebermann-Burchard approach and filipin III labeling of membrane cholesterol. Sperm were then treated with or without CLC and cryopreserved. After thawing, sperm cholesterol dramatically fell, even in the presence of CLC, which explains the mechanism of cryocapacitation. CLC treatment, however, maintained a normal prefreeze cholesterol level in sperm after cryopreservation. Furthermore, fresh sperm treated with CLC and subjected to either cold shock or incubated in hypo-, iso-, and hyperosmotic media, designed to mimic stresses associated with freezing/thawing, displayed increased temperature and osmoti