WorldWideScience

Sample records for phytostanols decrease cholesterol

  1. The Food Matrix and Sterol Characteristics Affect the Plasma Cholesterol Lowering of Phytosterol/Phytostanol1

    Science.gov (United States)

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S.

    2013-01-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c. PMID:24228192

  2. The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

    Science.gov (United States)

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

    2013-11-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

  3. Can cholesterol absorption be reduced by phytosterols and phytostanols via a cocrystallization mechanism?

    Science.gov (United States)

    Mel'nikov, Sergey M; Seijen ten Hoorn, Jack W M; Bertrand, Benoit

    2004-01-01

    The formation of mixed water-insoluble poorly absorbable crystals between cholesterol (CH) and phytosterols (PS) or phytostanols (PSS) in the intestinal lumen has been considered for a long time as a plausible mechanism of the PS/PSS-induced reduction of serum CH concentration. In this report, we demonstrated with the use of the powder X-ray diffraction (XRD) and the differential scanning calorimetry (DSC) techniques that mixed CH:beta-sitosterol (SI) crystals can be formed by recrystallization of corresponding mixtures from melts and also from mixed CH:SI solutions in triglyceride oil. Formation of mixed CH:SI crystals takes place in a wide interval of CH:SI ratios, from approximately 10 up to approximately 75 wt.% of SI in the mixture. Formation of mixed CH:sitostanol (SS) crystals from melts and solutions in triglyceride oil was also detected, but in a more narrow interval of CH:SS ratios. However, during the lipolysis of model dietary emulsions under in vitro conditions, the formation of crystalline material was not detected due to the relatively high solubility of free sterols/stanols in products of fat hydrolysis. We found that the solubility of free CH, SI, and SS raises upon the increase in the solvent polarity, i.e. free fatty acid > diglycerideoil > triglyceride oil. Therefore, we believe that the cocrystallization mechanism of phytosterol-induced serum CH lowering has relatively low importance, unless the diet is specially designed to include relatively little amounts of dietary fats. The presented experimental evidence demonstrates that it is unlikely that the formation of poorly absorbable mixed crystals largely affects the intestinal absorption of CH and, therefore, that this is a prime mechanism by which PS and PSS effect CH absorption.

  4. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

    Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

  5. Analysis of pecan nut (Carya illinoinensis) unsaponifiable fraction. Effect of ripening stage on phytosterols and phytostanols composition.

    Science.gov (United States)

    Bouali, Intidhar; Trabelsi, Hajer; Herchi, Wahid; Martine, Lucy; Albouchi, Ali; Bouzaien, Ghaith; Sifi, Samira; Boukhchina, Sadok; Berdeaux, Olivier

    2014-12-01

    Changes in 4-desmethylsterol, 4-monomethylsterol, 4,4-dimethylsterol and phytostanol composition were quantitatively and qualitatively investigated during the ripening of three varieties of Tunisian-grown pecan nuts (Mahan, Moore and Burkett). These components have many health benefits, especially in lowering LDL-cholesterol and preventing heart disease. The phytosterol composition of whole pecan kernel was quantified by Gas Chromatography-Flame Ionisation Detection (GC-FID) and identified by Gas Chromatography-Mass Spectrometry (GC-MS). Fifteen phytosterols and one phytostanol were quantified. The greatest amount of phytosterols (2852.5mg/100g of oil) was detected in Mahan variety at 20 weeks after the flowering date (WAFD). Moore had the highest level of phytostanols (7.3mg/100g of oil) at 20 WAFD. Phytosterol and phytostanol contents showed a steep decrease during pecan nut development. Results from the quantitative characterisation of pecan nut oils revealed that β-sitosterol, Δ5-avenasterol, and campesterol were the most abundant phytosterol compounds at all ripening stages.

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. [Recomendations for clinical use of food enriched phytosterols/phytostanols handling hypercholesterolemia].

    Science.gov (United States)

    Merino, Jordi; Masana, Luis; Guijarro, Carlos; Ascaso, Juan; Lagares, Manuel; Civeira, Fernando

    2014-01-01

    Raised low-density lipoprotein cholesterol (LDLc) plasma concentration is a major risk factor for atherosclerotic cardiovascular disease. Despite international recommendations on hypercholesterolemia management the percentage of individuals with LDLc plasma concentration above goals according to their global cardiovascular risk remains high, and additional therapeutic strategies should be evaluated. Consumption of functional foods enriched with phytosterols (PSRs) and phytostanols (PSNs) reduces LDLc concentrations by 10% as average. Although recommended as part of any lipid-lowering diet in the first intervention step, PSRs/PSNs maintain their LDL reduction capacity when administered with lipid-lowering drugs; therefore, they can be also considered in some cases as an adjuvant to drug therapy. In this document we summarise the latest evidence regarding the LDL reducing effects of PSR/PSN supplementation, alone or as an add-on to hipolipemic drugs and the international recommendations of its clinical use. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  11. Decreased Retinol Binding Protein 4 Concentrations are Associated With Cholesterol Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Shen-Nien Wang

    2010-06-01

    Conclusion: Circulating RBP4 decreases in cholesterol gallstone disease independent of renal function. Further studies are needed to investigate the relationship between liver function and RBP4 levels in these patients.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. A reversal of decreasing trends in population cholesterol levels in Västerbotten County, Sweden

    Directory of Open Access Journals (Sweden)

    Margareta Norberg

    2012-03-01

    Full Text Available Background:High cholesterol is identified as a major risk factor for chronic non-communicable diseases, especially cardiovascular and cerebrovascular diseases. Monitoring trends of cholesterol levels and comparing trends across population groups are important to assess population distribution and risks related to cholesterol change over time. Cholesterol surveillance data are lacking, even in high-income countries.Objectives:To describe the trends in cholesterol and triglyceride levels in different population groups and to estimate the risk of developing hypercholesterolemia and hypertriglyceridemia in Västerbotten County, Sweden during 1990–2010.Designs and Methods:Since 1990, 133,082 individuals living in Västerbotten County, Northern Sweden, invited on their 30th, 40th, 50th and 60th birthdays, participated in the Västerbotten Intervention Program. Ten years after baseline data collection, 34,868 individuals were surveyed for a second time. In addition to a self-administered health questionnaire (that included information on socioeconomic status, demographics, self-reported health and lifestyle behaviours, blood cholesterol and triglyceride were examined.Results:The level and prevalence of hypercholesterolemia decreased significantly from 1990 to 2007, but the trends began to increase during 2008–2010 in men, women, and in all educational groups. Men had significantly higher serum triglyceride levels than women and their cholesterol levels were similar to those of the women. This study shows that those with basic education and who live in rural inlands had consistently higher triglyceride level than those who live in the city and have higher educational attainments. People with basic education are also at higher risk of developing hypercholesterolemia and hypertriglyceridemia at 10-year follow-up; the risk is much higher among the older cohorts, particularly women. During 1990–2010, the proportion of participants who reported

  15. A reversal of decreasing trends in population cholesterol levels in Västerbotten County, Sweden

    Science.gov (United States)

    Ng, Nawi; Johnson, Owe; Lindahl, Bernt; Norberg, Margareta

    2012-01-01

    Background High cholesterol is identified as a major risk factor for chronic non-communicable diseases, especially cardiovascular and cerebrovascular diseases. Monitoring trends of cholesterol levels and comparing trends across population groups are important to assess population distribution and risks related to cholesterol change over time. Cholesterol surveillance data are lacking, even in high-income countries. Objectives To describe the trends in cholesterol and triglyceride levels in different population groups and to estimate the risk of developing hypercholesterolemia and hypertriglyceridemia in Västerbotten County, Sweden during 1990–2010. Designs and Methods Since 1990, 133,082 individuals living in Västerbotten County, Northern Sweden, invited on their 30th, 40th, 50th and 60th birthdays, participated in the Västerbotten Intervention Program. Ten years after baseline data collection, 34,868 individuals were surveyed for a second time. In addition to a self-administered health questionnaire (that included information on socioeconomic status, demographics, self-reported health and lifestyle behaviours), blood cholesterol and triglyceride were examined. Results The level and prevalence of hypercholesterolemia decreased significantly from 1990 to 2007, but the trends began to increase during 2008–2010 in men, women, and in all educational groups. Men had significantly higher serum triglyceride levels than women and their cholesterol levels were similar to those of the women. This study shows that those with basic education and who live in rural inlands had consistently higher triglyceride level than those who live in the city and have higher educational attainments. People with basic education are also at higher risk of developing hypercholesterolemia and hypertriglyceridemia at 10-year follow-up; the risk is much higher among the older cohorts, particularly women. During 1990–2010, the proportion of participants who reported treatment with lipid

  16. Mung bean decreases plasma cholesterol by up-regulation of CYP7A1.

    Science.gov (United States)

    Yao, Yang; Hao, Liu; Shi, Zhenxing; Wang, Lixia; Cheng, Xuzhen; Wang, Suhua; Ren, Guixing

    2014-06-01

    Our results affirmed that supplementation of 1 or 2% mung bean could decrease plasma total cholesterol and triacylglycerol level. Mung bean increased mRNA 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Most importantly, mung bean increased not only the protein level of cholesterol-7α-hydroxylase (CYP7A1) but also mRNA CYP7A1. It was concluded that the hypocholesterolemic activity of mung bean was most probable mediated by enhancement of bile acid excretion and up-regulation of CYP7A1.

  17. Serum triglycerides, but not cholesterol or leptin, are decreased in suicide attempters with mood disorders.

    Science.gov (United States)

    da Graça Cantarelli, Maria; Nardin, Patrícia; Buffon, Andréia; Eidt, Murilo Castilhos; Antônio Godoy, Luiz; Fernandes, Brisa S; Gonçalves, Carlos-Alberto

    2015-02-01

    Many peripheral biomarkers, including low cholesterol and its fractions, have been examined to identify suicidal behavior. Herein, we assessed serum lipid profile and some proteins putatively associated with suicidal behavior in subjects with mood disorder (bipolar disorder or major depressive disorder) with a recent suicide attempt and with no lifetime history of suicide attempts. Fifty subjects had presented an episode of attempted suicide during the last 15 days, and 36 subjects had no history of any suicide attempt. We measured total cholesterol, HDL, LDL and triglycerides as well as serum leptin, brain-derived neurotrophic factor (BDNF), S100B and C-reactive protein (CRP). Individuals that had attempted suicide presented decreased body mass index (BMI) and waist circumference. After adjusting for these confounders, we found that triglycerides were decreased in attempted suicide subjects. We found no differences among total cholesterol, LDL, and HDL or leptin, S100B, CRP and BDNF. This is a cross-sectional study, and we cannot therefore assess whether a decrease in triglycerides caused a mood episode with suicidal ideation that led to a suicide attempt or if the presence of a mood episode originated a loss of appetite and consequent loss of weight, therefore decreasing triglyceride levels. These results do not support the hypothesis that lower levels of cholesterol are associated with suicidal behavior in a mood disorder sample. However, our data support the idea that adiposity is differentiated in these patients (reduced BMI, waist circumference and serum triglycerides), which could lead to an altered communication between the adipose tissue and brain. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL support TICE, antisense oligonucleotides (ASO were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP, which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg mice, which predominantly excrete cholesterol via TICE, and wild type (WT littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  19. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Science.gov (United States)

    Marshall, Stephanie M; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; McDaniel, Allison L; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

    2014-01-01

    An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  20. Fish oil increases atherosclerosis and hepatic steatosis, although decreases serum cholesterol in Wistar rat

    Directory of Open Access Journals (Sweden)

    Minoo M-Shirazi

    2011-01-01

    Full Text Available Background: It is known that fish oil consumption decreases incidence of cardiovascular disease. However, some studies showed that it increases atherosclerosis as it does not get completely metabolized by the liver. The aim of the present study was to investigate the effects of fish oil on aortic atherosclerosis, hepatic steatosis and serum lipids in rats. Methods: Twenty pregnant Wistar rats were fed with a fish oil-containing diet or standard diet (containing soy bean oil during pregnancy and lactation and the pups were weaned onto the same diet. Fasting blood samples, hepatic and aortic specimens were taken from pups on day 70 postnatal. Data were analyzed with SPSS software, using t-test, Mann-Whitney test and Spearman correlation coefficient. Values of p < 0.05 were considered significant. Results: Medians for fatty streak in aorta of fish oil fed and soy bean oil fed pups were 1.00 and 0.00, respectively, and P value was 0.042. Also, medians for ductular cell hyperplasia of liver in fish oil fed and soy bean oil fed pups were 1.00 and 0.00, respectively, and P value was 0.014. Total cholesterol in pups fed with fish oil was 52.20 mg/dl and in pups fed with soy bean oil was 83.90 mg/dl (p < 0.00 and for low density lipoprotein cholesterol (LDL-C values were 8.79 mg/dl and 13.16 mg/dl, respectively (p = 0.031. Conclusions: According to the results of the present study, a diet which provided 15.9% of energy from fish oil as the only source of dietary fat, induced aortic atherosclerosis as well as hepatic steatosis in Wistar rat, although it decreased total cholesterol and LDL-C.

  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. Cholesterol pathways affected by small molecules that decrease sterol levels in Niemann-Pick type C mutant cells.

    Directory of Open Access Journals (Sweden)

    Madalina Rujoi

    Full Text Available BACKGROUND: Niemann-Pick type C (NPC disease is a genetically inherited multi-lipid storage disorder with impaired efflux of cholesterol from lysosomal storage organelles. METHODOLOGY/PRINCIPAL FINDINGS: The effect of screen-selected cholesterol lowering compounds on the major sterol pathways was studied in CT60 mutant CHO cells lacking NPC1 protein. Each of the selected chemicals decreases cholesterol in the lysosomal storage organelles of NPC1 mutant cells through one or more of the following mechanisms: increased cholesterol efflux from the cell, decreased uptake of low-density lipoproteins, and/or increased levels of cholesteryl esters. Several chemicals promote efflux of cholesterol to extracellular acceptors in both non-NPC and NPC1 mutant cells. The uptake of low-density lipoprotein-derived cholesterol is inhibited by some of the studied compounds. CONCLUSIONS/SIGNIFICANCE: Results herein provide the information for prioritized further studies in identifying molecular targets of the chemicals. This approach proved successful in the identification of seven chemicals as novel inhibitors of lysosomal acid lipase (Rosenbaum et al, Biochim. Biophys. Acta. 2009, 1791:1155-1165.

  3. 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.

  4. LECITHIN: CHOLESTEROL ACYLTRANSFERASE ACTIVITY IS DECREASED IN TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    A. Ghanei

    2007-09-01

    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a major role in the removal of free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the main indicator of HDL-C function. The aim of the study was to measure LCAT activity in type 2 diabetic patients and to elucidate whether LCAT is associated with metabolic control, and insulin resistance. A case-control study was conducted in Imam Khomeini Hospital during 2006, recruiting 45 type 2 diabetes mellitus patients and 45 healthy subjects. Cases and controls were matched regarding gender, age and body mass index (BMI. FBS, lipid profile, LCAT activity, HbA1C, insulin were measured and insulin resistance (HOMA-IRwas calculated for both patients and controls. The studied variables were then compared between the two groups, and the association of LCAT activity with any of the variables was examined. Twenty-five subjects were female and 20 male both among patients and controls. Mean age of diabetics was 49.9 yrs (range, 40-64, and of controls 51.1 yrs (range, 39-64. FBS, HbA1C, HOMA-IR and TG in patients were significantly higher than controls, and HDL-C in controls was significantly higher than patients. LCAT activity of patients (73 9.1 µmol/L/h was significantly lower than that in controls (88 4.5 µmol/L/h (p<0.001. LCAT activity had significant inverse correlations with HbA1C and duration of diabetes. After multilinear regression analysis in patients, LCAT activity was only correlated with HbA1C level (ß= -0.9, p<0.001. LCAT activity had no significant association with HDL-C and HOMA-IR in any of the groups."nLCAT activity is significantly decreased in patients with type 2 diabetes compared with healthy controls, and has an inverse correlation with the magnitude of hyperglycemia.

  5. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin.

    Science.gov (United States)

    Krikken, J A; Waanders, F; Dallinga-Thie, G M; Dikkeschei, L D; Vogt, L; Navis, G J; Dullaart, R P F

    2009-05-01

    Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) mass and whether changes in HDL-C were related to changes in plasma adiponectin. Thirty-two non-diabetic proteinuric patients (12 on statin therapy), were followed during two double blind 6-week periods of placebo and treatment (low sodium + 100mg losartan + 25 mg hydrochlorothiazide). With placebo HDL-C was lower but LDL-C and CETP were not different in proteinuric patients compared with matched controls. LDL-C, HDL-C and CETP decreased upon proteinuria reduction. The decrease in LDL-C correlated with the drop in CETP and the degree of proteinuria reduction. HDL-C also decreased in proportion to proteinuria lowering. Individual changes in HDL-C were correlated with changes in adiponectin. LDL-C lowering upon robust reduction of proteinuria may be affected by changes in plasma CETP mass, but this treatment also decreases HDL-C in relation to the degree of proteinuria reduction. This adverse effect on HDL-C may in part be attributable to changes in adiponectin.

  6. Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster.

    Science.gov (United States)

    Pitha, J; Bobková, D; Kovár, J; Havlícková, J; Poledne, R

    2010-01-01

    The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n = 5), ovariectomized animals (n = 9), ovariectomized animals treated for 12 weeks (n = 10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n = 9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol.

  7. 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...

  8. 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

    echocardiographic measures in a population of patients with type 2 diabetes. METHODS: Comprehensive echocardiography including 2D-speckle tracking echocardiography was performed on a representative sample of 924 patients with type 2 diabetes-730 of whom were treated with statins. These were recruited from two large...... 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...

  9. Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro.

    Science.gov (United States)

    Rung, Emilia; Friberg, P Anders; Shao, Ruijin; Larsson, D G Joakim; Nielsen, Eva Ch; Svensson, Per-Arne; Carlsson, Björn; Carlsson, Lena M S; Billig, Håkan

    2005-03-01

    Progesterone-receptor (PR) stimulation promotes survival in rat and human periovulatory granulosa cells. To investigate the mechanisms involved, periovulatory rat granulosa cells were incubated in vitro with or without the PR-antagonist Org 31710. Org 31710 caused the expected increase in apoptosis, and expression profiling using cDNA microarray analysis revealed regulation of several groups of genes with functional and/or metabolic connections. This regulation included decreased expression of genes involved in follicular rupture, increased stress responses, decreased angiogenesis, and decreased cholesterol synthesis. A decreased cholesterol synthesis was verified in experiments with both rat and human periovulatory granulosa cells treated with the PR-antagonists Org 31710 or RU 486 by measuring incorporation of [14C]acetate into cholesterol, cholesterol ester, and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory rat granulosa cells using 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (lovastatin, mevastatin, or simvastatin) increased apoptosis, measured as DNA fragmentation and caspase-3/7 activity. The increase in apoptosis caused by simvastatin was reversed by addition of the cholesterol synthesis-intermediary mevalonic acid. These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival.

  10. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Maurilio da Silva Morrone

    2016-01-01

    Full Text Available The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n=8 and one OVX group (n=11 were treated with vehicle (refined olive oil, and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n=8/group. OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause.

  11. Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats.

    Science.gov (United States)

    Morrone, Maurilio da Silva; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; da Boit Martinello, Katia; Saldanha Henkin, Bernardo; Rabello, Thallita Kelly; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-01-01

    The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause.

  12. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    J.A. Krikken; F. Waanders; G.M. Dallinga-Thie; L.D. Dikkeschei; L. Vogt; G.J. Navis; R.P.F. Dullaart

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  13. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients : relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    Krikken, J. A.; Waanders, F.; Dallinga-Thie, G. M.; Dikkeschei, L. D.; Vogt, L.; Navis, G. J.; Dullaart, R. P. F.

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  14. Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate

    Directory of Open Access Journals (Sweden)

    Koji Matsuo

    2015-08-01

    Full Text Available One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS, a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6% and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.

  15. Cholesterol-lowering effect of beta-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when beta-glucan is incorporated into bread and cookies

    NARCIS (Netherlands)

    Kerckhoffs, D.A.J.M.; Hornstra, G.; Mensink, R.P.

    2003-01-01

    Cholesterol-lowering effect of beta-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when beta-glucan is incorporated into bread and cookies. Kerckhoffs DA, Hornstra G, Mensink RP. Department of Human Biology, Maastricht University, Maastricht, The Netherlands. BACKGROUND: F

  16. Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats:possible role of decreased lecithin cholesterol acetyl transferase activity

    Institute of Scientific and Technical Information of China (English)

    VR Santhosh Kumar; Md Naseeruddin Inamdar; Nayeemunnisa; GL Viswanatha

    2011-01-01

    Objective:To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats.Methods: Administration of dexamethasone was given at10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index.Results: Lemongrass oil (100and200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin10mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase(LCAT) activity.Conclusions: These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity.

  17. Correlation between the decrease of cholesterol efflux from macrophages in patients with type II diabetes mellitus and down-regulated CYP7A1 expression.

    Science.gov (United States)

    Bao, L D; Li, C Q; Peng, R; Ren, X H; Ma, R L; Wang, Y; Lv, H J

    2015-07-31

    The purpose of this study was to examine the changes of cellular cholesterol efflux from macrophages in patients with type II diabetes mellitus (DM), and to determine the expression of CYP7A1, ABCG5, and LXRβ therein. We recruited 30 patients with type II DM (including 15 patients complicated with coronary heart disease and 15 patients with DM only) and 15 normal controls for this study. Peripheral blood monocytes were isolated for macrophage culture. The mRNA and protein expression levels of CYP7A1, ABCG5, and LXRβ were determined using real-time polymerase chain reaction and western blot. The macrophage cholesterol efflux rate was determined with 10% autoserum and standard serum as receptors. We determined that the expression levels of macrophage CYP7A1 mRNA and protein in the type II DM group were significantly lower than those in the control group, but no differences were found in the ABCG5 and LXRβ expression levels between the groups. The macrophage cholesterol efflux rate in the patients with type II DM was also significantly decreased compared with that of the normal control subjects (P CYP7A1 mRNA expression and macrophage cholesterol efflux rate were significantly positively correlated. In summary, this study demonstrated that the macrophage cholesterol efflux in patients with type II DM was significantly reduced, and that this reduction was associated with the down-regulation of CYP7A1 expression.

  18. Decreased heart rate variability in HIV positive patients receiving antiretroviral therapy: importance of blood glucose and cholesterol.

    Directory of Open Access Journals (Sweden)

    Gro Askgaard

    Full Text Available UNLABELLED: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Antiretroviral combination therapy (ART has dramatically changed the course of the disease and improved prognosis and decreased morbidity. AIM: To evaluate whether autonomic dysfunction is present in an ART treated HIV population and if so to identify factors of importance. METHODS: HIV patients receiving ART for at least 12 months (n = 97 and an age-matched control group of healthy volunteers (n = 52 were included. All were non-diabetic and had never received medication for hypertension. Following a 10 min resting period a 15 min ECG recording was performed. Heart-rate variability (HRV analysis was performed in accordance with current guidelines and data reported as mean [interquartile range]. RESULTS: Mean normal-to-normal (NN and total HRV measured as standard deviation of normal-to-normal (SDNN was lower in HIV patients compared to controls (905 vs. 982 ms; p<0.001 and 48 vs. 54 ms; p = 0.028, respectively. No differences were found between the groups in parasympathetic activity measured as square root of the mean squared difference of successive NN-intervals (RMSSD or the percent of differences between adjacent NN intervals greater than 50 ms (pNN50. In the HIV positives, haemoglobin A1c correlated inversely with SDNN, RMSSD and pNN50 (p<0.05. Total cholesterol and LDL-C correlated inversely with RMSSD and pNN50 (p<0.05. Neither HIV duration, HIV-RNA, CD4 cell count nor CD4 nadir correlated with time or phase domain HRV variables. CONCLUSIONS: Moderate autonomic dysfunction is present in HIV positives patients even with suppressed viral load due to ART. The dysfunction is correlated with HbA1c and hypercholesterolemia but not to duration of HIV or whether the patients were receiving protease inhibitors as part of the ART regime.

  19. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice.

    Science.gov (United States)

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Weller, Curtis L; Carr, Timothy P; Park, Young-Ki; Lee, Ji-Young

    2015-11-01

    We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively.

  20. Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling

    Science.gov (United States)

    Urlep, Žiga; Lorbek, Gregor; Perše, Martina; Jeruc, Jera; Juvan, Peter; Matz-Soja, Madlen; Gebhardt, Rolf; Björkhem, Ingemar; Hall, Jason A.; Bonneau, Richard; Littman, Dan R.; Rozman, Damjana

    2017-01-01

    Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (HCyp51‑/‑) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption. Further evidence for this comes from the global analysis that identified a crucial overlap between hepatic Cyp51‑/‑ and Rorc‑/‑ expression profiles. Additionally, the reduction in RORA and RORC transcriptional activity was greater in adult HCyp51‑/‑ females than males, which correlates well with their downregulated amino and fatty acid metabolism. Overall, we identify a global and sex-dependent transcriptional de-regulation due to the block in cholesterol synthesis during development of the Cyp51 knockout mice and provide in vivo evidence that sterol intermediates downstream of lanosterol may regulate the hepatic RORC activity.

  1. Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression: evidence for a farnesoid-X-receptor mechanism of action.

    Science.gov (United States)

    Zhang, Jun; Kris-Etherton, Penny M; Thompson, Jerry T; Hannon, Daniel B; Gillies, Peter J; Heuvel, John P Vanden

    2012-04-01

    Increased cholesterol efflux from macrophage-derived foam cells (MDFCs) is an important protective mechanism to decrease lipid load in the atherosclerotic plaque. Dietary alpha-linolenic acid (ALA), an omega-3 polyunsaturated fatty acid (PUFA), decreases circulating cholesterol, but its role in cholesterol efflux has not been extensively studied. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids (MUFAs). Endogenous MUFAs are preferentially incorporated into triglycerides, phospholipids and cholesteryl ester, which are abundant in atherosclerotic plaque. This study investigated the mechanisms by which ALA regulated SCD1 and subsequent effect on cholesterol storage and transport in MDFCs. Small interfering RNA (siRNA) also was applied to modify SCD1 expression in foam cells. Alpha-linolenic acid treatment and SCD1 siRNA significantly decreased SCD1 expression in MDFCs. The reduction of SCD1 was accompanied with increased cholesterol efflux and decreased intracellular cholesterol storage within these cells. Alpha-linolenic acid activated the nuclear receptor farnesoid-X-receptor, which in turn increased its target gene small heterodimer partner (SHP) expression, and decreased liver-X-receptor dependent sterol regulatory element binding protein 1c transcription, ultimately resulting in repressed SCD1 expression. In conclusion, repression of SCD1 by ALA favorably increased cholesterol efflux and decreased cholesterol accumulation in foam cells. This may be one mechanism by which dietary omega-3 PUFAs promote atherosclerosis regression. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting.

    Science.gov (United States)

    Hasvold, Pål; Thuresson, Marcus; Sundström, Johan; Hammar, Niklas; Kjeldsen, Sverre E; Johansson, Gunnar; Holme, Ingar; Bodegård, Johan

    2016-03-01

    Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased ≥0.1 mmol/L, unchanged ±0.1 or ≥0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. HDL-C decreased in 20%, was unchanged in 58%, and increased in 22% of patients initiated on statin treatment (96% treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56% higher MACE risk (hazard ratio 1.56; 95% confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.

  3. 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

    • Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

      Directory of Open Access Journals (Sweden)

      Si-Yuan Pan

      2011-01-01

      Full Text Available Effects of the ethanol extract of Fructus Schisandrae (EtFSC on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC levels (up to 62% and 165%, resp. and hepatic triglyceride (TG levels (up to 528% in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g. significantly decreased the hepatic TG level (down to 35% and slightly increased the hepatic index (by 8% in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g. significantly lowered the hepatic TG level (by 61%, it elevated the hepatic index (by 77% in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment.

    • 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 , ...

    • 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- ...

    • 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- ...

    • L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP.

      Science.gov (United States)

      Gao, Na; Qu, Xia; Yan, Jin; Huang, Qi; Yuan, Hao-Yong; Ouyang, Dong-Sheng

      2010-12-01

      Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

    • A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

      NARCIS (Netherlands)

      De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF

      2005-01-01

      The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

    • Short-term Acipimox decreases the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux : a potentially adverse effect on reverse cholesterol transport

      NARCIS (Netherlands)

      Dullaart, RPF; van Tol, A

      Aims To evaluate the effect of short-term administration of the anti-lipolytic agent, Acipimox, on the ability of plasma to stimulate cellular cholesterol removal, which represents one of the first steps in the anti-atherogenic process of reverse cholesterol transport. Methods Eight male Type 2

    • Short-term Acipimox decreases the ability of plasma from type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux: A potentially adverse effect on reverse cholesterol transport

      NARCIS (Netherlands)

      R.P.F. Dullaart (Robin); A. van Tol (Arie)

      2001-01-01

      textabstractAims: To evaluate the effect of short-term administration of the anti-lipolytic agent, Acipimox, on the ability of plasma to stimulate cellular cholesterol removal, which represents one of the first steps in the anti-atherogenic process of reverse cholesterol transport. Methods: Eight

    • A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

      NARCIS (Netherlands)

      De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF

      2005-01-01

      The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

    • Use of Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry to Demonstrate Decreased Serum Statin Levels after Extracorporeal LDL-Cholesterol Elimination

      Directory of Open Access Journals (Sweden)

      M. Bláha

      2011-01-01

      Full Text Available Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites after extracorporeal LDL-cholesterol elimination (EE in severe familial hypercholesterolemia (FH. The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3–12 years of treatment with severe FH (12 patients and treated regularly by LDL-apheresis (immunoadsorption or haemorheopheresis (cascade filtration were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l. A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters. To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours. Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.

    • Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum.

      Science.gov (United States)

      Yang, Peng-Yuan; Almofti, Mohamad Radwan; Lu, Ling; Kang, Hui; Zhang, Jing; Li, Tie-Jun; Rui, Yao-Cheng; Sun, Lian-Na; Chen, Wan-Sheng

      2005-11-01

      Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of Polygonum multiflorum Thunb., one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg). Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF) protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.

    • 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 ...

    • Cholesterol Levels

      Science.gov (United States)

      ... this page: https://medlineplus.gov/labtests/cholesterollevels.html Cholesterol Levels To use the sharing features on this page, please enable JavaScript. What is a Cholesterol Test? Cholesterol is a waxy, fat-like substance ...

    • Hepatic Deletion of SIRT1 Decreases Hepatocyte Nuclear Factor 1α/Farnesoid X Receptor Signaling and Induces Formation of Cholesterol Gallstones in Mice

      Science.gov (United States)

      Purushotham, Aparna; Xu, Qing; Lu, Jing; Foley, Julie F.; Yan, Xingjian; Kim, Dong-Hyun; Kemper, Jongsook Kim

      2012-01-01

      SIRT1, a highly conserved NAD+-dependent protein deacetylase, is a key metabolic sensor that directly links nutrient signals to animal metabolic homeostasis. Although SIRT1 has been implicated in a number of hepatic metabolic processes, the mechanisms by which hepatic SIRT1 modulates bile acid metabolism are still not well understood. Here we report that deletion of hepatic SIRT1 reduces the expression of farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid homeostasis. We provide evidence that SIRT1 regulates the expression of FXR through hepatocyte nuclear factor 1α (HNF1α). SIRT1 deficiency in hepatocytes leads to decreased binding of HNF1α to the FXR promoter. Furthermore, we show that hepatocyte-specific deletion of SIRT1 leads to derangements in bile acid metabolism, predisposing the mice to development of cholesterol gallstones on a lithogenic diet. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of hepatic bile acid homeostasis through the HNF1α/FXR signaling pathway. PMID:22290433

    • Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography.

      Science.gov (United States)

      Kanda, Eiichiro; Ai, Masumi; Iwamoto, Asami; Okazaki, Mitsuyo; Maeda, Yoshitaka; Sasaki, Sei; Yoshida, Masayuki

      2013-10-26

      Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin.

    • Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of the rate-limiting enzyme of cholesterol synthesis in a chronic mouse model of depression.

      Science.gov (United States)

      Wang, Junhui; Qiao, Jinping; Zhang, Yanbo; Wang, Hongxing; Zhu, Shenghua; Zhang, Handi; Hartle, Kelly; Guo, Huining; Guo, Wei; He, Jue; Kong, Jiming; Huang, Qingjun; Li, Xin-Min

      2014-10-01

      Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it takes 2-3 weeks for the mood-enhancing effects, which indicate other mechanisms may underlie their treatment effects. Here, we investigated the role of white matter in treatment and pathogenesis of depression using an unpredictable chronic mild stress (UCMS) mouse model. Desvenlafaxine (DVS) was orally administrated to UCMS mice at the dose of 10 mg/kg/day 1 week before they went through a 7-week stress procedure and lasted for over 8 weeks before the mice were killed. No significant changes were found for protein markers of neurons and astrocytes in UCMS mice. However, myelin and oligodendrocyte-related proteins were significantly reduced in UCMS mice. DVS prevented the stress-induced injury to white matter and the decrease of phosphorylated 5'-AMP-activated protein kinase and 3-hydroxy-3-methyl-glutaryl-CoA reductase protein expression. DVS increased open arm entries in an elevated plus-maze test, sucrose consumption in the sucrose preference test and decreased immobility in tail suspension and forced swimming tests. These findings suggest that stress induces depression-like behaviors and white matter deficits in UCMS mice. DVS may ameliorate the oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the depression-like phenotypes in these mice. We examined the possible role of oligodendrocyte and myelin in the pathological changes of depression with an unpredictable chronic mild stress (UCMS) mouse model. Oligodendrocyte-related proteins in the mouse brain were specifically changed during the stress period. The depressive-like behaviors and oligodendrocyte deficits could be prevented by the administration of desvenlafaxine. Oligodendrocyte and myelin may be an essential target of desvenlafaxine for the treatment of depression. © 2014 International Society for Neurochemistry.

    • Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

      NARCIS (Netherlands)

      Dullaart, RPF; Riemens, SC; Scheek, LM; van Tol, A

      1999-01-01

      Background Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods The effects of exogenous hyperinsulinaemia on plasma

  1. Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

    NARCIS (Netherlands)

    R.P.F. Dullaart (Robin); S.C. Riemens; L. Scheek (Leo); A. van Tol (Arie)

    1999-01-01

    textabstractBackground. Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods. The effects of exogenous

  2. Nori- and sea spaghetti- but not wakame-restructured pork decrease the hypercholesterolemic and liver proapototic short-term effects of high-dietary cholesterol consumption.

    Science.gov (United States)

    Schultz Moreira, Adriana R; Benedi, Juana; Bastida, Sara; Sánchez-Reus, Isabel; Sánchez-Muniz, Francisco J

    2013-01-01

    Restructured pork (RP) enriched in Seaweeds are potential functional foods. The antiapoptotic and hypocholesterolemic effects of consuming cholesterol enriched diets containing Wakame-RP (CW), Nori-RP (CN) and Sea Spaghetti (CS) were tested in a 1-wk study. Groups of six rats per group were fed a mix of 85% AIN-93M rodent-diet containing cholesterol and cholic acid as a cholesterol rising agent plus 15% RP containing alga. These diets were compared to control-RP diets enriched or not in cholesterol (CC and C, respectively). After 1-wk, cholesterol feeding significantly increased liver apoptosis markers which were significantly reduced by CS (cellular cycle DNA, caspase-3, and cytochrome c), CN (caspase-3 and cytochrome c) and CW (caspase-3) diets. CN and CS diets significantly blocked the cholesterolaemic rising effect observed in the CC group but no protective effect was observed in the CW group. Differences in seaweed composition added to RP appear responsible for blocking or not the proapoptotic and hypercholesterolemic effects of high cholesterol-RP consumption; thus, any generalization on seaweed effects or food containing seaweeds must be avoided. Although present results are worthy, future studies are demanded to ascertain the utility of consuming algal-RP as part of usual diets.

  3. Nori- and Sea Spaghetti- but not Wakame-restructured pork decrease the hypercholesterolemic and liver proapototic short-term effects of high-dietary cholesterol consumption

    Directory of Open Access Journals (Sweden)

    Adriana R. Schultz Moreira

    2013-10-01

    Full Text Available Restructured pork (RP enriched in Seaweeds are potential functional foods. The antiapoptotic and hypocholesterolemic effects of consuming cholesterol enriched diets containing Wakame-RP (CW, Nori-RP (CN and Sea Spaghetti (CS were tested in a 1-wk study. Groups of six rats per group were fed a mix of 85% AIN-93M rodent-diet containing cholesterol and cholic acid as a cholesterol rising agent plus 15% RP containing alga. These diets were compared to control-RP diets enriched or not in cholesterol (CC and C, respectively. After 1-wk, cholesterol feeding significantly increased liver apoptosis markers which were significantly reduced by CS (cellular cycle DNA, caspase-3, and cytochrome c, CN (caspase-3 and cytochrome c and CW (caspase-3 diets. CN and CS diets significantly blocked the cholesterolaemic rising effect observed in the CC group but no protective effect was observed in the CW group. Differences in seaweed composition added to RP appear responsible for blocking or not the proapoptotic and hypercholesterolemic effects of high cholesterol-RP consumption; thus, any generalization on seaweed effects or food containing seaweeds must be avoided. Although present results are worthy, future studies are demanded to ascertain the utility of consuming algal-RP as part of usual diets.

  4. Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol.

    Science.gov (United States)

    Gumral, Nurhan; Kumbul, Duygu Doguc; Aylak, Firdevs; Saygin, Mustafa; Savik, Emin

    2015-01-01

    It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250-300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant-antioxidant effect in the heart tissue of rats. © The Author(s) 2012.

  5. Activity assay of mangosteen (Garcinia mangostana L.) pericarp extract for decreasing fasting blood cholesterol level and lipid peroxidation in type-2 diabetic mice

    Science.gov (United States)

    Husen, Saikhu Akhmad; Winarni, Dwi; Khaleyla, Firas; Kalqutny, Septian Hary; Ansori, Arif Nur Muhammad

    2017-09-01

    This study aimed to explore the activity of pericarp extract of mangosteen (Garcinia mangostana L.). Mangosteen pericarp contains various active compounds which are beneficial for human health. In-vivo antioxidant assay of pericarp extract was carried out using 3-4 month male mice of strain BALB/c weighed 30-40 g. The mice were divided into two groups: normal control (KN) group and STZ-induced diabetic group. STZ induction was performed using multiple low-dose method 30 mg/kg body weight treated daily for five consecutive days. Diabetic group was separated into two subgroups: diabetic control (KD), metformin control (KM), and crude extract treatment subgroups. The fasting blood glucose and the cholesterol level were measured before and after lard treatment, we also did it on the first, seventh, and fourteenth day of mangosteen pericarp crude extract treatment. The mice were treated with mangosteen pericarp crude extract for 14 days. The MDA level of the fasting blood serum was measured. The body weight and fasting blood cholesterol level before and after lard treatment were analyzed by t-test, whereas, the fasting blood cholesterol and the MDA level were analyzed using one-way variant analysis continued with Duncan test. The correlation between the increasing body weight and the fasting blood cholesterol level was determined by Pearson correlation test. The results of the study showed that the administration of mangosteen pericarp crude extract was able to reduce the fasting blood cholesterol and the malondialdehide level significantly.

  6. 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 ...

  7. Carotenoids, birdsong and oxidative status: administration of dietary lutein is associated with an increase in song rate and circulating antioxidants (albumin and cholesterol and a decrease in oxidative damage.

    Directory of Open Access Journals (Sweden)

    Stefania Casagrande

    Full Text Available Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites, we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits.

  8. Carotenoids, birdsong and oxidative status: administration of dietary lutein is associated with an increase in song rate and circulating antioxidants (albumin and cholesterol) and a decrease in oxidative damage.

    Science.gov (United States)

    Casagrande, Stefania; Pinxten, Rianne; Zaid, Erika; Eens, Marcel

    2014-01-01

    Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris) fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites), we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits.

  9. Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils.

    Science.gov (United States)

    Wasan, K M; Najafi, S; Wong, J; Kwong, M; Pritchard, P H

    2001-01-01

    The purpose of this project was to determine the effect of a FM-VP4 when incorporated into the diet or drinking water on plasma lipids, body weight, and hepatic and renal function following chronic oral administration to gerbils. Gerbils were administered water and food daily containing either no FM-VP4 (controls; n=6), 2% or 4% FM-VP4 incorporated into the gerbil diet (n=6 each treatment group) or 2% or 4% FM-VP4 dissolved in the drinking water (n=6 each treatment group). Body weight and food and water intake were monitored weekly. Following 8 weeks of this regiment blood was obtained via a cardiac puncture and all animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride and high-density lipoprotein (HDL)-cholesterol levels by standard enzymatic and precipitation techniques. Low-density lipoprotein (LDL)-cholesterol levels were determined by the Friedewald equation. The plasma was also analyzed for changes in hepatic enzyme (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and plasma creatinine (renal function) concentrations. 2% and 4% FM-VP4 administration incorporated both into the diet and in the drinking water resulted in a significant decrease in total plasma cholesterol and LDL cholesterol concentration compared to controls. Animals administered 4% FM-VP4 in either their diet or drinking water had significantly lower body weight following the 8 weeks of treatment compared to the other groups. Significant differences in daily water intake was observed in all treatment groups with the exception of the 2% FM-VP4 in diet group compared to controls. Significant differences in daily food intake were observed in gerbils administered 2% FM-VP4 in the drinking water and 4% FM-VP4 in the diet and drinking water groups compared to controls. A significant decrease in total plasma triglyceride concentration was observed in gerbils administered 4% FM-VP4 in their drinking water compared

  10. Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function, are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα.

    Science.gov (United States)

    Lomax, Michael A; Karamanlidis, Georgios; Laws, John; Cremers, Stephanie G; Weinberg, Peter D; Clarke, Lynne

    2013-04-01

    The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.

  11. 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 ...

  12. Cholesterol and Women's Health

    Science.gov (United States)

    ... cholesterol.” What is dyslipidemia? Having abnormal levels of cholesterol or triglycerides is called dyslipidemia . A common dyslipidemia in the ... the levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. When should my cholesterol levels be measured? Women ...

  13. 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 ...

  14. 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...

  15. High Blood Cholesterol

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Cholesterol? To understand high blood cholesterol (ko-LES-ter- ... cholesterol from your body. What Is High Blood Cholesterol? High blood cholesterol is a condition in which ...

  16. New Cholesterol Fighting Meds Target Key Gene

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_165942.html New Cholesterol Fighting Meds Target Key Gene Two trials show ... New gene-based therapies appear to significantly decrease cholesterol levels in people, and could even cut down ...

  17. Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins.

    Science.gov (United States)

    El Harchaoui, Karim; Akdim, Fatima; Stroes, Erik S G; Trip, Mieke D; Kastelein, John J P

    2008-01-01

    Low-density lipoprotein-cholesterol (LDL-C) lowering is the mainstay of the current treatment guidelines in the management of cardiovascular risk. HMG-CoA reductase inhibitors (statins) are currently the most effective LDL-C-lowering drugs. However, a substantial number of patients do not reach treatment targets with statins. Therefore, an unmet medical need exists for lipid-lowering drugs with novel mechanisms of action to reach the recommended cholesterol target levels, either by monotherapy or combination therapy. Upregulation of the LDL receptor with squalene synthase inhibitors has shown promising results in animal studies but the clinical development of the lead compound lapaquistat (TAK-475) has recently been discontinued. Ezetimibe combined with statins allowed significantly more patients to reach their LDL-C targets. Other inhibitors of intestinal cholesterol absorption such as disodium ascorbyl phytostanol phosphate (FM-VP4) and bile acid transport inhibitors have shown positive results in early development trials, whereas the prospect of acyl coenzyme A: cholesterol acyltransferase inhibition in cardiovascular prevention is dire. Selective inhibition of messenger RNA (mRNA) by antisense oligonucleotides is a new approach to modify cholesterol levels. The inhibition of apolipoprotein B mRNA is in advanced development and mipomersen sodium (ISIS 301012) has shown striking results in phase II studies both as monotherapy as well as in combination with statins.

  18. Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults.

    Science.gov (United States)

    Price, Ruth K; Keaveney, Edel M; Hamill, Lesley L; Wallace, Julie M W; Ward, Mary; Ueland, Per M; McNulty, Helene; Strain, J J; Parker, Michael J; Welch, Robert W

    2010-12-01

    There is strong evidence that whole-grain foods protect against heart disease. Although underlying mechanisms and components are unclear, betaine, found at high levels in wheat aleurone, may play a role. We evaluated the effects of a diet high in wheat aleurone on plasma betaine and related measures. In a parallel, single-blinded intervention study, 79 healthy participants (aged 45-65 y, BMI ≥ 25 kg/m(2)) incorporated either aleurone-rich cereal products (27 g/d aleurone) or control products balanced for fiber and macronutrients into their habitual diets for 4 wk. Fasting blood samples were taken at baseline and postintervention (4 wk) from participants. Compared with the control, the aleurone products provided an additional 279 mg/d betaine and resulted in higher plasma betaine (P aleurone-rich products into the habitual diet for 4 wk significantly increases plasma betaine concentrations and lowers tHcy, which is attributable to enhanced betaine-homocysteine methyltransferase-mediated remethylation of homocysteine. Although this supports a role for betaine in the protective effects of whole grains, concomitant decreases in LDL suggest more than one component or mechanism may be responsible.

  19. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    Science.gov (United States)

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

  20. 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 ...

  1. HDL Cholesterol Test

    Science.gov (United States)

    ... 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 ; ...

  2. Cholesterol IQ Quiz

    Science.gov (United States)

    ... 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 ...

  3. 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 ...

  4. Lifestyle Changes and Cholesterol

    Science.gov (United States)

    ... 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 ...

  5. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... 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 ...

  6. A review of clinical trials in dietary interventions to decrease the incidence of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Miettinen Tatu A

    2001-04-01

    Full Text Available Abstract Of the associations between dietary elements and coronary artery disease (CAD, the greatest body of evidence deals with the beneficial effect of reducing the dietary intake of saturated fatty acids and cholesterol. Furthermore, it is well established, on the basis of convincing evidence, that reduction in serum total cholesterol results in reduction in coronary morbidity and mortality, as well as in regression of other atherosclerotic manifestations.In fact, dietary intervention studies revealed that it is possible to reduce the incidence of coronary death and nonfatal myocardial infarction, as well as manifestations of atherosclerosis in cerebral and peripheral arteries, by reducing dietary intake of saturated fat and cholesterol. In two recently reported dietary interventions the incidence of coronary events, especially coronary mortality, and total mortality were reduced by increased intake of n-3 long-chain polyunsaturated fatty acids and by a modification of the diet toward a Mediterranean-type diet (rich in α-linolenic acid. In addition to those findings, the potential efficacy of the dietary newcomers phytostanol and phytosterol esters on reducing coronary incidence is discussed in the present review.

  7. 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.

  8. 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- ...

  9. 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- ...

  10. 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 ( ...

  11. 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 ...

  12. 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 ...

  13. Causes of High Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Causes of High Cholesterol Updated:Jul 5,2017 If you have high ... and procedures related to heart disease and stroke. Cholesterol • Home • About Cholesterol • HDL, LDL, and Triglycerides • Causes ...

  14. 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 ...

  15. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jul 5,2017 How ... do you know about cholesterol? Here are some common misconceptions — and the truth. High cholesterol isn’t ...

  16. 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.

  17. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

    Directory of Open Access Journals (Sweden)

    Patrick Linsel-Nitschke

    Full Text Available BACKGROUND: Rare mutations of the low-density lipoprotein receptor gene (LDLR cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD. Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. METHODS: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. FINDINGS: Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11% was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI [0.13-0.24] mmol/L, p = 1.5x10(-10. This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7. Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. CONCLUSION: A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.

  18. Lifelong Reduction of LDL-Cholesterol Related to a Common Variant in the LDL-Receptor Gene Decreases the Risk of Coronary Artery Disease—A Mendelian Randomisation Study

    Science.gov (United States)

    Linsel-Nitschke, Patrick; Götz, Anika; Erdmann, Jeanette; Braenne, Ingrid; Braund, Peter; Hengstenberg, Christian; Stark, Klaus; Fischer, Marcus; Schreiber, Stefan; El Mokhtari, Nour Eddine; Schaefer, Arne; Schrezenmeier, Jürgen; Rubin, Diana; Hinney, Anke; Reinehr, Thomas; Roth, Christian; Ortlepp, Jan; Hanrath, Peter; Hall, Alistair S.; Mangino, Massimo; Lieb, Wolfgang; Lamina, Claudia; Heid, Iris M.; Doering, Angela; Gieger, Christian; Peters, Annette; Meitinger, Thomas; Wichmann, H.-Erich; König, Inke R.; Ziegler, Andreas; Kronenberg, Florian; Samani, Nilesh J.; Schunkert, Heribert

    2008-01-01

    Background Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. Methods Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. Findings Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13–0.24] mmol/L, p = 1.5×10−10). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76–0.89], p = 2.1×10−7). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. Conclusion A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD. PMID:18714375

  19. HDL Cholesterol: How to Boost Your 'Good' Cholesterol

    Science.gov (United States)

    HDL cholesterol: How to boost your 'good' cholesterol Your cholesterol levels are an important measure of heart health. For HDL cholesterol, or "good" cholesterol, higher levels are better. By Mayo Clinic ...

  20. 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.

  1. 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 ...

  2. 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.

  3. Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

    Science.gov (United States)

    Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

    2014-04-27

    absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved. Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117].

  4. Wheat alkylresorcinols reduce micellar solubility of cholesterol in vitro and increase cholesterol excretion in mice.

    Science.gov (United States)

    Horikawa, Kazumasa; Hashimoto, Chiaki; Kikuchi, Yosuke; Makita, Miki; Fukudome, Shin-Ichi; Okita, Kimiko; Wada, Naoyuki; Oishi, Katsutaka

    2017-03-01

    Epidemiological studies have shown that the consumption of whole grains can reduce risk for metabolic disorders. We recently showed that chronic supplementation with wheat alkylresorcinols (ARs) prevents glucose intolerance and insulin resistance with hepatic lipid accumulation induced in mice by a high-fat high-sucrose diet (HFHSD). This study examines the effects of ARs on the micellar solubility of cholesterol in vitro, as well as the effects of transient AR supplementation on faecal lipid excretion and plasma lipid levels in mice. We found that ARs formed bile micelles with taurocholate independently of phospholipids, and dose-dependently decreased the micellar solubility of cholesterol in a biliary micelle model. Transient AR supplementation with HFHSD increased faecal cholesterol and triglyceride contents and decreased plasma cholesterol concentrations. These suggest that one underlying mechanism through which ARs suppress diet-induced obesity is by interfering with the micellar cholesterol solubilisation in the digestive tract, which subsequently decreases cholesterol absorption.

  5. 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 ...

  6. 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 ...

  7. 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, ...

  8. 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.

  9. High blood cholesterol levels

    Science.gov (United States)

    ... 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. ...

  10. 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.

  11. 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

  12. 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.

  13. No Decrease of HDL Cholesterol after 6 Days of Low Fat and High Carbohydrate Diets in a Young Chinese Han Pop-ulation%中国汉族青年低脂高糖膳食6天后的血清高密度脂蛋白、胆固醇水平

    Institute of Scientific and Technical Information of China (English)

    李正科; 汤慧; 龚仁蓉; 林佳; 甘禅芬; 黄鑫; 李蓉辉; 方定志

    2008-01-01

    More studies are needed on the hyperyriacylglycerolemic effects of low fat and high carbohydrate (LF-HC) diet in young population, especially Chinese who generally have a diet containing lower fat and higher carbohydrate. To test them in a young Chinese Han population, 56 healthy subjects (22.89±1.80) years were given regular diet of 31% fat and 54% carbohy-drate for 7 days, followed by LF-HC diet of 15% fat and 70% carbohydrate for 6 days, without total energy restriction. After the LF-HC diet, the male experienced an increase of high density lipoprutein (HDL) cholesterol and decreases of weight, body mass index (BMI), total cholesterol (TC), and LDL (low density lipoprotein) cholesterol (P < 0.05). The female experienced in-creased serum triacylglycerol and insulin, and decreased TC and LDL cholesterol (P < 0.05). When BMI was taken into account,all the subjects with low, medium, or high BMI experienced decreases of TC and LDL cholesterol although some changes were not significant. No significant decrease of HDL cholesterol was found, while significantly increased HDL cholesterol and apolipoprotein A-Ⅰ (apo A- Ⅰ) were found in the male subjects with low or high BMI (P < 0.05). Significant increase of triacylglycerol was observed only in the female subjects with low or medium BMI. In conclusion, subjects with different BMI and gender have different triacylglycerol and HDL cholesterol responses to LF-HC diets, and significant increase of HDL cholesterol and apolipoprotein A- Ⅰ were observed in some young male subjects.%目的 探讨低脂高糖膳食对中国汉族青年血脂及载脂蛋白的影响.方法 我室招募健康在校大学生自愿者56名((22.89±1.80)岁],于7 d平衡膳食后给予低脂高糖膳食6 d,分别在第1 d、8 d、14 d清晨收集受试者人类学指标并抽取空腹静脉血,测定血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血糖(GLU)、 胰岛

  14. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    Institute of Scientific and Technical Information of China (English)

    Ryan; E; Temel; J; Mark; Brown

    2010-01-01

    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-media...

  15. What Your Cholesterol Levels Mean

    Science.gov (United States)

    ... 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 ...

  16. 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) ...

  17. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    Science.gov (United States)

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  18. Low cholesterol and violence.

    Science.gov (United States)

    Mufti, R M; Balon, R; Arfken, C L

    1998-02-01

    The association between violent behavior and low serum total cholesterol levels was examined in a psychiatric inpatient population with diverse diagnoses. The study used a case-control design to compare the cholesterol levels of patients in a long-term psychiatric hospital who had a history of seclusion or restraints (N = 20) and those who did not (N = 20). A low cholesterol level was defined as less than 180 mg/dL. A strong association was found between low cholesterol levels and violent behavior (odds ratio = 15.49), an association that was not due to age, race, sex, or diagnosis. The finding was consistent whether mean levels or dichotomized levels of cholesterol were examined. Physical health, cholesterol-lowering medication, current alcohol use, or unusual diets could not explain the results. However, the raw frequency of episodes of seclusion or restraint as an indicator of the frequency of violent behavior was not associated with cholesterol level. Dichotomizing cholesterol levels at 180 mg/dL yielded high sensitivity (90 percent) for predicting violent behavior but at the cost of low specificity (65 percent). The results support the hypothesis that an association exists between low cholesterol and violent behavior among psychiatric patients but argue against using cholesterol level as a screening tool for predicting violent behavior.

  19. 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.

  20. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  1. 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.

  2. 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 ...

  3. 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.

  4. Heating Two Types of Enriched Margarine: Complementary Analysis of Phytosteryl/Phytostanyl Fatty Acid Esters and Phytosterol/Phytostanol Oxidation Products.

    Science.gov (United States)

    Scholz, Birgit; Menzel, Nicole; Lander, Vera; Engel, Karl-Heinz

    2016-04-06

    Two phytosteryl and/or phytostanyl fatty acid ester-enriched margarines were subjected to common heating procedures. UHPLC-APCI-MS analysis resulted for the first time in comprehensive quantitative data on the decreases of individual phytosteryl/-stanyl fatty acid esters upon heating of enriched foods. These data were complemented by determining the concurrently formed phytosterol/-stanol oxidation products (POPs) via online LC-GC. Microwave-heating led to the least decreases of esters of approximately 5% in both margarines. Oven-heating of the margarine in a casserole caused the greatest decreases, with 68 and 86% esters remaining, respectively; the impact on individual esters was more pronounced with increasing degree of unsaturation of the esterified fatty acids. In the phytosteryl/-stanyl ester-enriched margarine, approximately 20% of the ester losses could be explained by the formation of POPs; in the phytostanyl ester-enriched margarine, the POPs accounted for <1% of the observed ester decreases.

  5. 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 ...

  6. 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 ...

  7. 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

  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. 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.

  10. 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...

  11. 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

  12. 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 ...

  13. Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice.

    Science.gov (United States)

    Dimova, Lidiya G; de Boer, Jan Freark; Plantinga, Josee; Plösch, Torsten; Hoekstra, Menno; Verkade, Henkjan J; Tietge, Uwe J F

    2017-08-01

    In nematodes, the intestine senses and integrates early life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from maternal milk and investigate the consequences of decreased milk cholesterol availability, early in life, on the metabolism of cholesterol in adult mice. We blocked intestinal absorption of cholesterol in milk fed to newborn mice by supplementing the food of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted into milk. Ezetimibe interacts with the intestinal cholesterol absorption transporter NPC1l1 to block cholesterol uptake into enterocytes. Characterization of these offspring at 24 weeks of age showed a 27% decrease in cholesterol absorption (P cholesterol transporters, in the proximal small intestine. We observed increased histone H3K9me3 methylation at positions -423 to -607 of the proximal Npc1l1 promoter in small intestine tissues from 24-week-old offspring fed ezetimibe during lactation, compared with controls. These findings show that the early postnatal mammalian intestine functions as an environmental sensor of nutritional conditions, responding to conditions such as low cholesterol levels by epigenetic modifications of genes. Further studies are needed to determine how decreased sterol absorption for a defined period might activate epigenetic regulators; the findings of our study might have implications for human infant nutrition and understanding and preventing cardiometabolic disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. 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).

  15. 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.

  16. Cholesterol through the Looking Glass

    Science.gov (United States)

    Kristiana, Ika; Luu, Winnie; Stevenson, Julian; Cartland, Sian; Jessup, Wendy; Belani, Jitendra D.; Rychnovsky, Scott D.; Brown, Andrew J.

    2012-01-01

    How cholesterol is sensed to maintain homeostasis has been explained by direct binding to a specific protein, Scap, or through altering the physical properties of the membrane. The enantiomer of cholesterol (ent-cholesterol) is a valuable tool in distinguishing between these two models because it shares nonspecific membrane effects with native cholesterol (nat-cholesterol), but not specific binding interactions. This is the first study to compare ent- and nat-cholesterol directly on major molecular parameters of cholesterol homeostasis. We found that ent-cholesterol suppressed activation of the master transcriptional regulator of cholesterol metabolism, SREBP-2, almost as effectively as nat-cholesterol. Importantly, ent-cholesterol induced a conformational change in the cholesterol-sensing protein Scap in isolated membranes in vitro, even when steps were taken to eliminate potential confounding effects from endogenous cholesterol. Ent-cholesterol also accelerated proteasomal degradation of the key cholesterol biosynthetic enzyme, squalene monooxygenase. Together, these findings provide compelling evidence that cholesterol maintains its own homeostasis not only via direct protein interactions, but also by altering membrane properties. PMID:22869373

  17. Enzymatic quantification of cholesterol and cholesterol esters from silicone hydrogel contact lenses.

    Science.gov (United States)

    Pucker, Andrew D; Thangavelu, Mirunalni; Nichols, Jason J

    2010-06-01

    The purpose of this work was to develop an enzymatic method of quantification of cholesterol and cholesterol esters derived from contact lenses, both in vitro and ex vivo. Lotrafilcon B (O2 Optix; CIBA Vision, Inc., Duluth, GA) and galyfilcon A (Acuvue Advance; Vistakon, Inc., Jacksonville, FL) silicone hydrogel contact lenses were independently incubated in cholesterol oleate solutions varying in concentrations. After incubation, the lenses were removed and underwent two separate 2:1 chloroform-methanol extractions. After in vitro studies, 10 human subjects wore both lotrafilcon B and galyfilcon A contact lenses for 7 days. The lenses also underwent two separate 2:1 chloroform-methanol extractions. All in vitro and ex vivo samples were quantified with a cholesterol esterase enzymatic reaction. Calibration curves from quantifications of in vitro contact lens samples soaked in successively decreasing concentrations of cholesterol oleate yielded coefficients of determination (R(2)) of 0.99 (lotrafilcon B) and 0.97 (galyfilcon A). For in vitro contact lens samples, galyfilcon A was associated with an average cholesterol oleate extraction of 39.85 +/- 48.65 microg/lens, whereas lotrafilcon B was associated with 5.86 +/- 3.36 microg/lens (P = 0.05) across both extractions and all incubation concentrations. For ex vivo contact lens samples, there was significantly more cholesterol and cholesterol esters deposited on galyfilcon A (5.77 +/- 1.87 microg/lens) than on lotrafilcon B (2.03 +/- 1.62 microg/lens; P = 0.0005). This is an efficient and simple method of quantifying total cholesterol extracted from silicone hydrogel contact lenses and, potentially, the meibum and/or tear film. Certain silicone hydrogel materials demonstrate more affinity for cholesterol and its esters than do others.

  18. Flow-mediated vasodilation is not impaired when HDL-cholesterol is lowered by substituting carbohydrates for monounsaturated fat

    NARCIS (Netherlands)

    de Roos, NM; Bots, ML; Siebelink, E; Katan, MB

    2001-01-01

    Low-fat diets, in which carbohydrates replace some of the fat, decrease serum cholesterol. This decrease is due to decreases in LDL-cholesterol but in part to possibly harmful decreases in HDL-cholesterol. High-oil diets, in which oils rich in monounsaturated fat replace some of the saturated fat, d

  19. Flow-mediated vasodilation is not impaired when HDL-cholesterol is lowered by substituting carbohydrates for monounsaturated fat

    NARCIS (Netherlands)

    de Roos, NM; Bots, ML; Siebelink, E; Katan, MB

    2001-01-01

    Low-fat diets, in which carbohydrates replace some of the fat, decrease serum cholesterol. This decrease is due to decreases in LDL-cholesterol but in part to possibly harmful decreases in HDL-cholesterol. High-oil diets, in which oils rich in monounsaturated fat replace some of the saturated fat, d

  20. 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.

  1. 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.

  2. 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.

  3. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

    Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2010-09-01

    Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

  4. Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol

    Science.gov (United States)

    Soni, Vinay; Hedroug, Omar; Annaba, Fadi; Dudeja, Amish; Shen, Le; Turner, Jerrold R.; Khramtsova, Ekaterina A.; Saksena, Seema; Dudeja, Pradeep K.; Gill, Ravinder K.; Alrefai, Waddah A.

    2014-01-01

    Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse liver was shown to have no effect on plasma cholesterol. However, the influence of activating intestinal SREBP2 on plasma cholesterol is not known. We have generated a novel transgenic mouse model with intestine specific overexpression of active SREBP2 (ISR2) driven by villin promoter. ISR2 mice showed overexpression of active SREBP2 specifically in the intestine. Microarray analysis of jejunal RNA from ISR2 mice showed a significant increase in genes involved in fatty acid and cholesterol synthesis. Cholesterol and triglyceride (TG) in jejunum and liver (mg/g protein) were significantly increased in ISR2 vs wild type mice. Serum Cholesterol was significantly increased in VLDL and LDL fractions whereas the level of serum triglycerides was decreased in ISR2 vs wild type mice. In conclusion, activation of intestinal SREBP2 alone seems to be sufficient to increase plasma cholesterol, highlighting the essential role of intestine in maintaining cholesterol homeostasis in the body. PMID:24465397

  5. 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

  6. Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux : an observational study

    NARCIS (Netherlands)

    van Dam, MJ; de Groot, E; Clee, SM; Hovingh, GK; Roelants, R; Brooks-Wilson, A; Zwinderman, AH; Smit, AJ; Smelt, A.H.; Groen, AK; Hayden, MR; Kastelein, JJP

    2002-01-01

    Background Decreased concentrations of HDL cholesterol are associated with increased cardiovascular risk. These concentrations are directly related to cholesterol efflux from cells-the first step and a key process in reverse cholesterol transport. Cholesterol efflux is mediated by the ATP-binding ca

  7. 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

  8. 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)

  9. 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

  10. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

  12. 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

  13. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling.

    Science.gov (United States)

    York, Autumn G; Williams, Kevin J; Argus, Joseph P; Zhou, Quan D; Brar, Gurpreet; Vergnes, Laurent; Gray, Elizabeth E; Zhen, Anjie; Wu, Nicholas C; Yamada, Douglas H; Cunningham, Cameron R; Tarling, Elizabeth J; Wilks, Moses Q; Casero, David; Gray, David H; Yu, Amy K; Wang, Eric S; Brooks, David G; Sun, Ren; Kitchen, Scott G; Wu, Ting-Ting; Reue, Karen; Stetson, Daniel B; Bensinger, Steven J

    2015-12-17

    Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity.

  14. 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.

  15. Statins and the cholesterol mortality paradox.

    Science.gov (United States)

    Nunes, José Pedro L

    2017-02-01

    Large-scale randomised controlled trials, carried out in the context of secondary cardiovascular prevention, have shown that statins are superior to placebo: these drugs were shown to decrease cardiovascular events and total mortality. A further set of clinical trials compared high intensity to low/standard intensity LDL cholesterol lowering in the same setting (using either statins or a statin/ezetimibe association). In this case, a decrease in LDL cholesterol and a concomitant significant reduction in cardiovascular events were seen with intensive therapy, however with no change in total mortality. This phenomenon we may term the LDL cholesterol mortality paradox. It could be due either to the prevention (by high-intensity therapy) of episodes not severe enough to lead to the death of patients, or to high-intensity therapy leading to the death of some patients at the same time as preventing the death of others, with a null aggregate effect. Several types of adverse effects have been seen with statin therapy, such as a possible increased incidence of Diabetes mellitus and of myopathy. The decision to start high-intensity LDL cholesterol lowering (rather than low- or moderate-intensity statin treatment) should be evaluated on a case-by-case basis, taking into consideration the overall aspects of each patient, including the patient's preferences. High-intensity LDL cholesterol lowering, up to the present moment, has failed to produce a change in overall prognosis (total mortality), and should not therefore be mandatory in secondary cardiovascular prevention. It remains to be seen if a similar LDL cholesterol mortality paradox occurs with new drugs targeting plasma lipids.

  16. 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.

  17. Effect of doxazosin on cholesterol synthesis in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    D' Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice

    Science.gov (United States)

    Zhang, Yuan; Breevoort, Sarah R.; Angdisen, Jerry; Fu, Mingui; Schmidt, Daniel R.; Holmstrom, Sam R.; Kliewer, Steven A.; Mangelsdorf, David J.; Schulman, Ira G.

    2012-01-01

    Liver X receptors (LXRα and LXRβ) are important regulators of cholesterol and lipid metabolism, and their activation has been shown to inhibit cardiovascular disease and reduce atherosclerosis in animal models. Small molecule agonists of LXR activity are therefore of great therapeutic interest. However, the finding that such agonists also promote hepatic lipogenesis has led to the idea that hepatic LXR activity is undesirable from a therapeutic perspective. To investigate whether this might be true, we performed gene targeting to selectively delete LXRα in hepatocytes. Liver-specific deletion of LXRα in mice substantially decreased reverse cholesterol transport, cholesterol catabolism, and cholesterol excretion, revealing the essential importance of hepatic LXRα for whole body cholesterol homeostasis. Additionally, in a pro-atherogenic background, liver-specific deletion of LXRα increased atherosclerosis, uncovering an important function for hepatic LXR activity in limiting cardiovascular disease. Nevertheless, synthetic LXR agonists still elicited anti-atherogenic activity in the absence of hepatic LXRα, indicating that the ability of agonists to reduce cardiovascular disease did not require an increase in cholesterol excretion. Furthermore, when non-atherogenic mice were treated with synthetic LXR agonists, liver-specific deletion of LXRα eliminated the detrimental effect of increased plasma triglycerides, while the beneficial effect of increased plasma HDL was unaltered. In sum, these observations suggest that therapeutic strategies that bypass the liver or limit the activation of hepatic LXRs should still be beneficial for the treatment of cardiovascular disease. PMID:22484817

  20. 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 ...

  1. 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

  2. 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.

  3. 17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.;

    2001-01-01

    .20% naringenin, for 16 weeks. The uterine weight was increased (P cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...... cholesterol was increased (P cholesterol accumulation was decreased (P ... but the ratio of intima to media and area of intima in ascending, thoracic, and abdominal aorta were not significantly different. In the naringenin group the only differences, compared with the control group, were increased LDL cholesterol (P

  4. Transfer of cholesterol from macrophages to lymphocytes in culture.

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

    -cultivation with macrophages decreased the basal incorporation of [2-14C]thymidine into lymphocyte DNA and the addition of cholesterol to lymphocyte culture media also impaired the lymphocyte proliferative response to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS). The above results suggest that macrophages may transfer cholesterol to lymphocytes (from both lymph nodes and blood), thus regulating lymphocyte function by raising the intracellular cholesterol content and suppressing lymphocyte proliferative activity. If this is so, a modulatory role for the transfer of cholesterol in both physiological (e.g. immune response) and pathological conditions (e.g. atherosclerosis) may be postulated. This hypothesis is currently under investigation in our laboratory.

  5. 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.

  6. Cholesterol detection using optical fiber sensor based on intensity modulation

    Science.gov (United States)

    Budiyanto, Moh; Suhariningsih; Yasin, Moh

    2017-05-01

    The aim of the research is to detect the concentration of cholesterol by using the principle that a laser beam propagation is guided by optical fiber bundle in term of intensity profile through solution with vary concentrations of cholesterol from 0 to 300 ppm. The mechanism of cholesterol concentration detection is the propagation of He-Ne laser beam with wavelength of 632.5 nm through a fiber optic bundle and a solution of cholesterol, then is reflected by a flat mirror and enters receiving fiber. This signal is captured by a silicon detector (SL-818, Newport) in the form of output voltage. The result showed that the output voltage decrease linearly with the increase of concentration of cholesterol with a sensitivity of 0.0004 mV/ppm and the linearity more than 97%.

  7. The hedgehog receptor patched is involved in cholesterol transport.

    Directory of Open Access Journals (Sweden)

    Michel Bidet

    Full Text Available BACKGROUND: Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened. METHODOLOGY/PRINCIPAL FINDINGS: Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol. CONCLUSION/SIGNIFICANCE: Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway

  8. 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

  9. Insoluble fraction of buckwheat (Fagopyrum esculentum Moench) protein possessing cholesterol-binding properties that reduce micelle cholesterol solubility and uptake by Caco-2 cells.

    Science.gov (United States)

    Metzger, Brandon T; Barnes, David M; Reed, Jess D

    2007-07-25

    Buckwheat (Fagopyrum esculentum Moench) protein (BWP) exhibits hypocholesterolemic activity in several animal models by increasing fecal excretion of neutral and acidic sterols. In the current study, the ability of BWP to disrupt micelle cholesterol solubility by sequestration of cholesterol was investigated. When BWP (0.2%) was incubated with cholesterol and micelle lipid components prior to micelle formation, cholesterol solubility was reduced 40%. In contrast, cholesterol solubility was not decreased when BWP (0.2%) was incubated after micelle formation and incorporation of soluble cholesterol. Buckwheat flour, from which BWP was derived, had no significant effect on cholesterol solubility. Cholesterol uptake in Caco-2 cells from micelles made in the presence of BWP (0.2%) was reduced by 47, 36, 35, and 33% when compared with buckwheat flour, bovine serum albumin, casein, and gelatin, respectively. Reduction in cholesterol uptake in Caco-2 cells was dose-dependent, with maximum reductions at 0.1-0.4% BWP. In cholesterol-binding experiments, 83% of the cholesterol was associated with an insoluble BWP fraction, indicating strong cholesterol-binding capacity that disrupts solubility and uptake by Caco-2 cells.

  10. Regulation of neutral cholesterol esterase and acyl-CoA : cholesterol acyltransferase in the rat adrenal gland.

    Science.gov (United States)

    Beins, D M; Vining, R; Balasubramaniam, S

    1982-03-15

    The activities of neutral cholesterol esterase and acyl-CoA : cholesterol acyltransferase in rat adrenal gland were measured at various time intervals over 24 h. The activity of cholesterol esterase displayed diurnal rhythm, with a major peak at the onset of darkness coinciding with the peak in the diurnal rhythm of plasma corticosterone concentration. The activity of acyl-CoA : cholesterol acyltransferase also exhibited a characteristic diurnal rhythm, with the minimum activity occurring 3 h after the onset of darkness. The profile of the rhythm exhibited by the activity of the esterifying enzyme was similar to the mirror image of the pattern of diurnal rhythm in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Microsomal non-esterified cholesterol showed a gradual decline with a significant decrease in concentration at the onset of darkness, thus suggesting that diurnal removal of cholesterol in the environment of the esterifying enzyme and hydroxymethylglutaryl-CoA reductase leads to such diurnal decrease or increase in the activities of these two enzymes. Acute administration of corticotropin led to a 3-fold increase in the activity of cholesterol esterase, a 50% decrease in the activity of acyl-CoA : cholesterol acyltransferase and a 2-fold increase in the activity of hydroxymethylglutaryl-CoA reductase. Corticotropin administration also resulted in a significant decrease in microsomal non-esterified cholesterol and increase in plasma corticosterone concentration. These observations suggest that corticotropin plays an important part in generating the diurnal rhythm in the activities of the three enzymes.

  11. Modulating cancer cell survival by targeting intracellular cholesterol transport.

    Science.gov (United States)

    Kuzu, Omer F; Gowda, Raghavendra; Noory, Mohammad A; Robertson, Gavin P

    2017-08-08

    Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.

  12. 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.

  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. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Cholesterol removal from various samples by cholesterol-imprinted monosize microsphere-embedded cryogels.

    Science.gov (United States)

    Çaktü, Kıvılcım; Baydemir, Gözde; Ergün, Bahar; Yavuz, Handan

    2014-12-01

    Cholesterol-imprinted monosize poly(glycidyl methacrylate-N-methacryloyl-(L)-tyrosine methylester) microspheres were embedded into the poly(hydroxyethyl methacrylate) (PHEMA) cryogels and the resulting composite cryogel was used for the selective removal of cholesterol. Composite cryogels were characterized by swelling tests, multipoint BET apparatus, SEM, FTIR and elemental analysis studies. Specific surface area of the PHEMA cryogel was increased from 13 to 72.7 m(2)/g by embedding of microspheres. Composite cryogels removed 80% of cholesterol from homogenized milk. The maximum adsorption capacity was found as 42.7 mg/g for intestinal mimicking solution. After 20 adsorption-desorption cycles, there was no remarkable decrease in the adsorption capacity.

  19. [The real measurement of non-HDL-cholesterol: Atherogenic cholesterol].

    Science.gov (United States)

    Millán, Jesús; Hernández-Mijares, Antonio; Ascaso, Juan F; Blasco, Mariano; Brea, Angel; Díaz, Ángel; González-Santos, Pedro; Mantilla, Teresa; Pedro-Botet, Juan; Pintó, Xavier

    Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  20. [Erythrocyte cholesterol content in polycythemia vera: relation to ischemic heart disease].

    Science.gov (United States)

    Torkhovskaia, T I; Khalilov, E M; Gorokhovskaia, G N; Fortinskaia, E S; Soboleva, V V; Kochetova, M M; Nikitina, N A; Martynov, A I

    2003-01-01

    Relative cholesterol content and its distribution between erythrocytes and plasma were studied in 34 patients with polycythemia vera (PV) both with and without concomitant coronary heart disease (CHD). Deformability of erythrocytes, disturbances of microcirculation (blood flow fragmentation, decrease of capillary density) were also assessed. Erythrocytes cholesterol/phospholipids molar ratios (0.68+/-0.03) in patients was lower than normal value (0.8) in spite of decreased cell deformability. This was associated with some increase of peroxidation products. Blood cholesterol distribution between cell and plasma species had some peculiarities caused by high hematocrit: compared with normal value erythrocytes of patients carried relatively larger portion of total blood cholesterol (23.7+/-0.8% and 27-31%, respectively). However in CHD patients these values were significantly lower with correspondent increase of plasma cholesterol quota. This allowed to suggest possible protective role of blood cholesterol redistribution in polycythemia patients, through erythrocytes trafficking of some part of plasma cholesterol.

  1. 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.

  2. EVALUATION OF SERUM CHOLESTEROL, AMINO TRANSFERASES

    Directory of Open Access Journals (Sweden)

    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.

  3. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    Science.gov (United States)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  4. Ezetimibe: a selective cholesterol absorption inhibitor.

    Science.gov (United States)

    Nutescu, Edith A; Shapiro, Nancy L

    2003-11-01

    Ezetimibe is the first agent of a novel class of selective cholesterol absorption inhibitors recently approved by the Food and Drug Administration for treatment in the United States. Ezetimibe inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids. Ezetimibe localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes. Preclinical studies demonstrated lipid-lowering properties of ezetimibe as monotherapy and showed a synergistic effect in combination with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The efficacy and safety of ezetimibe 10 mg/day have been established in phase III clinical trials. In these trials, ezetimibe was investigated as monotherapy, as an add-on to ongoing statin therapy, and as combination therapy with statins in patients with primary hypercholesterolemia. In addition, ezetimibe has been evaluated in patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia. When given as monotherapy or in combination with statins or fenofibrate, ezetimibe reduces low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5%. Unlike other intestinally acting lipid-lowering agents, ezetimibe does not adversely affect triglyceride levels and, due to its minimal systemic absorption, drug interactions are few. Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins. In clinical practice, ezetimibe has a role as monotherapy for patients who require modest LDL reductions or cannot tolerate other lipid-lowering agents. In combination therapy with a statin, ezetimibe is used in patients who cannot tolerate high statin doses or in those who need additional LDL reductions despite maximum statin doses.

  5. 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.

  6. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-08-30

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis.

  7. Bacterial colonization of host cells in the absence of cholesterol.

    Directory of Open Access Journals (Sweden)

    Stacey D Gilk

    2013-01-01

    Full Text Available Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24(-/- mouse embryonic fibroblasts (MEFs. DHCR24(-/- MEFs lack the Δ24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24(-/- MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens: Coxiella burnetii, Salmonella enterica serovar Typhimurium, and Chlamydia trachomatis. Invasion by S. Typhimurium and C. trachomatis was unaltered in DHCR24(-/- MEFs. In contrast, C. burnetii entry was significantly decreased in -cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated α(Vβ(3 integrin was blocked, suggesting a role for lipid rafts in C. burnetii uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the C. burnetii-occupied vacuole within DHCR24(-/- MEFs lacked the CD63-positive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by S. Typhimurium and C. trachomatis, but plays a role in C. burnetii-host cell interactions.

  8. Bacterial Colonization of Host Cells in the Absence of Cholesterol

    Science.gov (United States)

    Gilk, Stacey D.; Cockrell, Diane C.; Luterbach, Courtney; Hansen, Bryan; Knodler, Leigh A.; Ibarra, J. Antonio; Steele-Mortimer, Olivia; Heinzen, Robert A.

    2013-01-01

    Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24−/− mouse embryonic fibroblasts (MEFs). DHCR24−/− MEFs lack the Δ24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24−/− MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens: Coxiella burnetii, Salmonella enterica serovar Typhimurium, and Chlamydia trachomatis. Invasion by S. Typhimurium and C. trachomatis was unaltered in DHCR24−/− MEFs. In contrast, C. burnetii entry was significantly decreased in −cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated αVβ3 integrin was blocked, suggesting a role for lipid rafts in C. burnetii uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the C. burnetii-occupied vacuole within DHCR24−/− MEFs lacked the CD63-postive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by S. Typhimurium and C. trachomatis, but plays a role in C. burnetii-host cell interactions. PMID:23358892

  9. HDL (Good), LDL (Bad) Cholesterol and Triglycerides

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More HDL (Good), LDL (Bad) Cholesterol and Triglycerides Updated:Jul 5,2017 Cholesterol isn’t just ... Your Cholesterol Score Explained What Are High Blood Cholesterol and Triglycerides? How Can I Improve My Cholesterol? | Spanish What ...

  10. What Do My Cholesterol Levels Mean?

    Science.gov (United States)

    ... results: total cholesterol, LDL (“bad”) and HDL (“good”) cholesterol, and triglycerides (blood fats). What should my total cholesterol level ... I Improve My Cholesterol? What Are High Blood Cholesterol and Triglycerides? What Is High Blood Pressure? How Can I ...

  11. Prevention and Treatment of High Cholesterol (Hyperlipidemia)

    Science.gov (United States)

    ... too many lipids (fats) in it, i.e., cholesterol and triglycerides. In hypercholesterolemia, there’s too much LDL (bad) cholesterol ... Your Cholesterol Score Explained What Are High Blood Cholesterol and Triglycerides? How Can I Improve My Cholesterol? | Spanish What ...

  12. HDL cholesterol: atherosclerosis and beyond

    NARCIS (Netherlands)

    Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

  13. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-01-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation. PMID:28255164

  14. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  15. 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 ...

  16. 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 – ...

  17. Estimations of cholesterol, triglycerides and fractionation of ...

    African Journals Online (AJOL)

    Estimations of cholesterol, triglycerides and fractionation of lipoproteins in serum samples of some Nigerian female subjects. ... low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) ... Article Metrics.

  18. 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

  19. Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

    2017-06-25

    Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. 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.

  2. 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.

  3. Americans' Cholesterol Levels Keep Falling

    Science.gov (United States)

    ... 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K W; Macfarlane, D.G.

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

  8. 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.

  9. Steroidal Triterpenes of Cholesterol Synthesis

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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 ...

  12. 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.

  13. Antihyperlipidemic effect of sesame (Sesamum indicum L.) protein isolate in rats fed a normal and high cholesterol diet.

    Science.gov (United States)

    Biswas, Arundhati; Dhar, Pubali; Ghosh, Santinath

    2010-01-01

    The dietary influence of sesame protein isolate (protein content 91.5%), produced from dehulled, defatted sesame meal, on blood and tissue lipid profile and lipid peroxidation has been assessed in normal and hypercholesterolemic rats. To evaluate their hypocholesterolemic and antioxidative activity in vivo, we fed 18% sesame protein isolate with or without 2% cholesterol in comparison with casein to rats for 28 d. We determined plasma total protein, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triacylglycerol as well as susceptibility of plasma and erythrocyte membrane lipid to oxidation ex vivo. Liver tissue lipid, cholesterol, phospholipids, and lipid peroxidations were also determined. The total cholesterol, LDL-cholesterol and triacylglycerol levels were significantly reduced in the sesame protein isolate and isolate containing cholesterol group than the corresponding control casein groups. HDL-cholesterol level was also increased in sesame protein isolate (41%) and protein isolate containing cholesterol group (38%) than the corresponding control casein and casein containing cholesterol groups. There was 49% and 64% lowering of plasma lipid peroxidation as well as 36% and 56% lowering of lipoprotein oxidation susceptibility (LOS) in the 2 experimental groups (sesame protein isolate and isolate containing cholesterol group) than the corresponding control (casein and casein containing cholesterol) groups. There was significant lowering of erythrocyte membrane lipid peroxidation (68% and 63% lowering in sesame protein isolate and isolate containing cholesterol groups) and liver lipid peroxidation (61% and 76% lowering in the 2 experimental groups than the corresponding control casein groups). Therefore, our results indicate that sesame protein isolate decreases cholesterol concentration in plasma, increases HDL-cholesterol, and also decreases plasma and erythrocyte membrane lipid peroxidation with or

  14. The usefulness of total cholesterol and high density lipoprotein ...

    African Journals Online (AJOL)

    The usefulness of total cholesterol and high density lipoprotein - cholesterol ratio in ... cholesterol and/or highdensity lipoprotein cholesterol/total cholesterol ratios in the interpretation of lipid profile result in clinical practice. ... Article Metrics.

  15. Cholesterol Removal from Whole Egg by Crosslinked β-Cyclodextrin

    Directory of Open Access Journals (Sweden)

    H. J. Jeong

    2014-04-01

    Full Text Available This study was carried out to optimize cholesterol removal in whole egg using crosslinked β-cyclodextrin (β-CD and to recycle the β-CD. Various factors for optimizing conditions were concentration of the β-CD, mixing temperature, mixing time, mixing speed and centrifugal speed. In the result of this study, the optimum conditions of cholesterol removal were 25% crosslinked β-CD, 40°C mixing temperature, 30 min mixing time, 1,200 rpm mixing speed and 2,810×g centrifugal speed. The recycling was repeated five times. The cholesterol removal was 92.76% when treated with the optimum conditions. After determining the optimum conditions, the recyclable yields of the crosslinked β-CD ranged from 86.66% to 87.60% in the recycling and the percentage of cholesterol removal was over 80% until third recycling. However, the cholesterol removal efficiency was decreased when the number of repeated recycling was increased. Based on the result of this study, it was concluded that the crosslinked β-CD was efficient for cholesterol removal in whole egg, and recycling is possible for only limited repeating times due to the interaction of the β-CD and egg protein.

  16. An activation-collision mechanism for cholesterol transfer between membranes.

    Science.gov (United States)

    Steck, T L; Kezdy, F J; Lange, Y

    1988-09-15

    We report the results of experiments which show that cholesterol transfer between membranes cannot proceed by aqueous diffusion, as widely held, but must involve a more complex mechanism. (a) The rate of transfer of [3H]cholesterol from red blood cells was found to vary inversely with the size of the acceptor particle (ghosts, vesicles of ghosts, liposomes, and plasma lipoproteins). (b) The transfer of [3H]cholesterol from red blood cells to ghosts was accelerated by the presence of plasma, even though the plasma competed with the ghosts as an acceptor. (c) The rate of transfer of [3H]cholesterol from red blood cells to ghosts decreased to zero with increasing dilution but was not simply second-order. (d) The cholesterol in retinal rod disc membranes is not at equilibrium with plasma lipoproteins in that disc cholesterol increased when the homogenates were incubated in vitro with plasma. (e) The kinetics of cholesterol transfer cannot be limited by unstirred layer effects since the transfer of lysolecithin in the same system was faster than that of cholesterol by 3 orders of magnitude. The simplest model compatible with all the data suggests a two-step pathway involving a first-order followed by a second-order process. The first step could be a unimolecular activation event, perhaps the movement of the sterol in the donor particle to a more exposed (hydrated) position. In the second step, the activated sterol would be transferred during transient collisions between donor and acceptor particles. When collision is not rate-limiting, the overall process would appear to be simply first-order, hence kinetically indistinguishable from the aqueous diffusion mechanism. The activation-collision model thus not only rationalizes our data but is also consistent with the simpler kinetics previously reported for the transfer of both membrane phospholipids and sterols.

  17. Cholesterol depletion disorganizes oocyte membrane rafts altering mouse fertilization.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Drastic membrane reorganization occurs when mammalian sperm binds to and fuses with the oocyte membrane. Two oocyte protein families are essential for fertilization, tetraspanins and glycosylphosphatidylinositol-anchored proteins. The firsts are associated to tetraspanin-enriched microdomains and the seconds to lipid rafts. Here we report membrane raft involvement in mouse fertilization assessed by cholesterol modulation using methyl-β-cyclodextrin. Cholesterol removal induced: (1 a decrease of the fertilization rate and index; and (2 a delay in the extrusion of the second polar body. Cholesterol repletion recovered the fertilization ability of cholesterol-depleted oocytes, indicating reversibility of these effects. In vivo time-lapse analyses using fluorescent cholesterol permitted to identify the time-point at which the probe is mainly located at the plasma membrane enabling the estimation of the extent of the cholesterol depletion. We confirmed that the mouse oocyte is rich in rafts according to the presence of the raft marker lipid, ganglioside GM1 on the membrane of living oocytes and we identified the coexistence of two types of microdomains, planar rafts and caveolae-like structures, by terms of two differential rafts markers, flotillin-2 and caveolin-1, respectively. Moreover, this is the first report that shows characteristic caveolae-like invaginations in the mouse oocyte identified by electron microscopy. Raft disruption by cholesterol depletion disturbed the subcellular localization of the signal molecule c-Src and the inhibition of Src kinase proteins prevented second polar body extrusion, consistent with a role of Src-related kinases in fertilization via signaling complexes. Our data highlight the functional importance of intact membrane rafts for mouse fertilization and its dependence on cholesterol.

  18. Cholesterol in the rod outer segment: A complex role in a "simple" system.

    Science.gov (United States)

    Albert, Arlene; Alexander, Desiree; Boesze-Battaglia, Kathleen

    2016-09-01

    The rod outer segment (ROS) of retinal photoreceptor cells consists of disk membranes surrounded by the plasma membrane. It is a relatively uncomplicated system in which to investigate cholesterol distribution and its functional consequences in biologically relevant membranes. The light sensitive protein, rhodopsin is the major protein in both membranes, but the lipid compositions are significantly different in the disk and plasma membranes. Cholesterol is high in the ROS plasma membrane. Disk membranes are synthesized at the base of the ROS and are also high in cholesterol. However, cholesterol is rapidly depleted as the disks are apically displaced. During this apical displacement the disk phospholipid fatty acyl chains become progressively more unsaturated, which creates an environment unfavorable to cholesterol. Membrane cholesterol has functional consequences. The high cholesterol found in the plasma membrane and in newly synthesized disks inhibits the activation of rhodopsin. As disks are apically displaced and cholesterol is depleted rhodopsin becomes more responsive to light. This effect of cholesterol on rhodopsin activation has been shown in both native and reconstituted membranes. The modulation of activity can be at least partially explained by the effect of cholesterol on bulk lipid properties. Cholesterol decreases the partial free volume of the hydrocarbon region of the bilayer and thereby inhibits rhodopsin conformational changes required for activation. However, cholesterol binds to rhodopsin and may directly affect the protein also. Furthermore, cholesterol stabilizes rhodopsin to thermal denaturation. The membrane must provide an environment that allows rhodopsin conformational changes required for activation while also stabilizing the protein to thermal denaturation. Cholesterol thus plays a complex role in modulating the activity and stability of rhodopsin, which have implications for other G-protein coupled receptors.

  19. 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.

  20. The effect of dietary rape-seed oil on cholesterol-ester metabolism and cholesterol-ester-hydrolase activity in the rat adrenal.

    Science.gov (United States)

    Beckett, G J; Boyd, G S

    1975-05-06

    The effects of stock diet and stock diet supplemented by olive oil and rape seed on rat adrenal cholesterol ester metabolism have been studied. Rats fed rape seed oil failed to gain weight at the same rate as rats fed olive oil. A prominent feature of the rats fed rape seed oil was an accumulation of high concentrations of cholesterol erucate in the adrenal lipid droplets. When these rats were subjected to an ether stress no percentage decrease in the amount of cholesterol erucate was observed. Adrenal cholesterol ester hydrolase activity was higher in rats fed the olive oil and rape seed oil diets than rats fed the stock diet. In rats fed stock or olive oil diets, a ten-minute ether anaesthesia stress resulted in a two-fold increase in activity of adrenal cholesterol ester hydrolase. Cofactor addition of ATP, cyclic AMP and MgCl-2 in vitro resulted in a stimulation of cholesterol ester hydrolase to a similar activity in both quiescent and ether-stressed rats. By contrast rats fed the rape seed oil diet gave no significant stimulation of cholesterol ester hydrolase activity when given an ether stress or when cofactors were added in vitro. Cholesterol erucate was hydrolysed at only 25% to 30% of the rate of cholesterol oleate in vitro in all groups of animals. Oleic acid added in vitro gave an inhibition of cholesterol ester hydrolase activity in rats fed stock diet while erucic acid activated the enzyme. The accumulation of cholesterol erucate in the adrenal when rats are fed rape seed oil could be due to the reduced ability of cholesterol ester hydrolase to hydrolyse this ester.

  1. [Serum phospholipids and processes of cholesterol esterification in the European North].

    Science.gov (United States)

    Boĭko, E R; Bichkaeva, F A; Tkachev, A V

    2002-01-01

    Lipid profile was studied in blood serum of 146 European northerns (trans-polar Nenets Autonomous district and Archangelsk). Monolayer chromatography was used to determine sphingomyelin (SP), phosphatidyl ethanolamine, phosphatidylcholine (PC), lisophosphatidylcholine, glycerophosphatides and phosphatide acides. The northerns were found to have very low concentrations of blood PC. At the same time, the NAD population have a little higher SP which may play an adaptive role in terms of the cell membrane function. The transpolar natives appear to possess an adaptive mechanism of increasing total cholesterol and reducing cholesterol of high-density lipoproteins, and activation of cholesterol esterification resulting in decrease in the free cholesterol fraction in serum.

  2. 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.

  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. 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.

  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. 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

  7. Trans Fatty Acids, HDL-cholesterol, and Cardiovascular Disease. Effects of Dietary Changes on Vascular Reactivity

    NARCIS (Netherlands)

    Roos, de N.M.; Schouten, E.G.; Katan, M.B.

    2003-01-01

    A high consumption of trans fatty acids increases the risk of cardiovascular disease (CVD). We investigeted whether this increase in risk was due to the decrease in serum HDL-cholesterol by trans fatty acids, because low concentrations of serum HDL-cholesterol also increase risk of CVD. Flow-mediate

  8. LDL cholesterol goals and cardiovascular risk during statin treatment

    DEFF Research Database (Denmark)

    Olsson, Anders G; Lindahl, Christina; Holme, Ingar

    2011-01-01

    We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how...

  9. Modification of Cellular Cholesterol Content Affects Traction Force, Adhesion and Cell Spreading.

    Science.gov (United States)

    Norman, Leann L; Oetama, Ratna J; Dembo, Micah; Byfield, F; Hammer, Daniel A; Levitan, Irena; Aranda-Espinoza, Helim

    2010-06-01

    Cellular cholesterol is a critical component of the plasma membrane, and plays a key role in determining the physical properties of the lipid bilayer, such as elasticity, viscosity, and permeability. Surprisingly, it has been shown that cholesterol depletion increases cell stiffness, not due to plasma membrane stiffening, but rather, due to the interaction between the actin cytoskeleton and the plasma membrane. This indicates that traction stresses of the acto-myosin complex likely increase during cholesterol depletion. Here we use force traction microscopy to quantify the forces individual cells are exerting on the substrate, and total internal reflection fluorescence microscopy as well as interference reflection microscopy to observe cell-substrate adhesion and spreading. We show that single cells depleted of cholesterol produce larger traction forces and have large focal adhesions compared to untreated or cholesterol-enriched cells. Cholesterol depletion also causes a decrease in adhesion area for both single cells and monolayers. Spreading experiments illustrate a decrease in spreading area for cholesterol-depleted cells, and no effect on cholesterol-enriched cells. These results demonstrate that cholesterol plays an important role in controlling and regulating the cell-substrate interactions through the actin-plasma membrane complex, cell-cell adhesion, and spreading.

  10. 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.

  11. Cholesterol efflux and metabolic abnormalities associated with low high-density-lipoprotein-cholesterol and high triglycerides in statin-treated coronary men with low-density lipoprotein-cholesterol <70 mg/dl.

    Science.gov (United States)

    Posadas-Sánchez, Rosalinda; Posadas-Romero, Carlos; Mendoza-Pérez, Enrique; Caracas-Portilla, Nacú Aureo; Cardoso-Saldaña, Guillermo; Medina-Urrutia, Aída; Jorge-Galarza, Esteban; Juárez-Rojas, Juan Gabriel

    2012-03-01

    In 69 statin-treated male coronary patients with low-density lipoprotein cholesterol at goal levels (cholesterol (triglyceride (>150 mg/dl) are associated with dysfunctional HDL particles and abnormal insulin, adiponectin, C-reactive protein serum levels. Thirty-four patients with low HDL cholesterol and high triglyceride (dyslipidemia) and 35 patients with low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride at target levels (normolipidemia) were studied. Twenty healthy men were also studied. High-sensitivity C-reactive protein was measured using immunonephelometry, insulin using a radioimmunometric assay, and total adiponectin by enzyme-linked immunosorbent assay. Cell cholesterol efflux to serum and total isolated HDL was assayed using rat hepatoma Fu5AH cells for scavenger receptor class B type 1-mediated efflux. Compared to the normolipidemia and healthy groups, and after adjustment for age and waist circumference, patients with dyslipidemia showed higher fasting insulin (14, 9.9, and 8.5 μU/ml, respectively), homeostasis model assessment of insulin resistance values (3.4, 2.3, and 1.8, respectively), lower adiponectin concentrations (5.1, 8.1, and 11 μg/ml, respectively), and reduced cholesterol efflux to serum (14%, 15%, and 19%, respectively) and to HDL fractions (4.4%, 4.6%, and 5.6%, respectively) (p cholesterol efflux. In conclusion, the decreased cholesterol efflux and metabolic abnormalities found in the dyslipidemia group may contribute to the residual risk observed in the large statin trials and the higher morbidity and mortality in statin-treated coronary patients with low HDL cholesterol even when attaining low-density lipoprotein cholesterol <70 mg/dl. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Consumption of Japanese Yam Improves Lipid Metabolism in High-Cholesterol Diet-Fed Rats.

    Science.gov (United States)

    Kusano, Yuri; Tsujihara, Nobuko; Masui, Hironori; Kozai, Hana; Takeuchi, Wakako

    2016-01-01

    We investigated the effects of dietary Japanese yam (Dioscorea japonica Thunb.) on lipid metabolism. Male Wistar rats (6 wk old) were fed a high-cholesterol diet for 6 wk and then supplemented with 26% of Japanese yam or 0.5% of its constituent diosgenin for a further 4 wk of high-cholesterol feeding (C6-J4 and C6-D4 groups, respectively). In the C6-J4 group, body weight gains significantly decreased, but skeletal muscle fiber sizes in quadriceps significantly increased compared with the other groups. Furthermore, Japanese yam supplementation resulted in the reduction of triglyceride contents in their liver, quadriceps, and intra-abdominal visceral fat. Diosgenin supplementation resulted in an increase in the numbers of skeletal muscle fibers and decrease in the fat accumulations in liver and of the lipid contents in quadriceps. Although quadriceps cholesterol contents decreased concomitantly with increased serum HDL-cholesterol in both the groups, fecal bile acid, fecal cholesterol contents, and fecal weight were higher in the C6-J4 group than in the C6-D4 group. Meanwhile, we demonstrated that Japanese yam inhibited micellar cholesterol solubility in vitro in a concentration-dependent manner. These results suggest that Japanese yam is more effective than diosgenin in reducing fat accumulation and improving cholesterol metabolism during chronic consumption of a high-cholesterol diet.

  17. Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation.

    Science.gov (United States)

    Nakai, Kuniharu; Tazuma, Susumu; Nishioka, Tomoji; Chayama, Kazuaki

    2003-06-10

    Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the

  18. 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

  19. How Is High Blood Cholesterol Diagnosed?

    Science.gov (United States)

    ... for total and HDL cholesterol does not require fasting. If your total cholesterol is 200 mg/dL ... triglyceride level include: Overweight and obesity Lack of physical activity Cigarette smoking Excessive alcohol use A very high ...

  20. 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 ...

  1. Do You Know Your Cholesterol Levels?

    Science.gov (United States)

    ... 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 ...

  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. Nanoscale Membrane Domain Formation Driven by Cholesterol

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

    2017-01-01

    Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

  5. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.

    Science.gov (United States)

    Gao, Yansong; Zhou, Yulian; Goldstein, Joseph L; Brown, Michael S; Radhakrishnan, Arun

    2017-05-26

    Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells, this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to demonstrate this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualized with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Cholesterol-lowering effect of the mushroom Pleurotus ostreatus in hereditary hypercholesterolemic rats.

    Science.gov (United States)

    Bobek, P; Ginter, E; Jurcovicová, M; Kuniak, L

    1991-01-01

    We studied the effect of the edible mushroom Pleurotus ostreatus (4% in diet containing 1% of cholesterol) on serum and liver lipids in female rats with hereditary enhanced sensitivity to alimentary cholesterol. We found that the consumption of the mushroom-containing diet prevented serum cholesterol increase which was manifested at the end of the 4th week of the experiment. At the end of the 7th week of the experiment the cholesterolemia was lowered by almost 40% as compared with control animals kept on the same diet but without the mushroom. The decrease in serum cholesterol levels is a consequence of the decreased cholesterol concentrations of very-low-density lipoproteins and of low-density lipoproteins.

  7. Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents.

    Science.gov (United States)

    Martin, Mauricio G; Ahmed, Tariq; Korovaichuk, Alejandra; Venero, Cesar; Menchón, Silvia A; Salas, Isabel; Munck, Sebastian; Herreras, Oscar; Balschun, Detlef; Dotti, Carlos G

    2014-05-30

    Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.

  8. Why have total cholesterol levels declined in most developed countries?

    Directory of Open Access Journals (Sweden)

    Ford Earl S

    2011-08-01

    Full Text Available Abstract Background Our paper addresses three major public health issues: cholesterol, statins and policies to prevent cardiovascular disease. Discussion Total cholesterol levels in whole populations have fallen substantially in the USA, UK and most other developed countries. This has greatly contributed to decreases in cardiovascular disease deaths. The evidence identifying diet as the major contributor to these historical falls in cholesterol is powerful and consistent. Large falls occurred before statins were introduced. Additional substantial falls occurred before statins were widely used. Now, up to 14% adults in Western populations currently receive statins for primary prevention. Furthermore, because diet is now only slowly improving, the statin contribution currently appears proportionately larger. Summary In conclusion, diet change explains most of the historical falls in cholesterol. Until very recently, the contribution from statins has been surprisingly modest. Furthermore, many middle income countries may have neither the resources nor the infrastructure for mass statin therapy. Further substantial falls in cholesterol are therefore unlikely to be obtained simply by increased use of statins or dietary advice to individuals if unsupported by the wider environment. This further emphasises the need for more effective structural policies. Regulatory and fiscal interventions could easily eradicate industrial transfats, halve the intake of dietary saturated fat, and subsidise healthier fats.

  9. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Science.gov (United States)

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  10. Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses.

    Science.gov (United States)

    Bajimaya, Shringkhala; Hayashi, Tsuyoshi; Frankl, Tünde; Bryk, Peter; Ward, Brian; Takimoto, Toru

    2017-01-15

    Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV. Mechanistic analysis indicated that depletion of cellular cholesterol reduced cell surface accumulation of envelope glycoproteins and association of viral matrix and nucleocapsids with raft membrane, which resulted in impaired virus budding and release from the cells. These results indicate that cellular cholesterol is required for assembly and formation of type 1 parainfluenza viruses and suggest that cholesterol could be an attractive target for antiviral agents against hPIV1. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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.

  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. 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)...

  14. 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.

  15. Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

    Science.gov (United States)

    2011-01-01

    Background The hypocholesterolemic effects of lactic acid bacteria (LAB) have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of Lactobacillus plantarum 9-41-A and Lactobacillus fermentum M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet. Methods Forty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum 9-41-A or Lactobacillus fermentum M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid deposition were significantly decreased in the LAB-treated groups (p cholesterol and bile acids levels were significantly increased after LAB administration (p cholesterol diet, administration of Lactobacillus plantarum 9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, L. plantarum 9-41-A may play a role in fat metabolism. PMID:21722398

  16. 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

  17. 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.

  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. 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

  20. 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)

  1. 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...

  2. 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…

  3. 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

  4. 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

  5. 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…

  6. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  7. 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.

  8. DPPC-cholesterol phase diagram using coarse-grained Molecular Dynamics simulations.

    Science.gov (United States)

    Wang, Yin; Gkeka, Paraskevi; Fuchs, Julian E; Liedl, Klaus R; Cournia, Zoe

    2016-11-01

    Cholesterol-phospholipid bilayers continue to be the current state of the art in membrane models and serve as representative systems for studying the effect of cholesterol on the cell membrane. As the mixing of different lipid species requires long spatio-temporal scales, coarse-grained models have gained increasing popularity in modeling such membrane systems. In this paper, a systematic study of the MARTINI coarse-grained model for the DPPC-cholesterol binary system has been performed. We construct the phase diagram of DPPC lipid bilayers in the presence of different cholesterol concentrations and at different temperatures using coarse-grained Molecular Dynamics (MD) simulations with the MARTINI force field. The phase diagram based on the condensation effect is directly comparable to available experimental data and demonstrates qualitative agreement over all cholesterol concentrations. Self-assembled bilayers quantitatively reproduce experimental observables, such as lateral diffusion of lipids, electron density, area per lipid and lipid order parameters. The phase diagram of the DPPC-cholesterol binary system also reveals the profound effect of cholesterol on the physical properties of phospholipid bilayers such lipid order, diffusion, and fluidity. Cholesterol induces the liquid-ordered phase, which increases the fluidity of the phospholipid hydrocarbon chains above the gel to liquid-crystalline phase transition temperature and decreases it below the phase transition. The present study suggests that the MARTINI force field can be successfully used to obtain molecular level insights into cholesterol-DPPC model membranes. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

    Science.gov (United States)

    Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

    2014-01-01

    High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

  10. Cholesterol influences potassium currents in inner hair cells isolated from guinea pig cochlea.

    Science.gov (United States)

    Kimitsuki, Takashi

    2017-02-01

    There is a correlation between serum hyperlipidemia and hearing loss. Cholesterol is an integral component of the cell membrane and regulates the activity of ion channels in the lipid bilayer. The aim of this study was to investigate the effects of cholesterol on the potassium currents in IHCs by using the cholesterol-depleting drug, MβCD, and water-soluble cholesterol. IHCs were acutely isolated from a mature guinea-pig cochlea and potassium currents were recorded. MβCD and water-soluble cholesterol were applied to IHCs under pressure puff pipettes. IHCs showed outwardly rectifying currents (IK,f and IK,s) in response to depolarizing voltage pulses, with only a slight inward current (IK,n) when hyperpolarized. In 10mM MβCD solutions, the amplitude of outward K currents reversely decreased; however, fast activation kinetics was preserved. In contrast, in solution of 1mM water-soluble cholesterol, the amplitude of outward K currents reversely increased. At the membrane potential of +110mV, relative conductances were 0.87±0.07 and 1.18±0.11 in MβCD solutions and cholesterol solutions, respectively. The amplitude of K currents in isolated IHCs was reversely changed by cholesterol-depleting drug and water-soluble cholesterol. These results demonstrated the possibility of the involvement of IHC function in hyperlipidemia-induced inner ear disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content.

    Directory of Open Access Journals (Sweden)

    Hanna Appelqvist

    Full Text Available Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1 protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2, which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determineD the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

  12. 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.

  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. The effect of defatted cocoa powder on cholesterol-induced changes of serum lipids in rats

    Science.gov (United States)

    Ahmad, Mousa Numan; Amr, Amira Mohammad

    2017-06-05

    Cocoa has been known for many health benefits, but its lipid-lowering activity still remains unresolved. To investigate effects of varying amounts of defatted cocoa on serum lipids in cholesterol-fed rats. Forty-eight male Sprague-Dawley rats were randomly assigned into four cholesterol-free (control) and four cholesterol-supplemented (experimental) diets containing 0, 1, 2 or 3% defatted cocoa (DC) and given ad libitumto the rats for ten weeks. Serum total cholesterol (TC), low- and very low-density lipoprotein cholesterol (LDL-C and VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were quantified, atherogenic index (AI) was calculated, and other biological parameters were assessed. Food intake and body weight did not respond to DC. Compared to 0% DC, 3% DC had the most prominent effect on serum lipids inducing significant fall in LDL-C and TG, and rise in TC/TG in cholesterol-deprived rats, and increase in VLDL-C and AI, and decrease in HDL-C in cholesterol-fed rats. Compared to cholesterol-deprived rats, 3% DC caused significant rise in VLDL-C, AI and TC/TG, and fall in TG in cholesterol-fed rats. This lipid-modifying effect was markedly substantiated by corresponding linear trend responses to DC. Differences in lipid variables of rats fed on DC diets were less evident. Results suggest that, in contrast to cholesterol-free situations, defatted cocoa is seemingly incapable of counteracting the atherogenic effect of cholesterol in rats, perhaps in an interaction that is likely to have clinical implications in cardiometabolic conditions.

  15. Fish oil replacement in current aquaculture feed: is cholesterol a hidden treasure for fish nutrition?

    Science.gov (United States)

    Norambuena, Fernando; Lewis, Michael; Hamid, Noor Khalidah Abdul; Hermon, Karen; Donald, John A; Turchini, Giovanni M

    2013-01-01

    Teleost fish, as with all vertebrates, are capable of synthesizing cholesterol and as such have no dietary requirement for it. Thus, limited research has addressed the potential effects of dietary cholesterol in fish, even if fish meal and fish oil are increasingly replaced by vegetable alternatives in modern aquafeeds, resulting in progressively reduced dietary cholesterol content. The objective of this study was to determine if dietary cholesterol fortification in a vegetable oil-based diet can manifest any effects on growth and feed utilization performance in the salmonid fish, the rainbow trout. In addition, given a series of studies in mammals have shown that dietary cholesterol can directly affect the fatty acid metabolism, the apparent in vivo fatty acid metabolism of fish fed the experimental diets was assessed. Triplicate groups of juvenile fish were fed one of two identical vegetable oil-based diets, with additional cholesterol fortification (high cholesterol; H-Chol) or without (low cholesterol; L-Chol), for 12 weeks. No effects were observed on growth and feed efficiency, however, in fish fed H-Col no biosynthesis of cholesterol, and a remarkably decreased apparent in vivo fatty acid β-oxidation were recorded, whilst in L-Chol fed fish, cholesterol was abundantly biosynthesised and an increased apparent in vivo fatty acid β-oxidation was observed. Only minor effects were observed on the activity of stearyl-CoA desaturase, but a significant increase was observed for both the transcription rate in liver and the apparent in vivo activity of the fatty acid Δ-6 desaturase and elongase, with increasing dietary cholesterol. This study showed that the possible effects of reduced dietary cholesterol in current aquafeeds can be significant and warrant future investigations.

  16. 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.

  17. 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.

  18. Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition.

    Science.gov (United States)

    Alqahtani, Saeed; Qosa, Hisham; Primeaux, Brian; Kaddoumi, Amal

    2015-09-05

    The known mechanism by which orlistat decreases the absorption of dietary cholesterol is by inhibition of intestinal lipases. The aim of this study was to investigate the ability of orlistat to limit cholesterol absorption by inhibition of the cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) as another mechanism of action. In situ rat intestinal perfusion studies were conducted to study the effect of orlistat on jejunal cholesterol absorption. Inhibition kinetic parameters were calculated from in vitro inhibition studies using Caco2 and NPC1L1 transfected cell lines. The in situ studies demonstrated that intestinal perfusion of orlistat (100µM) was able to reduce cholesterol absorption by three-fold when compared to control (i.e. in the absence of orlistat, Pabsorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein.

  19. HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C > A) and modified by glucocorticoid treatment

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, Andre P.

    2010-01-01

    Objective: GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is

  20. 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

  1. 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....

  2. Cholesterol-Lowering Supplements: Lower Your Numbers without Prescription Medication

    Science.gov (United States)

    ... extract May reduce total cholesterol and low-density lipoprotein (LDL), or "bad," cholesterol May cause gas or ... Niacin May lower LDL cholesterol, improve high-density lipoprotein (HDL), or "good" cholesterol May cause headache, nausea, ...

  3. 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

  4. 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

  5. Cholesterol Down-Regulates BK Channels Stably Expressed in HEK 293 Cells

    Science.gov (United States)

    Deng, Xiu-Ling; Sun, Hai-Ying; Li, Gui-Rong

    2013-01-01

    Cholesterol is one of the major lipid components of the plasma membrane in mammalian cells and is involved in the regulation of a number of ion channels. The present study investigates how large conductance Ca2+-activated K+ (BK) channels are regulated by membrane cholesterol in BK-HEK 293 cells expressing both the α-subunit hKCa1.1 and the auxiliary β1-subunit or in hKCa1.1-HEK 293 cells expressing only the α-subunit hKCa1.1 using approaches of electrophysiology, molecular biology, and immunocytochemistry. Membrane cholesterol was depleted in these cells with methyl-β-cyclodextrin (MβCD), and enriched with cholesterol-saturated MβCD (MβCD-cholesterol) or low-density lipoprotein (LDL). We found that BK current density was decreased by cholesterol enrichment in BK-HEK 293 cells, with a reduced expression of KCa1.1 protein, but not the β1-subunit protein. This effect was fully countered by the proteasome inhibitor lactacystin or the lysosome function inhibitor bafilomycin A1. Interestingly, in hKCa1.1-HEK 293 cells, the current density was not affected by cholesterol enrichment, but directly decreased by MβCD, suggesting that the down-regulation of BK channels by cholesterol depends on the auxiliary β1-subunit. The reduced KCa1.1 channel protein expression was also observed in cultured human coronary artery smooth muscle cells with cholesterol enrichment using MβCD-cholesterol or LDL. These results demonstrate the novel information that cholesterol down-regulates BK channels by reducing KCa1.1 protein expression via increasing the channel protein degradation, and the effect is dependent on the auxiliary β1-subunit. PMID:24260325

  6. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

    Directory of Open Access Journals (Sweden)

    Zahedi Mujawar

    2006-10-01

    Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

  8. Peptide mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 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.

  10. 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.

  11. 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....

  12. Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse.

    Science.gov (United States)

    Valasek, Mark A; Clarke, Stephen L; Repa, Joyce J

    2007-12-01

    Fibrates, including fenofibrate, exert their biological effects by binding peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily of ligand-activated transcription factors. Treatment with PPARalpha agonists enhances fatty acid oxidation, decreases plasma triglycerides, and may promote reverse cholesterol transport. In addition, fibrate administration can reduce intestinal cholesterol absorption in patients, although the molecular mechanism for this effect is unknown. Because Niemann-Pick C1-Like 1 (NPC1L1) is already known to be a critical protein for cholesterol absorption, we hypothesized that fenofibrate might modulate NPC1L1 expression to alter intestinal cholesterol transport. Here, we find that fenofibrate-treated wild-type mice have decreased fractional cholesterol absorption (35-47% decrease) and increased fecal neutral sterol excretion (51-83% increase), which correspond to decreased expression of NPC1L1 mRNA and protein (38-66% decrease) in the proximal small intestine. These effects of fenofibrate are dependent on PPARalpha, as Ppar alpha-knockout mice fail to respond like wild-type littermates. Fenofibrate affects the ezetimibe-sensitive pathway and retains the ability to decrease cholesterol absorption and NPC1L1 mRNA expression in chow-fed liver X receptor alpha/beta-double-knockout mice and high-cholesterol- or cholic acid-fed wild-type mice. These data demonstrate that fenofibrate specifically acts via PPARalpha to decrease cholesterol absorption at the level of intestinal NPC1L1 expression.

  13. Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study

    Directory of Open Access Journals (Sweden)

    Maarit Hallikainen

    2013-01-01

    Full Text Available To evaluate whether parameters of obstructive sleep apnoea (OSA associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N=23 or to control group (N=18 with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols and synthesis (cholestenol, desmosterol, and lathosterol at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 was associated with serum campesterol (P<0.05 and inversely with desmosterol ratios (P<0.001 independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR. Apnoea-hypopnoea index (AHI was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P<0.05. In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.

  14. 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.

  15. 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.

  16. 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.

  17. Effects of tegaserod on bile composition and hepatic secretion in Richardson ground squirrels on an enriched cholesterol diet

    Directory of Open Access Journals (Sweden)

    Pfannkuche Hans-Juergen

    2006-06-01

    Full Text Available Abstract Background Tegaserod is effective in treating IBS patients with constipation, and does not alter gallbladder motility in healthy individuals or in patients with IBS. However, it is not known if tegaserod affects the biliary tract in gallstone disease, so to this end the effects of tegaserod on bile composition and hepatic secretion of Richardson ground squirrels maintained on an enriched cholesterol diet were examined. Results Animals were fed either a control (0.03% or enriched (1% cholesterol diet for 28 days, and treated s.c. with tegaserod (0.1 mg/kg BID or vehicle. Bile flow, bile acid, phospholipids and cholesterol secretion were measured with standard methods. Tegaserod treatment or enriched cholesterol diet, alone or combination, did not alter body or liver weights. The enriched cholesterol diet increased cholesterol saturation index (CSI, cholesterol concentrations in gallbladder and hepatic duct bile by ~50% and decreased bile acids in gallbladder bile by 17%. Tegaserod treatment reversed these cholesterol-induced changes. None of the treatments, drug or diet, altered fasting gallbladder volume, bile flow and bile salts or phospholipid secretion in normal diet and cholesterol-fed animals. However, tegaserod treatment prevented the decreases in bile acid pool size and cycling frequency caused by the enriched cholesterol diet, consequent to re-establishing normal bile acid to concentrations in the gall bladder. Tegaserod had no effect on these parameters with normal diet animals. Conclusion Tegaserod treatment results in increased enterohepatic cycling and lowers cholesterol saturation in the bile of cholesterol-fed animals. These effects would decrease conditions favorable to cholesterol gallstone formation.

  18. 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.

  19. Effect of Cholesterol Removal Processing Using β-Cyclodextrin on Main Components of Milk

    Directory of Open Access Journals (Sweden)

    A. M. Maskooki

    2013-01-01

    Full Text Available Various concentrations (0%, 0.5%, 1% and 1.5% of β-CD were mixed with different fat contents (1%, 2.5% and 3% of raw (unhomogenized and homogenized milk at two mixing temperatures of 8 and 20°C. The cholesterol residue, fat, protein, lactose, solid nonfat (SNF, density, and ash content of milk were measured for each treatment. The results statistically analysed and showed that the cholesterol content of milk remarkably decreased as the β-CD was increased particularly in homogenized milk at 20°C. However, the reduction rate of cholesterol was decreased when extra β-CD was added due to its intermolecular reactions. The maximum cholesterol reduction was achieved at the level of 1% β-CD. The fat content, SNF, protein, lactose, and density content were decreased with increasing β-CD whereas it did not affect ash content.

  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. Hypolipidemic effects of aqueous extract of Acalypha capitata leaves in rats fed on high cholesterol diet

    Institute of Scientific and Technical Information of China (English)

    Nnodim Johnkennedy; Emejulu Adamma; Nwadike Constance Nnedimma

    2011-01-01

    Objective:To evaluate the hypolipidemic effects of aqueous extract of Acalypha capitata (A. capitata) leaves in rats fed on high cholesterol diet. Methods:Cholesterol diet was administered to Wistar rats at a dose of 40 mg per 0.2 mL 3 times daily for 14 days while the control received distilled water. These animals were treated with extract of A. capitata at doses of 100 and 200 mg/kg. Lipid profiles were observed and compared. Results:Administration of A. capitata caused significant decrease in cholesterol, triglyceride and low density lipoprotein-cholesterol when compared with the control (P<0.05) which was dose dependent. Also, it was observed that high density lipoprotein-cholesterol was significantly increased when compared with the control. Conclusions:This observation suggests that the leaf extract of A. capitata could probably serve as a potential natural product for treatment of hyperlipidaemia.

  2. Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis.

    Science.gov (United States)

    Lu, Jun; Zheng, Yuan-Lin; Wu, Dong-Mei; Sun, Dong-Xu; Shan, Qun; Fan, Shao-Hua

    2006-12-11

    Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Copper treatment alone showed no significant learning and memory impairments in behavioral tasks. However, copper-induced neurotoxicity was significantly increased in mice given elevated-cholesterol diet. Trace amounts of copper decreased the activity of SOD and increased the level of malondialdehyde (MDA) in the brain of cholesterol-fed mouse. Copper also caused an increase in amyloid precursor protein (APP) mRNA level and the activation of caspase-3 in the brain of cholesterol-fed mice. The apoptosis-induced nuclear DNA fragmentation was detected in the brain of those mice by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling staining. These findings suggest that trace amounts of copper induce neurotoxicity in cholesterol-fed mice through apoptosis caused by oxidative stress.

  3. Regulation of the high-affinity choline transporter activity and trafficking by its association with cholesterol-rich lipid rafts.

    Science.gov (United States)

    Cuddy, Leah K; Winick-Ng, Warren; Rylett, Rebecca Jane

    2014-03-01

    The sodium-coupled, hemicholinium-3-sensitive, high-affinity choline transporter (CHT) is responsible for transport of choline into cholinergic nerve terminals from the synaptic cleft following acetylcholine release and hydrolysis. In this study, we address regulation of CHT function by plasma membrane cholesterol. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts in both SH-SY5Y cells and nerve terminals from mouse forebrain. Treatment of SH-SY5Y cells expressing rat CHT with filipin, methyl-β-cyclodextrin (MβC) or cholesterol oxidase significantly decreased choline uptake. In contrast, CHT activity was increased by addition of cholesterol to membranes using cholesterol-saturated MβC. Kinetic analysis of binding of [(3)H]hemicholinium-3 to CHT revealed that reducing membrane cholesterol with MβC decreased both the apparent binding affinity (KD) and maximum number of binding sites (Bmax ); this was confirmed by decreased plasma membrane CHT protein in lipid rafts in cell surface protein biotinylation assays. Finally, the loss of cell surface CHT associated with lipid raft disruption was not because of changes in CHT internalization. In summary, we provide evidence that CHT association with cholesterol-rich rafts is critical for transporter function and localization. Alterations in plasma membrane cholesterol cholinergic nerve terminals could diminish cholinergic transmission by reducing choline availability for acetylcholine synthesis. The sodium-coupled choline transporter CHT moves choline into cholinergic nerve terminals to serve as substrate for acetylcholine synthesis. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts, and decreasing membrane cholesterol significantly reduces both choline uptake activity and cell surface CHT protein levels. CHT association with cholesterol-rich rafts is critical for its function, and alterations in plasma membrane cholesterol could diminish cholinergic

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

    Directory of Open Access Journals (Sweden)

    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.

  5. The Effect of Cholesterol on the Binding and Insertion of Cytochrome b5 into Liposomes of Phosphatidylcholines

    Science.gov (United States)

    1993-09-30

    mole percent, cholesterol decreases and broadens the sharp endothermic phase transition in multi lamellar veicles of DPPC (Estep et al., 1978), DHPC ...may similarly converge (i.e . the Ld+Lo immiscibility region narrows) above Tc in the POPC/cholesterol system. In the DHPC /cholesterol phase diagram...composition and temperature dependent. Particularly, the DHPC /cholescerol phase diagram shows that at about 37·C a single liquid-disordered phase

  6. 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.

  7. MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

    Directory of Open Access Journals (Sweden)

    Elisa Balboa

    2017-08-01

    Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

  8. MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content.

    Science.gov (United States)

    Balboa, Elisa; Castro, Juan; Pinochet, María-José; Cancino, Gonzalo I; Matías, Nuria; José Sáez, Pablo; Martínez, Alexis; Álvarez, Alejandra R; Garcia-Ruiz, Carmen; Fernandez-Checa, José C; Zanlungo, Silvana

    2017-08-01

    MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH) levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

    Science.gov (United States)

    Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M

    2017-08-01

    Background: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function.Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes.Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants (n = 48) and in normal-weight (body mass index: HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL (P HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230. © 2017 American Society for Nutrition.

  10. 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

  11. Supplementation with Aspergillus oryzae-fermented kochujang lowers serum cholesterol in subjects with hyperlipidemia.

    Science.gov (United States)

    Lim, Ji-Hee; Jung, Eun-Soo; Choi, Eun-Kyung; Jeong, Do-Yeoun; Jo, Seung-Wha; Jin, Jung-Hyun; Lee, Jung-Mi; Park, Byung-Hyun; Chae, Soo-Wan

    2015-06-01

    Kochujang, a traditional fermented red pepper paste, is known for its hypocholesterolemic effect; however, these studies used non-commercial preparations of kochujang. In this study, we examined whether commercially-made kochujang in which Aspergillus oryzae (also known as koji) was used as a microorganism for fermentation has the same cholesterol-lowering effects. Hyperlipidemic subjects (based upon criteria of 110 ∼ 190 mg/dL LDL cholesterol or 200 ∼ 260 mg/dL total cholesterol) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 30 subjects were randomly divided into either the kochujang (n = 15) or placebo (n = 15) group. All subjects ingested either the kochujang pill (34.5 g/d) or a placebo three times daily during meals for 12 weeks. Outcomes included measurements of efficacy (total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride) and safety (adverse events, laboratory tests, electrocardiogram, and vital signs). In the kochujang-supplemented group, subjects' total cholesterol level significantly decreased (from 215.5 ± 16.1 mg/dL to 194.5 ± 25.4 mg/dL, p = 0.001). LDL-C cholesterol levels were also decreased by kochujang supplementation (from 133.6 ± 14.8 mg/dL to 113.5 ± 23.1 mg/dL); however no significant difference was seen between groups (p = 0.074). There were no statistically significant differences in HDL-cholesterol and triglyceride levels between the supplemented and non-supplemented groups. None of the subjects complained of any adverse effects. These results indicate that A. oryzae-fermented kochujang elicits a significant hypocholesterolemic effect and might be useful for improving blood cholesterol levels in subjects at high risk for cardiovascular disease. NCT01865370. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  12. Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice.

    Science.gov (United States)

    Shubha, Malenahalli C; Reddy, Raghunatha R L; Srinivasan, Krishnapura

    2011-04-01

    Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

  13. Omega 3 fatty acids promote macrophage reverse cholesterol transport in hamster fed high fat diet.

    Directory of Open Access Journals (Sweden)

    Fatima Kasbi Chadli

    Full Text Available The aim of this study was to investigate macrophage reverse cholesterol transport (RCT in hamster, a CETP-expressing species, fed omega 3 fatty acids (ω3PUFA supplemented high fat diet (HFD. Three groups of hamsters (n = 6/group were studied for 20 weeks: 1 control diet: Control, 2 HFD group: HF and 3 HFD group supplemented with ω3PUFA (EPA and DHA: HFω3. In vivo macrophage-to-feces RCT was assessed after an intraperitoneal injection of (3H-cholesterol-labelled hamster primary macrophages. Compared to Control, HF presented significant (p<0.05 increase in body weight, plasma TG (p<0.01 and cholesterol (p<0.001 with an increase in VLDL TG and in VLDL and LDL cholesterol (p<0.001. Compared to HF, HFω3 presented significant decrease in body weight. HFω3 showed less plasma TG (p<0.001 and cholesterol (p<0.001 related to a decrease in VLDL TG and HDL cholesterol respectively and higher LCAT activity (p<0.05 compared to HF. HFω3 showed a higher fecal bile acid excretion (p<0.05 compared to Control and HF groups and higher fecal cholesterol excretion (p<0.05 compared to HF. This increase was related to higher gene expression of ABCG5, ABCA1 and SR-B1 in HFω3 compared to Control and HF groups (<0.05 and in ABCG1 and CYP7A1 compared to HF group (p<0.05. A higher plasma efflux capacity was also measured in HFω3 using (3H- cholesterol labeled Fu5AH cells. In conclusion, EPA and DHA supplementation improved macrophage to feces reverse cholesterol transport in hamster fed HFD. This change was related to the higher cholesterol and fecal bile acids excretion and to the activation of major genes involved in RCT.

  14. Decreased PCSK9 expression in human hepatocellular carcinoma

    OpenAIRE

    2015-01-01

    Background The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. Methods Thirty-nine...

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

    Directory of Open Access Journals (Sweden)

    Yuguang Lin

    2011-01-01

    Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

  18. Free energy landscapes of sodium ions bound to DMPC-cholesterol membrane surfaces at infinite dilution.

    Science.gov (United States)

    Yang, Jing; Bonomi, Massimiliano; Calero, Carles; Martí, Jordi

    2016-04-07

    Exploring the free energy landscapes of metal cations on phospholipid membrane surfaces is important for the understanding of chemical and biological processes in cellular environments. Using metadynamics simulations we have performed systematic free energy calculations of sodium cations bound to DMPC phospholipid membranes with cholesterol concentration varying between 0% (cholesterol-free) and 50% (cholesterol-rich) at infinite dilution. The resulting free energy landscapes reveal the competition between binding of sodium to water and to lipid head groups. Moreover, the binding competitiveness of lipid head groups is diminished by cholesterol contents. As cholesterol concentration increases, the ionic affinity to membranes decreases. When cholesterol concentration is greater than 30%, the ionic binding is significantly reduced, which coincides with the phase transition point of DMPC-cholesterol membranes from a liquid-disordered phase to a liquid-ordered phase. We have also evaluated the contributions of different lipid head groups to the binding free energy separately. The DMPC's carbonyl group is the most favorable binding site for sodium, followed by DMPC's phosphate group and then the hydroxyl group of cholesterol.

  19. 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.

  20. 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.

  1. 2-Heptyl-Formononetin Increases Cholesterol and Induces Hepatic Steatosis in Mice

    Science.gov (United States)

    Andersen, Charlotte; Schjoldager, Janne G.; Tortzen, Christian G.; Vegge, Andreas; Hufeldt, Majbritt R.; Skaanild, Mette T.; Vogensen, Finn K.; Kristiansen, Karsten; Hansen, Axel K.; Nielsen, John

    2013-01-01

    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. PMID:23738334

  2. 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.

  3. 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.

  4. 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

  5. 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...

  6. 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 ...

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

    Science.gov (United States)

    Bajimaya, Shringkhala; Frankl, Tünde; Hayashi, Tsuyoshi; Takimoto, Toru

    2017-10-01

    Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs

    Directory of Open Access Journals (Sweden)

    Hajjaj H

    2004-02-01

    Full Text Available Abstract Introduction There has been renewed interest in mushroom medicinal properties. We studied cholesterol lowering properties of Ganoderma lucidum (Gl, a renowned medicinal species. Results Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC 9.8%, and HDL 11.2%. Gl (2.5 and 5% had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%, respectively (P Conclusions Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol-lowering foods and medicines containing Gl are envisioned.

  13. 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.

  14. 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...

  15. High Density Lipoproteins and Arteriosclerosis: Role of Cholesterol Efflux and Reverse Cholesterol Transport

    National Research Council Canada - National Science Library

    von Eckardstein, Arnold; Nofer, Jerzy Roch; Assmann, Gerd

    2001-01-01

    Abstract—High density lipoprotein (HDL) cholesterol is an important risk factor for coronary heart disease, and HDL exerts various potentially antiatherogenic properties, including the mediation of reverse transport of cholesterol...

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

    Science.gov (United States)

    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.

  17. Oxidised LDL, HDL cholesterol, LDL cholesterol levels in patients of coronary artery disease

    OpenAIRE

    Ghosh, Joya; Mishra, T.K.; Rao, Y. N.; S K Aggarwal

    2006-01-01

    Coronary artery disease is a major cause of morbidity and has various risk factors. Lipid profile i.e. low HDL-cholesterol, high LDL cholesterol, high total cholesterol, high triglycerides playing important role in its causation. Recently interest has been shown in the oxidized fraction of LDL as one of the risk factors. In the present study 60 age and sex matched normal healthy individuals were taken as controls and 60 patients of CAD were taken. Cholesterol was measured by enzymatic method,...

  18. 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.

  19. Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein-Mediated Reverse Cholesterol Transport

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    2011-01-01

    Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall macrophage-to-fe

  20. Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

    NARCIS (Netherlands)

    Kühnast, S.; Louwe, M.C.; Heemskerk, M.M.; Pieterman, E.J.; Klinken, J.B. van; Berg, S.A.A. van den; Smit, J.W.A.; Havekes, L.M.; Rensen, P.C.N.; Hoorn, J.W.A. van der; Princen, H.M.G.; Jukema, J.W.

    2013-01-01

    Objective:Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional benefi

  1. Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

    NARCIS (Netherlands)

    Kuhnast, S.; Louwe, M.C.; Heemskerk, M.M.; Pieterman, E.J.; Klinken, J.B. van; Berg, S.A. van den; Smit, J.W.A.; Havekes, L.M.; Rensen, P.C.; Hoorn, J.W. van der; Princen, H.M.; Jukema, J.W.

    2013-01-01

    OBJECTIVE: Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional benef

  2. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial

    Science.gov (United States)

    Matthan, Nirupa R.; Resteghini, Nancy; Robertson, Michele; Ford, Ian; Shepherd, James; Packard, Chris; Buckley, Brendan M.; Jukema, J. Wouter; Lichtenstein, Alice H.; Schaefer, Ernst J.

    2010-01-01

    Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences circulating cholesterol concentrations and subsequent coronary heart disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in cholesterol biosynthesis and is efficacious in lowering CHD events and mortality. Nonetheless, CHD events still occur in some treated patients. To address differences in outcome during pravastatin therapy (40 mg/day), plasma markers of cholesterol synthesis (desmosterol, lathosterol) and fractional cholesterol absorption (campesterol, sitosterol) were measured, baseline and on treatment, in the Prospective Study of Pravastatin in the Elderly at Risk trial participants with (cases, n = 223) and without (controls, n = 257) a CHD event. Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls. Decreased concentrations of the cholesterol synthesis markers desmosterol (−12% and −11%) and lathosterol (−50% and −56%) and increased concentrations of the cholesterol absorption markers campesterol (48% and 51%) and sitosterol (25% and 26%) were observed on treatment, but the magnitude of change was similar between cases and controls. These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption. The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment. PMID:19578163

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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.

    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. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

    DEFF Research Database (Denmark)

    Garbarino, J.; Pan, M. H.; Chin, H. F.

    2012-01-01

    STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the non-vesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using...... small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...

  10. Identification of a binding motif in the S5 helix that confers cholesterol sensitivity to the TRPV1 ion channel.

    Science.gov (United States)

    Picazo-Juárez, Giovanni; Romero-Suárez, Silvina; Nieto-Posadas, Andrés; Llorente, Itzel; Jara-Oseguera, Andrés; Briggs, Margaret; McIntosh, Thomas J; Simon, Sidney A; Ladrón-de-Guevara, Ernesto; Islas, León D; Rosenbaum, Tamara

    2011-07-15

    The TRPV1 ion channel serves as an integrator of noxious stimuli with its activation linked to pain and neurogenic inflammation. Cholesterol, a major component of cell membranes, modifies the function of several types of ion channels. Here, using measurements of capsaicin-activated currents in excised patches from TRPV1-expressing HEK cells, we show that enrichment with cholesterol, but not its diastereoisomer epicholesterol, markedly decreased wild-type rat TRPV1 currents. Substitutions in the S5 helix, rTRPV1-R579D, and rTRPV1-F582Q, decreased this cholesterol response and rTRPV1-L585I was insensitive to cholesterol addition. Two human TRPV1 variants, with different amino acids at position 585, had different responses to cholesterol with hTRPV1-Ile(585) being insensitive to this molecule. However, hTRPV1-I585L was inhibited by cholesterol addition similar to rTRPV1 with the same S5 sequence. In the absence of capsaicin, cholesterol enrichment also inhibited TRPV1 currents induced by elevated temperature and voltage. These data suggest that there is a cholesterol-binding site in TRPV1 and that the functions of TRPV1 depend on the genetic variant and membrane cholesterol content.

  11. 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.

  12. 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

  13. 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...

  14. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  15. 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

  16. 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

  17. New CETP inhibitor K-312 reduces PCSK9 expression: a potential effect on LDL cholesterol metabolism.

    Science.gov (United States)

    Miyosawa, Katsutoshi; Watanabe, Yuichiro; Murakami, Kentaro; Murakami, Takeshi; Shibata, Haruki; Iwashita, Masaya; Yamazaki, Hiroyuki; Yamazaki, Koichi; Ohgiya, Tadaaki; Shibuya, Kimiyuki; Mizuno, Ken; Tanabe, Sohei; Singh, Sasha A; Aikawa, Masanori

    2015-07-15

    Despite significant reduction of cardiovascular events by statin treatment, substantial residual risk persists, driving emerging needs for the development of new therapies. We identified a novel cholesteryl ester transfer protein (CETP) inhibitor, K-312, that raises HDL and lowers LDL cholesterol levels in animals. K-312 also suppresses hepatocyte expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a molecule that increases LDL cholesterol. We explored the underlying mechanism for the reduction of PCSK9 expression by K-312. K-312 inhibited in vitro human plasma CETP activity (IC50; 0.06 μM). Administration of K-312 to cholesterol-fed New Zealand White rabbits for 18 wk raised HDL cholesterol, decreased LDL cholesterol, and attenuated aortic atherosclerosis. Our search for additional beneficial characteristics of this compound revealed that K-312 decreases PCSK9 expression in human primary hepatocytes and in the human hepatoma cell line HepG2. siRNA silencing of CETP in HepG2 did not compromise the suppression of PCSK9 by K-312, suggesting a mechanism independent of CETP. In HepG2 cells, K-312 treatment decreased the active forms of sterol regulatory element-binding proteins (SREBP-1 and -2) that regulate promoter activity of PCSK9. Chromatin immunoprecipitation assays demonstrated that K-312 decreased the occupancy of SREBP-1 and SREBP-2 on the sterol regulatory element of the PCSK9 promoter. PCSK9 protein levels decreased by K-312 treatment in the circulating blood of cholesterol-fed rabbits, as determined by two independent mass spectrometry approaches, including the recently developed, highly sensitive parallel reaction monitoring method. New CETP inhibitor K-312 decreases LDL cholesterol and PCSK9 levels, serving as a new therapy for dyslipidemia and cardiovascular disease.

  18. 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.

  19. 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...

  20. 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...

  1. Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

    Directory of Open Access Journals (Sweden)

    Liu Xiao-Wei

    2011-07-01

    Full Text Available Abstract Background The hypocholesterolemic effects of lactic acid bacteria (LAB have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of Lactobacillus plantarum 9-41-A and Lactobacillus fermentum M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet. Methods Forty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum 9-41-A or Lactobacillus fermentum M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p Lactobacillus and Bifidobacterium colonies were increased while Escherichia coli colonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration of Lactobacillus plantarum 9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p Conclusions This study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, L. plantarum 9-41-A may play a role in fat metabolism.

  2. Secular trends in cholesterol lipoproteins and triglycerides and prevalence of dyslipidemias in an urban Indian population.

    Science.gov (United States)

    Gupta, Rajeev; Guptha, Soneil; Agrawal, Aachu; Kaul, Vijay; Gaur, Kiran; Gupta, Vijay P

    2008-10-24

    .5 +/- 39, 2-stage least-squares regression R = 0.11, p cholesterol (106.2 +/- 40, 127.6 +/- 39, 122.6 +/- 44, 119.2 +/- 31, R = 0.11, p cholesterol (131.3 +/- 43, 156.4 +/- 43, 150.1 +/- 41, 150.9 +/- 32, R = 0.12, p cholesterol (25.1 +/- 11, 28.9 +/- 14, 26.0 +/- 11, 31.7 +/- 14, R = 0.06, p = 0.001), total:HDL cholesterol ratio (4.26 +/- 1.3, 5.18 +/- 1.7, 5.21 +/- 1.7, 4.69 +/- 1.2, R = 0.10, p triglycerides (125.6 +/- 53, 144.5 +/- 71, 130.1 +/- 57, 158.7 +/- 72, R = 0.06, p = 0.001) and decrease in HDL cholesterol (43.6 +/- 14, 39.7 +/- 8, 37.3 +/- 6, 42.5 +/- 6, R = 0.04, p = 0.027). Trends in age-adjusted prevalence (%) of dyslipidemias in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed insignificant changes in high total cholesterol (26.3, 35.1, 25.6, 26.0, linear curve-estimation coefficient multiple R = 0.034), high LDL cholesterol > or = 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol cholesterol (23.0, 33.5, 27.4, 26.6, R = 0.026), high remnant cholesterol (40.1, 40.3, 30.1, 60.6, R = 0.143), high total:HDL cholesterol ratio > or = 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and > or = 4.0 (58.6, 72.5, 70.1, 62.0, R = 0.006), and high triglycerides (25.7, 28.2, 17.5, 34.2, R = 0.047). Greater correlation of increasing non-HDL cholesterol, remnant cholesterol, triglycerides and total:HDL cholesterol ratio was observed with increasing truncal obesity than generalized obesity (two-line regression analysis p cholesterol, and triglycerides and decline in HDL cholesterol levels. Prevalence of subjects with high total cholesterol did not change significantly while those with high non-HDL cholesterol, cholesterol remnants, triglycerides and total-HDL cholesterol ratio increased. Increasing dyslipidemias correlate significantly with increasing truncal obesity and obesity.

  3. High Blood Cholesterol: What You Need to Know

    Science.gov (United States)

    ... 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 ...

  4. 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 ...

  5. Cholesterol transport via ABCA1: new insights from solid-phase binding assay.

    Science.gov (United States)

    Reboul, Emmanuelle; Dyka, Frank M; Quazi, Faraz; Molday, Robert S

    2013-04-01

    It is now well established that the ATP-binding cassette transporter A1 (ABCA1) plays a pivotal role in HDL metabolism, reverse cholesterol transport and net efflux of cellular cholesterol and phospholipids. We aimed to resolve some uncertainties related to the putative function of ABCA1 as a mediator of lipid transport by using a methodology developed in the laboratory to isolate a protein and study its interactions with other compounds. ABCA1 was tagged with the 1D4 peptide at the C terminus and expressed in human HEK 293 cells. Preliminary experiments showed that the tag modified neither the protein expression/localization within the cells nor the ability of ABCA1 to promote cholesterol cellular efflux to apolipoprotein A-I. ABCA1-1D4 was then purified and reconstituted in liposomes. ABCA1 displayed an ATPase activity in phospholipid liposomes that was significantly decreased by cholesterol. Finally, interactions with either cholesterol or apolipoprotein A-I were assessed by binding experiments with protein immobilized on an immunoaffinity matrix. Solid-phase binding assays showed no direct binding of cholesterol or apolipoprotein A-I to ABCA1. Overall, our data support the hypothesis that ABCA1 is able to mediate the transport of cholesterol from cells without direct interaction and that apo A-I primarily binds to membrane surface or accessory protein(s).

  6. A Comparison of Cholesterol Uptake and Storage in Inflammatory and Noninflammatory Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Breonna J. Martin

    2012-01-01

    Full Text Available Although there are many subtypes of breast cancer, inflammatory breast cancer (IBC is arguably the deadliest. Research over the past decade has demonstrated that IBC is a distinct entity from other forms of breast cancer. Important risk factors that have been associated with the development of aggressive breast cancers, such as IBC, include obesity and diet, which are evident in the United States, where the overconsumption of high-fat foods continues to contribute to obesity in the nation. Here we investigate differences in cholesterol uptake and storage between IBC, non-IBC, and mammary epithelial cell lines. Our results demonstrate that compared with human mammary epithelial cells (HMECs, both IBC and non-IBC cells have increased cholesterol content. IBC cells retain intracellular cholesterol esters, free cholesterol, and triglycerides in lipid-deficient environments. In contrast, we observe in cell-type-of-origin-matched non-IBC a significant decrease in lipid content under the same lipid-deficient conditions. These data suggest that cholesterol storage may be affected by the cholesterol content of the environment where the tumor cell was isolated. Here, we suggest that breast cancer cells may migrate when they are unable to obtain cholesterol from their extracellular environments.

  7. Lactoferrin interacts with bile acids and increases fecal cholesterol excretion in rats.

    Science.gov (United States)

    Nakamura, Kanae; Morishita, Satoru; Ono, Tomoji; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Ikeda, Ikuo; Nishino, Hoyoku

    2017-02-01

    Lactoferrin (LF) is a multifunctional cationic protein (pI 8.2-8.9) in mammalian milk. We previously reported that enteric-LF prevented hypercholesterolemia and atherosclerosis in a diet-induced atherosclerosis model using Microminipig, although the underlying mechanisms remain unclear. Because LF is assumed to electrostatically interact with bile acids to inhibit intestinal cholesterol absorption, LF could promote cholesterol excretion. In this study, we assessed the interaction between LF and taurocholate in vitro, and the effect of LF on cholesterol excretion in rats. The binding rate of taurocholate to LF was significantly higher than that to transferrin (pI 5.2-6.3). When rats were administered a high-cholesterol diet (HCD) containing 5% LF, LF was detected using ELISA in the upper small intestine from 7.5 to 60 min after the administration. Rats were fed one of the following diets: control, HCD, or HCD + 5% LF for 21 days. Fecal neutral steroids and hepatic cholesterol levels in the HCD group were significantly higher than those in the control group. The addition of LF to a HCD significantly increased fecal neutral steroids levels (22% increase, p cholesterol levels (17% decrease, p cholesterol excretion via interactions with bile acids.

  8. Red and white wines inhibit cholesterol oxidation induced by free radicals.

    Science.gov (United States)

    Tian, Ling; Wang, Hua; Abdallah, Ahmed Moursy; Prinyawiwatkul, Witoon; Xu, Zhimin

    2011-06-22

    The capabilities of two red (RW) and two white wines (WW) in inhibiting cholesterol oxidation were evaluated using a cholesterol emulsion (CE) system. Each RW or WW was mixed with CE at different (v/v) ratios. Cholesterol oxidation was accelerated by a free radical generator, 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), at 37 °C. The major oxidation product, 7-ketocholesterol, was monitored to determine cholesterol stability in the CE system. At a ratio of 1:250 (RW/CE), 7-ketocholesterol production was not detected during 72 h of oxidation. At a 1:1000 ratio, the inhibition rate of each RW was maintained at 100% at 24 h but decreased afterward. Both WWs had 100% inhibition rate within 48 h at a ratio of 1:10. Also, the capabilities of catechin and resveratrol solutions (1 mg/mL) in inhibiting cholesterol oxidation were studied. Each of the wine polyphenolics showed a 100% of 7-ketocholesterol inhibition rate in 24 h at a ratio of 1:500 (solution/CE). However, the inhibition rate of resveratrol was lower than that of catechin at 48 or 72 h. The results demonstrated that red wine possesses great anti-cholesterol-oxidation capability, which may contribute to health benefits in preventing cardiovascular diseases. Catechin may play a more important role than resveratrol in inhibiting cholesterol oxidation.

  9. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    Science.gov (United States)

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

  10. 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

  11. 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

  12. Brain cholesterol in normal and pathological aging

    Directory of Open Access Journals (Sweden)

    Vanmierlo Tim

    2011-07-01

    Full Text Available Aberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration, which are affected in Alzheimer’s Disease (AD. Cholesterol homeostasis within the brain is independent of that in the rest of the body and needs to be strictly regulated for optimal brain functioning. In contrast with what was initially assumed brain cholesterol homeostasis can be modulated by extra-cerebral factors. We have found that enhancement of the cholesterol-turnover in the brain by administration of the synthetic activator of liver x receptos (LXRs, T0901317, leads to restoration of memory functions in an AD mouse-model.Memory in C57Bl6NCrl mice was not further improved by the same treatment. Moreover, it was found that in contrast with cholesterol, the structurally very similar dietary derived plant sterols can enter the brain. Plant sterols may be natural activators of LXRs. Evidence is provided suggesting that brassicasterol may be a novel additional biomarker in cerebrospinal fluid of AD patients. Insight into the regulation of cerebral cholesterol homeostasis will provide possibilities to modulate the key steps involved and may lead to the development of therapies for the prevention as well as treatment of neurodegenerative diseases such as AD.

  13. 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.

  14. 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.

  15. Tissue storage and control of cholesterol metabolism in man on high cholesterol diets.

    Science.gov (United States)

    Quintão, E C; Brumer, S; Stechhahn, K

    1977-03-01

    The possibility of accumulation of tissue cholesterol in human beings submitted to high cholesterol feeding was investigated in liver biopsies and through fecal sterol balance studies. Feeding to 10 individuals 3.1 to 3.4 g/day of cholesterol for 3 weeks raised the mean serum level from 293 to 349 mg/100 ml, namely 19%, whereas the liver cholesterol content was 417 mg/100 g of wet weight. In 10 control cases eating 0.1--0.4 g/day of cholesterol serum cholesterol remained stable throughout the experimental period and the liver cholesterol content was 256 mg/100 g. Difference of liver colesterol level between the two groups was 62%. In 7 patients submitted to two periods of balance investigation on a cholesterol-free synthetic formula diet respectively prior to (PI) and after (PIII) eating the high cholesterol solid food from 4 to 15 weeks (PII), fecal steroid excretion in PIII exceeded PI in 3 patients. Such data are a direct evidence for the existence of an efficient system to release acutely stored cholesterol. In one patient bile acid excretion accounted for the difference between PIII and PI.

  16. Acyl-coenzyme A:cholesterol acyltransferases

    OpenAIRE

    Chang, Ta-Yuan; Li, Bo-Liang; Chang, Catherine C.Y.; Urano, Yasuomi

    2009-01-01

    The enzymes acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs) are membrane-bound proteins that utilize long-chain fatty acyl-CoA and cholesterol as substrates to form cholesteryl esters. In mammals, two isoenzymes, ACAT1 and ACAT2, encoded by two different genes, exist. ACATs play important roles in cellular cholesterol homeostasis in various tissues. This chapter summarizes the current knowledge on ACAT-related research in two areas: 1) ACAT genes and proteins and 2) ACAT enzymes as...

  17. Peripheral cholesterol, metabolic disorders and Alzheimer's disease.

    Science.gov (United States)

    Ledesma, Maria Dolores; Dotti, Carlos Gerardo

    2012-01-01

    Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

  18. Influence of Water Quality on Cholesterol-Induced Tau Pathology: Preliminary Data

    Directory of Open Access Journals (Sweden)

    D. Larry Sparks

    2011-01-01

    Full Text Available The studies employed the cholesterol-fed rabbit model of Alzheimer's disease (AD to investigate the relationship between AD-like neurofibrillary tangle (NFT neuropathology and tau protein levels as the main component of NFT. We measured brain and plasma tau levels and semiquantified NFT-like neuropathology in cholesterol-fed rabbits administered drinking water of varying quality (distilled, tap, and distilled+copper compared to animals receiving normal chow and local tap water. Total tau levels in plasma were increased in all cholesterol-fed rabbits compared to animals on normal chow, regardless of quality of water. In contrast, increased tau in brain and increased AT8 immunoreactive NFT-like lesions were greatest in cholesterol-fed rabbits administered distilled water. A substantial decrease in brain tau and incidence and density of AT8 immunoreactive NFT-like lesions occurred in cholesterol-fed rabbits administered copper water, and an even greater decrease was observed in cholesterol-fed animals on local tap water. These studies suggest the possibility that circulating tau could be the source of the tau accumulating in the brain.

  19. MILD CHOLESTEROL DEPLETION REDUCES AMYLOID-β PRODUCTION BY IMPAIRING APP TRAFFICKING TO THE CELL SURFACE

    Science.gov (United States)

    Guardia-Laguarta, Cristina; Coma, Mireia; Pera, Marta; Clarimón, Jordi; Sereno, Lidia; Agulló, José M.; Molina-Porcel, Laura; Gallardo, Eduard; Deng, Amy; Berezovska, Oksana; Hyman, Bradley T.; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

    2009-01-01

    It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP-PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. PMID:19457132

  20. Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

    Science.gov (United States)

    Guo, Wenxin; Shu, Yang; Yang, Xiaoping

    2016-06-01

    Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease.

  1. 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.

  2. Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario.

    Science.gov (United States)

    Choi, Sy-Bing; Lew, Lee-Ching; Yeo, Siok-Koon; Nair Parvathy, Seema; Liong, Min-Tze

    2015-01-01

    Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their cholesterol lowering potentials in prevention of hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their conjugated counterparts, thus are less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels. However, some controversies have risen attributed to the activities of deconjugated bile acids that repress the synthesis of bile acids from cholesterol. Deconjugated bile acids have higher binding affinity towards some orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH), which is responsible in bile acid synthesis from cholesterol. This notion was further corroborated by our current docking data, which indicated that deconjugated bile acids have higher propensities to bind with the FXR receptor as compared to conjugated bile acids. Bile acids-activated FXR also induces transcription of the IBABP gene, leading to enhanced recycling of bile acids from the intestine back to the liver, which subsequently reduces the need for new bile formation from cholesterol. Possible detrimental effects due to increased deconjugation of bile salts such as malabsorption of lipids, colon carcinogenesis, gallstones formation and altered gut microbial populations, which contribute to other varying gut diseases, were also included in this review. Our current findings and review substantiate the need to look beyond BSH deconjugation as a single factor/mechanism in strain selection for

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

    Science.gov (United States)

    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.

  4. Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mayra Domínguez-Pérez

    2016-01-01

    Full Text Available Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system.

  5. Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress

    Science.gov (United States)

    Domínguez-Pérez, Mayra; Nuño-Lámbarri, Natalia; Clavijo-Cornejo, Denise; Luna-López, Armando; Souza, Verónica; Bucio, Leticia; Miranda, Roxana U.; Muñoz, Linda; Gomez-Quiroz, Luis Enrique; Uribe-Carvajal, Salvador; Gutiérrez-Ruiz, María Concepción

    2016-01-01

    Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system. PMID:27143995

  6. Raphanus sativus L. var niger as a source of phytochemicals for the prevention of cholesterol gallstones.

    Science.gov (United States)

    Castro-Torres, Ibrahim Guillermo; De la O-Arciniega, Minarda; Gallegos-Estudillo, Janeth; Naranjo-Rodríguez, Elia Brosla; Domínguez-Ortíz, Miguel Ángel

    2014-02-01

    Raphanus sativus L. var niger (black radish) is a plant of the cruciferous family with important ethnobotanical uses for the treatment of gallstones in Mexican traditional medicine. It has been established that the juice of black radish decreases cholesterol levels in plasma and dissolves gallstones in mice. Glucosinolates, the main secondary metabolites of black radish, can hydrolyze into its respective isothiocyanates and have already demonstrated antioxidant properties as well as their ability to diminish hepatic cholesterol levels; such therapeutic effects can prevent the formation of cholesterol gallstones. This disease is considered a current problem of public health. In the present review, we analyze and discuss the therapeutic effects of the main glucosinolates of black radish, as well as the effects that this plant has on cholesterol gallstones disease.

  7. The biological response of cells to nanosecond pulsed electric fields is dependent on plasma membrane cholesterol.

    Science.gov (United States)

    Cantu, Jody C; Tarango, Melissa; Beier, Hope T; Ibey, Bennett L

    2016-11-01

    Previous work from our laboratory demonstrated nanopore formation in cell membranes following exposure to nanosecond pulsed electric fields (nsPEF). We observed differences in sensitivity to nsPEF in both acute membrane injury and 24h lethality across multiple cells lines. Based on these data, we hypothesize that the biological response of cells to nsPEF is dependent on the physical properties of the plasma membrane (PM), including regional cholesterol content. Results presented in this paper show that depletion of membrane cholesterol disrupts the PM and increases the permeability of cells to small molecules, including propidium iodide and calcium occurring after fewer nsPEF. Additionally, cholesterol depletion concurrently decreases the "dose" of nsPEF required to induce lethality. In summary, the results of the current study suggest that the PM cholesterol composition is an important determinant in the cellular response to nsPEF. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Beneficial effect of low dose Amlodipine vs Nifedipine on serum cholesterol profile of rabbits receiving standard diet.

    Directory of Open Access Journals (Sweden)

    Bavane DS, Rajesh CS, Gurudatta Moharir, Bharatha Ambadasu

    2013-01-01

    Full Text Available To investigate the effect of low dose amlodipine v/s nifedipine on serum cholesterol profile of rabbits receiving standard diet. Methods: Fourty Newzealand rabbits were selected for the study. Their cholesterol profile was estimated at the beginning of the study. Rabbits were grouped into 4 groups receiving standard diet (control group, standard diet + vehicle propylene glycol, standard diet + nifedipine dissolved in propylene glycol and standard diet + amlodipine dissolved in propylene glycol. Along with standard diet they were treated with respective drugs for ten weeks. At the end of ten weeks serum cholesterol profile was estimated. Results: The cholesterol profile was estimated at the beginning and at the end of ten weeks. Total cholesterol in the amlodipine group decreased from 97±4.06 mg/dl to 90±4.2 mg/dl and HDL-Cholesterol increased from 32.01±4.40 mg/dl to 37±4.60 mg/dl after 10 week treatment but these changes were not significant. LDL cholesterol decreased significantly in rabbits with low dose of amlodipine from 55.42±3.32 mg/dl to 32.40±3.22 mg/dl and. In the nifedipine group there was a slight increase in total cholesterol from 102.49±5.16 mg/dl to 106±5.39 mg/dl, HDL cholesterol from 34.10±2.80 to 35.16±2.82 mg/dl and LDL cholesterol also increased from 56.20±2.20 mg/dl to 59.00±2.20 mg/dl after 10 week treatment. Conclusion: The study shows amlodipine produces favorable alterations in serum cholesterol profile

  9. Hypolipidemic effect in cholesterol-fed rats of a soluble fiber-rich product obtained from cocoa husks.

    Science.gov (United States)

    Ramos, Sonia; Moulay, Leila; Granado-Serrano, Ana Belén; Vilanova, Olga; Muguerza, Begoña; Goya, Luis; Bravo, Laura

    2008-08-27

    A new soluble cocoa fiber product (SCFP), obtained after enzymatic treatment of cocoa husks, was characterized and its potential health effects studied in an animal model of dietary-induced hypercholesterolemia. The SCFP was rich in soluble dietary fiber (DF) and antioxidant polyphenols. Consumption of a cholesterol-rich diet containing the SCFP as a source of DF resulted in lower food intake and body weight gain in comparison with control groups consuming cholesterol-free or cholesterol-rich diets with cellulose as DF. The cholesterol-rich diet caused remarkable hypercholesterolemia. However, the SCFP diminished the negative impact of the cholesterol-rich diet, buffering the decrease of high density lipoprotein-cholesterol, and the increase of total and low density lipoprotein-cholesterol levels, and lipid peroxidation (malondialdehyde levels) induced by the fatty diet. The SCFP also decreased triglyceride levels to values lower than those in the group fed the cholesterol-free diet. These results put forward the potential application of the SCFP as a dietary supplement or functional food ingredient.

  10. The change in cholesterol content of long chain fatty acid egg during processing and its influence to the Rattus norvegicus L. blood cholesterol content

    Directory of Open Access Journals (Sweden)

    Dini Hardini

    2006-12-01

    Full Text Available Egg containing long chain unsaturated fatty acids is a functional food, because it is highly nutritious and could prevent diseases, (omega 3 and 6 such as coronary heart attack. The research was aimed to measure the change of egg cholesterol content during proceesing: frying, oiless frying and boiling and their influence to the blood plasma cholesterol of normal and hypercholesterolemia rat. Seven treatments of egg yolk were frying at 170°C for 3 min (welldone = GM, and 1min (half medium fried = GSM using deep fryer , oilless frying at 70°C for10 min (fried = TM, and 6 min (half fried = TSM using Teflon pan, and boiling at 100°C for 10’ (boiled = RM dan 4 min (half boiled = RSM using pan provided with thermoregulator and a fresh omega egg as a control. The Completely randomized design was apllied for 4 weeks research period. The data from different treatments were analyzed by Orthogonal Contrast. Fifty 2 months old male rats Rattus norvegicus L. separated in 2 groups; normal and hypercholesterolemia (blood cholesterol > 200 mg dl-1. The rats were placed in individual cage, fed 15 g h-1 day-1 and water drinking ad libitum. The ration was composed of 90% basal commercial feed BR II and 10% egg yolk was given to each animal at 20% of live weight. Factorial 2 x 7 of completely randomized design was applied. The data were analyzed by ANOVA and Duncan’s Multiple Range Test. Processsing method of egg affected to cholesterol content of egg, The lowest and the highest cholesterol contents were observed in TSM (0.30 g/100g and GM (0.37 g/100g, respectively. Biological test using Rattus norvegicus L rat showed that either fresh and processed long chain fatty acid egg decreased plasma cholesterol. The highest and the lowest decreases of cholesterol content were found in the group consumed RSM (8.64% and GM (1.77% for normal rat; and control (46.3% followed by RSM (44.53% and GM (24.86%, respectively. To maintain normal cholesterol and decrease

  11. Healthy Dietary Fats Help Beat High Cholesterol

    Science.gov (United States)

    ... Harvard T.H. Chan School of Public Health. "Saturated fat increases LDL -- bad cholesterol -- which is a major cause of artery-clogging plaque and cardiovascular disease," he said. In clinical trials, reducing use ...

  12. How Is High Blood Cholesterol Treated?

    Science.gov (United States)

    ... fat is found in some meats, dairy products, chocolate, baked goods, and deep-fried and processed foods. ... and raise your HDL cholesterol level. People gain health benefits from as little as 60 minutes of moderate- ...

  13. estimations of cholesterol, triglycerides and fractionation

    African Journals Online (AJOL)

    Preferred Customer

    2Department of Science Laboratory Technology, Moshood Abiola ... (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) in 53 female .... In this report, concentrations of the following biochemical parameters in the serum were.

  14. [Cholesterol and atherosclerosis. Historical considerations and treatment].

    Science.gov (United States)

    Zárate, Arturo; Manuel-Apolinar, Leticia; Basurto, Lourdes; De la Chesnaye, Elsa; Saldívar, Iván

    2016-01-01

    Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol»; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

  15. Poly(ethylene glycol-cholesterol inhibits L-type Ca2+ channel currents and augments voltage-dependent inactivation in A7r5 cells.

    Directory of Open Access Journals (Sweden)

    Rikuo Ochi

    Full Text Available Cholesterol distributes at a high density in the membrane lipid raft and modulates ion channel currents. Poly(ethylene glycol cholesteryl ether (PEG-cholesterol is a nonionic amphipathic lipid consisting of lipophilic cholesterol and covalently bound hydrophilic PEG. PEG-cholesterol is used to formulate lipoplexes to transfect cultured cells, and liposomes for encapsulated drug delivery. PEG-cholesterol is dissolved in the external leaflet of the lipid bilayer, and expands it to flatten the caveolae and widen the gap between the two leaflets. We studied the effect of PEG-cholesterol on whole cell L-type Ca(2+ channel currents (I(Ca,L recorded from cultured A7r5 arterial smooth muscle cells. The pretreatment of cells with PEG-cholesterol decreased the density of ICa,L and augmented the voltage-dependent inactivation with acceleration of time course of inactivation and negative shift of steady-state inactivation curve. Methyl-β-cyclodextrin (MβCD is a cholesterol-binding oligosaccharide. The enrichment of cholesterol by the MβCD:cholesterol complex (cholesterol (MβCD caused inhibition of I(Ca,L but did not augment voltage-dependent inactivation. Incubation with MβCD increased I(Ca,L, slowed the time course of inactivation and shifted the inactivation curve to a positive direction. Additional pretreatment by a high concentration of MβCD of the cells initially pretreated with PEG-cholesterol, increased I(Ca,L to a greater level than the control, and removed the augmented voltage-dependent inactivation. Due to the enhancement of the voltage-dependent inactivation, PEG-cholesterol inhibited window I(Ca,L more strongly as compared with cholesterol (MβCD. Poly(ethylene glycol conferred to cholesterol the efficacy to induce sustained augmentation of voltage-dependent inactivation of I(Ca,L.

  16. Assessing possible hazards of reducing serum cholesterol.

    OpenAIRE

    Law, M. R.; Thompson, S. G.; Wald, N J

    1994-01-01

    OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration....

  17. Cholesterol treatment practices of primary care physicians.

    OpenAIRE

    Hyman, D J; Maibach, E W; Flora, J A; Fortmann, S.P.

    1992-01-01

    The active involvement of primary care physicians is necessary in the diagnosis and treatment of elevated blood cholesterol. Empirical evidence suggests that primary care physicians generally initiate dietary and pharmacological treatment at threshold values higher than is currently recommended. To determine current treatment thresholds and establish factors that distinguish physicians who are more likely to initiate therapy at lower cholesterol values, 119 primary care physicians in four nor...

  18. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    Institute of Scientific and Technical Information of China (English)

    Carlos; LJ; Vrins

    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 the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In t...

  19. 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.

  20. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  1. 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.

  2. Obesity, cholesterol metabolism, and breast cancer pathogenesis.

    Science.gov (United States)

    McDonnell, Donald P; Park, Sunghee; Goulet, Matthew T; Jasper, Jeff; Wardell, Suzanne E; Chang, Ching-Yi; Norris, John D; Guyton, John R; Nelson, Erik R

    2014-09-15

    Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition, significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor in macrophages and possibly other cells, is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. Cancer Res; 74(18); 4976-82. ©2014 AACR. ©2014 American Association for Cancer Research.

  3. Obesity, Cholesterol Metabolism and Breast Cancer Pathogenesis

    Science.gov (United States)

    McDonnell, Donald P.; Park, Sunghee; Goulet, Matthew T.; Jasper, Jeff; Wardell, Suzanne E.; Chang, Ching-yi; Norris, John D.; Guyton, John R.; Nelson, Erik R.

    2014-01-01

    Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor (LXR) in macrophages and possibly other cells is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor (ER) agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. PMID:25060521

  4. Cholesterol modulates the dimer interface of the β₂-adrenergic receptor via cholesterol occupancy sites.

    Science.gov (United States)

    Prasanna, Xavier; Chattopadhyay, Amitabha; Sengupta, Durba

    2014-03-18

    The β2-adrenergic receptor is an important member of the G-protein-coupled receptor (GPCR) superfamily, whose stability and function are modulated by membrane cholesterol. The recent high-resolution crystal structure of the β2-adrenergic receptor revealed the presence of possible cholesterol-binding sites in the receptor. However, the functional relevance of cholesterol binding to the receptor remains unexplored. We used MARTINI coarse-grained molecular-dynamics simulations to explore dimerization of the β2-adrenergic receptor in lipid bilayers containing cholesterol. A novel (to our knowledge) aspect of our results is that receptor dimerization is modulated by membrane cholesterol. We show that cholesterol binds to transmembrane helix IV, and cholesterol occupancy at this site restricts its involvement at the dimer interface. With increasing cholesterol concentration, an increased presence of transmembrane helices I and II, but a reduced presence of transmembrane helix IV, is observed at the dimer interface. To our knowledge, this study is one of the first to explore the correlation between cholesterol occupancy and GPCR organization. Our results indicate that dimer plasticity is relevant not just as an organizational principle but also as a subtle regulatory principle for GPCR function. We believe these results constitute an important step toward designing better drugs for GPCR dimer targets.

  5. Cost-effective and highly sensitive cholesterol microsensors with fast response based on the enzyme-induced conductivity change of polyaniline

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Kuan-Chung; Chu, Chia-Ho; Hsu, Chen-Pin; Kang, Yen-Wen; Fang, Jung-Ying; Chen, Chih-Chen; Li, Sheng-Shian; Andrew Yeh, J.; Yao, Da-Jeng; Wang, Yu-Lin, E-mail: ylwang@mx.nthu.edu.tw [Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu 300, Taiwan (China); Hsu, Chia-Hsien [Division of Medical Engineering, National Health Research Institutes, MiaoLi, Taiwan (China); Huang, Yu-Fen [Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu 300, Taiwan (China)

    2014-09-15

    In this study, a cost-effective and highly sensitive cholesterol microsensor, which is consisted of cholesterol oxidase (ChOx), horseradish peroxidase (HRP), and polyaniline (PANI), was developed based on the enzyme-induced conductivity change of PANI with fast response. Hydrogen peroxide is produced via the reaction between cholesterol and ChOx, which was immobilized in a dialysis membrane. The produced hydrogen peroxide can oxidize HRP, which can be reduced by oxidizing PANI, thus resulting in decreased conductivity of the polyaniline thin film. The reduced HRP can be oxidized again by hydrogen peroxide and the cycle of the oxidation/reduction continues until all hydrogen peroxide are reacted, leading to the high sensitivity of the sensor due to the signal contributed from all hydrogen peroxide molecules. Cholesterol was detected near the physiological concentrations ranging from 100 mg/dl to 400 mg/dl with the cholesterol microsensors. The results show linear relation between cholesterol concentration and the conductivity change of the PANI. The microsensor showed no response to cholesterol when the PANI was standalone without cholesterol oxidase immobilized, indicating that the enzymatic reaction is required for cholesterol detection. The simple process of the sensor fabrication allows the sensor to be cost-effective and disposable usage. This electronic cholesterol microsensor is promising for point-of-care health monitoring in cholesterol level with low cost and fast response.

  6. Niacin and cholesterol: role in cardiovascular disease (review).

    Science.gov (United States)

    Ganji, Shobha H; Kamanna, Vaijinath S; Kashyap, Moti L

    2003-06-01

    Niacin has been widely used as a pharmacologic agent to regulate abnormalities in plasma lipid and lipoprotein metabolism and in the treatment of atherosclerotic cardiovascular disease. Although the use of niacin in the treatment of dyslipidemia has been reported as early as 1955, only recent studies have yielded an understanding about the cellular and molecular mechanism of action of niacin on lipid and lipoprotein metabolism. In brief, the beneficial effect of niacin to reduce triglycerides and apolipoprotein-B containing lipoproteins (e.g., VLDL and LDL) are mainly through: a) decreasing fatty acid mobilization from adipose tissue triglyceride stores, and b) inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles. The mechanism of action of niacin to raise HDL is by decreasing the fractional catabolic rate of HDL-apo AI without affecting the synthetic rates. Additionally, niacin selectively increases the plasma levels of Lp-AI (HDL subfraction without apo AII), a cardioprotective subfraction of HDL in patients with low HDL. Using human hepatocytes (Hep G2 cells) as an in vitro model system, recent studies indicate that niacin selectively inhibits the uptake/removal of HDL-apo AI (but not HDL-cholesterol ester) by hepatocytes, thereby increasing the capacity of retained HDL-apo AI to augment cholesterol efflux through reverse cholesterol transport pathway. The studies discussed in this review provide evidence to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin.

  7. The Structural Basis of Cholesterol Activity in Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brett N.; Bielska, Agata; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.

    2013-10-15

    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

  8. Adrenal steroidogenesis disruption caused by HDL/cholesterol suppression in diethylstilbestrol-treated adult male rat.

    Science.gov (United States)

    Haeno, Satoko; Maeda, Naoyuki; Yamaguchi, Kousuke; Sato, Michiko; Uto, Aika; Yokota, Hiroshi

    2016-04-01

    The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver.

  9. A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

    Directory of Open Access Journals (Sweden)

    Takahiro Furune

    2014-12-01

    Full Text Available Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, α-cyclodextrin (α-CD is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that α-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of α-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of α-CD on micellar solubility of cholesterol.Results: α-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF, and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and α-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and α-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of α-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated.Conclusion: This study suggests that α-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with α-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by α-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with α-CD addition.

  10. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  11. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes

    Science.gov (United States)

    Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Landrock, Kerstin K.; Martin, Gregory G.; Landrock, Danilo; Payne, H. Ross; Atshaves, Barbara P.; Kier, Ann B.

    2012-01-01

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  12. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  13. Evaluation of Sample Handling Effects on Serum Vitamin E and Cholesterol Concentrations in Alpacas

    Directory of Open Access Journals (Sweden)

    Andrea S. Lear

    2014-01-01

    Full Text Available Clinical cases of vitamin E deficiencies have been diagnosed in camelids and may indicate that these species are more sensitive to inadequate vitamin E in hay-based diets compared to other ruminant and equine species. In bovine, cholesterol has been reported to affect vitamin E concentrations. In order to evaluate vitamin E deficiencies in camelids, the effects of collection and storage of the blood samples prior to processing were necessary. Reports vary as to factors affecting vitamin E and cholesterol in blood samples, and diagnostic laboratories vary in instructions regarding sample handling. Blood was collected from healthy alpacas and processed under conditions including exposure to fluorescent light, serum and red blood cell contact, tube stopper contact, temperature, and hemolysis. Serum vitamin E and cholesterol concentrations were then measured. Statistical analyses found that the vitamin E concentrations decreased with prolonged contact with the tube stopper and with increasing hemolysis. Vitamin E concentration variations were seen with other factors but were not significant. Time prior to serum separation and individual animal variation was found to alter cholesterol concentrations within the sample, yet this finding was clinically unremarkable. No correlation was seen between vitamin E and cholesterol concentration, possibly due to lack of variation of cholesterol.

  14. Cardiovascular protection of deep-seawater drinking water in high-fat/cholesterol fed hamsters.

    Science.gov (United States)

    Hsu, Chin-Lin; Chang, Yuan-Yen; Chiu, Chih-Hsien; Yang, Kuo-Tai; Wang, Yu; Fu, Shih-Guei; Chen, Yi-Chen

    2011-08-01

    Cardiovascular protection of deep-seawater (DSW) drinking water was assessed using high-fat/cholesterol-fed hamsters in this study. All hamsters were fed a high-fat/cholesterol diet (12% fat/0.2% cholesterol), and drinking solutions were normal distiled water (NDW, hardness: 2.48ppm), DSW300 (hardness: 324.5ppm), DSW900 (hardness: 858.5ppm), and DSW1500 (hardness: 1569.0ppm), respectively. After a 6-week feeding period, body weight, heart rates, and blood pressures of hamsters were not influenced by DSW drinking waters. Serum total cholesterol (TC), triacylglycerol (TAG), atherogenic index, and malondialdehyde (MDA) levels were decreased (pdrinking-water groups, as compared to those in the NDW group. Additionally, increased (pdrinking-water groups. Hepatic low-density-lipoprotein receptor (LDL receptor) and cholesterol-7α-hydroxylase (CYP7A1) gene expressions were upregulated (pdrinking waters. These results demonstrate that DSW drinking water benefits the attenuation of high-fat/cholesterol-diet-induced cardiovascular disorders in hamsters.

  15. Has the prevalence of cholesterol gallstones increased in Korea? A preliminary single-center experience.

    Science.gov (United States)

    Kim, Ju Wan; Oh, Hyoung-Chul; Do, Jae Hyuk; Choi, Yoo-Shin; Lee, Seung Eun

    2013-10-01

    We aimed to determine the prevalence of cholesterol gallstones, the compositional changes of gallstones and its predisposing factors in Korea with this single-center study. Data of 365 patients who underwent cholecystectomy for cholecystolithiasis from July 2008 to September 2011 were reviewed. Based on the compositional analysis of the gallstones, patients were assigned to either cholesterol gallstone group or pigment gallstone group. The characteristics of the patients and the gallstones were summarized and compared. After eight patients with mixed gallstones were excluded, 357 patients were enrolled in the study, including cholesterol gallstones in 175 (49.0%) and pigment gallstones in 182 (51.0%). The number of patients with cholecystolithiasis increased but the prevalence of cholesterol gallstone decreased with age. Compared with the pigment gallstone group, the cholesterol gallstone group was associated with young age (gallstones in Korea has been stationary so far, but may change in the future since cholesterol gallstones are increasingly prevalent in the young generation. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  16. The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance

    Directory of Open Access Journals (Sweden)

    Manya Warrier

    2015-01-01

    Full Text Available Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO have recently been linked to cardiovascular disease (CVD risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3 as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.

  17. Selective cholesterol adsorption by molecular imprinted polymeric nanospheres and application to GIMS.

    Science.gov (United States)

    Inanan, Tülden; Tüzmen, Nalan; Akgöl, Sinan; Denizli, Adil

    2016-11-01

    Molecular imprinted polymers (MIPs) are tailor-made materials with selective recognition to the target. The goals of this study were to prepare cholesterol imprinted polymeric nanospheres (CIPNs) and optimize their adsorption parameters and also to use CIPNs for adsorption of cholesterol (CHO), which is an important physiological biomacromolecule, from gastrointestinal mimicking solution (GIMS). Pre-polymerization complex was prepared using CHO as template and N-methacryloylamido-(l)-phenylalanine methyl ester (MAPA). This complex was polymerized with 2-hydroxyethyl methacrylate (HEMA). CHO was removed by MeOH and tetrahydrofuran (THF). Adsorption studies were performed after chacterization studies to interrogate the effects of time, initial concentration, temperature, and ionic strength on CHO adsorption onto CIPNs. Maximum adsorption capacity (714.17mg/g) was higher than that of cholesterol imprinted polymers in literature. Pseudo-second-order kinetics and Langmuir isotherm fitted best with the adsorption onto CIPNs. 86% of adsorbed cholesterol was desorbed with MeOH:HAc (80:20, v/v) and CIPNs were used in adsorption-desorption cycle for 5-times with a decrease as 12.28%. CHO analogues; estron, estradiol, testosterone, and progesterone were used for competitive adsorption. The relative selectivity coefficients of CINPs for cholesterol/estron and cholesterol/testosterone were 3.84 and 10.47 times greater than the one of non-imprinted polymeric nanospheres (NIPNs) in methanol, respectively.

  18. PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus.

    Science.gov (United States)

    Xu, Daqian; Wang, Zheng; Zhang, Yuxue; Jiang, Wei; Pan, Yi; Song, Bao-Liang; Chen, Yan

    2015-08-27

    Cholesterol biosynthesis is regulated by transcription factors SREBPs and their escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is unknown. Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the Golgi. PAQR3 promotes Scap/SREBP complex formation, potentiates SREBP processing and enhances lipid synthesis. The mutually exclusive interaction between Scap and PAQR3 or Insig-1 is regulated by cholesterol level. PAQR3 knockdown in liver blunts SREBP pathway and decreases hepatic cholesterol content. Disrupting the interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP processing and activation. Thus, PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis.

  19. Effects of cholesterol depletion on membrane nanostructure in MCF-7 cells by atomic force microscopy

    Science.gov (United States)

    Wang, Yuhua; Jiang, Ningcheng; Shi, Aisi; Zheng, Liqin; Yang, Hongqin; Xie, Shusen

    2017-02-01

    The cell membrane is composed of phospholipids, glycolipids, cholesterol and proteins that are dynamic and heterogeneous distributed in the bilayer structure and many researches have showed that the plasma membrane in eukaryotic cells contains microdomains termed "lipid raft" in which cholesterol, sphingolipids and specific membrane proteins are enriched. Cholesterol extraction induced lipid raft disruption is one of the most widely used methods for lipid raft research and MβCD is a type of solvent to extract the cholesterol from cell membranes. In this study, the effect of MβCD treatment on the membrane nanostructure in MCF-7 living cells was investigated by atomic force microscopy. Different concentrations of MβCD were selected to deplete cholesterol for 30 min and the viability of cells was tested by MTT assay to obtain the optimal concentration. Then the nanostructure of the cell membrane was detected. The results show that an appropriate concentration of MβCD can induce the alteration of cell membranes nanostructure and the roughness of membrane surface decreases significantly. This may indicate that microdomains of the cell membrane disappear and the cell membrane appears more smoothly. Cholesterol can affect nanostructure and inhomogeneity of the plasma membrane in living cells.

  20. Single particle tracking with sterol modulation reveals the cholesterol-mediated diffusion properties of integrin receptors

    Science.gov (United States)

    Arora, Neha; Syed, Aleem; Sander, Suzanne; Smith, Emily A.

    2014-12-01

    A combination of sterol modulation with cyclodextrins plus fluorescence microscopy revealed a biophysical mechanism behind cholesterol’s influence on the diffusion of a ubiquitous class of receptors called integrins. The heterogeneous diffusion of integrins bound to ligand-coated quantum dots was measured using single particle tracking (SPT), and the ensemble changes in integrin diffusion were measured by fluorescence recovery after photobleaching (FRAP). A 25 ± 1% reduction of membrane cholesterol resulted in three significant changes to the diffusion of ligand-bound αPS2CβPS integrins as measured by SPT. There was a 23% increase in ligand-bound mobile integrins; there was a statistically significant increase in the average diffusion coefficient inside zones of confined diffusion, and histograms of confined integrin trajectories showed an increased frequency in the range of 0.1-1 μm2 s-1 and a decreased frequency in the 0.001-0.1 μm2 s-1 range. No statistical change was measured in the duration of confinement nor the size of confined zones. Restoring the cholesterol-depleted cells with exogenous cholesterol or exogenous epicholesterol resulted in similar diffusion properties. Epicholesterol differs from cholesterol in the orientation of a single hydroxyl group. The ability of epicholesterol to substitute for cholesterol suggests a biophysical mechanism for cholesterol’s effect on integrin diffusion. Influences of bilayer thickness, viscosity and organization are discussed as possible explanations for the measured changes in integrin diffusion when the membrane cholesterol concentration is reduced.

  1. Lactobacillus plantarum CUL66 can impact cholesterol homeostasis in Caco-2 enterocytes.

    Science.gov (United States)

    Michael, D R; Moss, J W E; Calvente, D Lama; Garaiova, I; Plummer, S F; Ramji, D P

    2016-06-01

    Hypercholesterolemia drives the development of cardiovascular disease, the leading cause of mortality in western society. Supplementation with probiotics that interfere with cholesterol metabolism may provide a contribution to disease prevention. Lactobacillus plantarum CUL66 (NCIMB 30280) has been assessed in vitro for its ability to impact cholesterol absorption. L. plantarum CUL66 tested positive for bile salt hydrolase activity and the ability to assimilate cholesterol from culture media. RT-qPCR analysis showed that the bacterium significantly decreased the expression of Niemann-Pick C1-like 1 and ATP-binding cassette transporter-1 in polarised Caco-2 cells after 6 h exposure. Conversely, the expression of ATP-binding cassette sub-family G member (ABCG)-5 and ABCG-8, and 3-hydroxy-3-methylglutaryl-CoA reductase were significantly increased. Using a radiolabelled assay, we also observed significant reductions in the uptake and basolateral efflux of cholesterol by Caco-2 cells exposed to L. plantarum CUL66. This in vitro study identified L. plantarum CUL66 as a cholesterol lowering bacteria by highlighting its ability to beneficially regulate multiple in vitro events associated with intestinal cholesterol metabolism and provides evidence of efficacy for its inclusion in future in vivo studies.

  2. 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.

  3. Metabolism of adrenal cholesterol in man

    Science.gov (United States)

    Borkowski, Abraham; Delcroix, Claude; Levin, Sam

    1972-01-01

    The synthesis of adrenal cholesterol, its esterification and the synthesis of the glucocorticosteroid hormones were studied in vitro on human adrenal tissue. It was found that the synthesis of adrenal cholesterol may normally be small in the zona “fasciculata,” particularly when compared with the synthesis of the glucocorticosteroid hormones, that it is several times higher in the zona “reticularis” where esterified cholesterol is less abundant, and that under ACTH stimulation it increases strikingly and proportionally to the degree of esterified adrenal cholesterol depletion. On the other hand, the relative rate of esterification as well as the concentration of free adrenal cholesterol are remarkably stable: they do not differ according to the adrenal zonation and are unaffected by ACTH. Furthermore, from a qualitative point of view, the relative proportions of Δ1 and Δ2 cholesteryl esters formed in situ are similar to those anticipated from their relative concentrations, suggesting that the characteristic fatty acid distribution of the adrenal cholesteryl esters results from an in situ esterification rather than from a selective uptake of the plasma cholesteryl esters. Besides, the in vitro esterification reveals a propensity to the formation of the most unsaturated cholesteryl esters. Regarding hydrocortisone and corticosterone, their synthesis tends to be more elevated in the zona “fasciculata.” Despite its higher cholesterol concentration the zona “fasciculata” should not therefore be viewed as a quiescent functional complement to the zona “reticularis” and the cortical distribution of glucocorticosteroid hormone synthesis is quite distinct from that of adrenal cholesterol synthesis. PMID:4338120

  4. Aspirin Prevention of Cholesterol Gallstone Formation in Prairie Dogs

    Science.gov (United States)

    Lee, Sum P.; Carey, Martin C.; Lamont, J. Thomas

    1981-03-01

    When prairie dogs (Cynomys ludovicianus) are fed a diet containing cholesterol, a marked increase in gallbladder mucin secretion parallels the evolution of cholesterol supersaturated bile. Gelation of mucin precedes the precipitation of cholesterol liquid and solid crystals and the development of gallstones. Aspirin given to prairie dogs inhibited mucin hypersecretion and gel accumulation and prevented gallstone formation without influencing the cholesterol content of supersaturated bile. This suggests that gallbladder mucin is a nucleation matrix for cholesterol gallstones.

  5. Aspirin prevention of cholesterol gallstone formation in prairie dogs.

    Science.gov (United States)

    Lee, S P; Carey, M C; LaMont, J T

    1981-03-27

    When prairie dogs (Cynomys ludovicianus) are fed a diet containing cholesterol, a marked increase in gallbladder mucin secretion parallels the evolution of cholesterol supersaturated bile. Gelation of mucin precedes the precipitation of cholesterol liquid and solid crystals and the development of gallstones. Aspirin given to prairie dogs inhibited mucin hypersecretion and gel accumulation and prevented gallstone formation without influencing the cholesterol content of supersaturated bile. This suggests that gallbladder mucin is a nucleation matrix for cholesterol gallstones.

  6. Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.

    Directory of Open Access Journals (Sweden)

    Xuemei Huang

    Full Text Available BACKGROUND: Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson's disease (PD. This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression. METHODS: Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs and 95% confidence intervals (CI were determined for increasing serum cholesterol concentration (in quintiles for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins. RESULTS: The overall mean cholesterol level was 216 mg/dL (range 100-355. The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95%CI, for each higher quintile (in ascending order are 0.83 (0.59-1.16; 0.86 (0.61-1.20; 0.84 (0.60-1.18; and 0.75 (0.52-1.09. The HR for one standard deviation (SD increase = 0.90 [(0.80-1.01, p for trend = 0.09]. This trend was found in males (HR per SD = 0.88 [(0.77-1.00, p for trend = 0.05], but not in females [HR = 1.03 (0.81-1.32]. CONCLUSIONS: This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.

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

    NARCIS (Netherlands)

    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

    2013-01-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the non-biliary 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

  8. Transintestinal and Biliary Cholesterol Secretion Both Contribute to Macrophage Reverse Cholesterol Transport in Rats

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Dikkers, Arne; Koehorst, Martijn; Havinga, Rick; Kuipers, Folkert; Tietge, Uwe J F; Groen, Albert K

    2017-01-01

    OBJECTIVE: Reverse cholesterol transport comprises efflux of cholesterol from macrophages and its subsequent removal from the body with the feces and thereby protects against formation of atherosclerotic plaques. Because of lack of suitable animal models that allow for evaluation of the respective c

  9. Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

    Science.gov (United States)

    Wang, Helen H; Portincasa, Piero; de Bari, Ornella; Liu, Kristina J; Garruti, Gabriella; Neuschwander-Tetri, Brent A; Wang, David Q.-H

    2013-01-01

    Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors, and represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. The primary pathophysiologic event is persistent hepatic hypersecretion of biliary cholesterol, which has both hepatic and small intestinal components. The majority of the environmental factors are probably related to Western-type dietary habits, including excess cholesterol consumption. Laparoscopic cholecystectomy, one of the most commonly performed surgical procedures in the US, is nowadays a major treatment for gallstones. However, it is invasive and can cause surgical complications, and not all patients with symptomatic gallstones are candidates for surgery. The hydrophilic bile acid, ursodeoxycholic acid (UDCA) has been employed as first-line pharmacological therapy in a subgroup of symptomatic patients with small, radiolucent cholesterol gallstones. Long-term administration of UDCA can promote the dissolution of cholesterol gallstones. However, the optimal use of UDCA is not always achieved in clinical practice because of failure to titrate the dose adequately. Therefore, the development of novel, effective, and noninvasive therapies is crucial for reducing the costs of health care associated with gallstones. In this review, we summarize recent progress in investigating the inhibitory effects of ezetimibe and statins on intestinal absorption and hepatic biosynthesis of cholesterol, respectively, for the treatment of gallstones, as well as in elucidating their molecular mechanisms by which combination therapy could prevent this very common liver disease worldwide. PMID:23419155

  10. Cholesterol content and methods for cholesterol determination in meat and poultry

    Science.gov (United States)

    Available data for cholesterol content of beef, pork, poultry, and processed meat products were reported. Although the cholesterol concentration in meat and poultry can be influenced by various factors, effects of animal species, muscle fiber type, and muscle fat content are focused on in this revi...

  11. A new cholesterol biosynthesis and absorption disorder associated with epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration.

    Science.gov (United States)

    Korematsu, Seigo; Uchiyama, Shin-ichi; Honda, Akira; Izumi, Tatsuro

    2014-06-01

    Cholesterol is one of the main components of human cell membranes and constitutes an essential substance in the central nervous system, endocrine system, and its hormones, including sex hormones. A 19-year-old male patient presented with failure to thrive, psychomotor deterioration, intractable epilepsy, hypogonadism, and cerebro-cerebello-bulbar degeneration. His serum level of cholesterol was low, ranging from 78.7 to 116.5 mg/dL. The serum concentrations of intermediates in the cholesterol biosynthesis pathway, such as 7-dehydrocholesterol, 8-dehydrocholesterol, desmosterol, lathosterol, and dihydrolanosterol, were not increased. In addition, the levels of the urinary cholesterol biosynthesis marker mevalonic acid, the serum cholesterol absorption markers, campesterol and sitosterol, and the serum cholesterol catabolism marker, 7α-hydroxycholesterol, were all low. A serum biomarker analysis indicated that the patient's basic abnormality differed from that of Smith-Lemli-Opitz syndrome and other known disorders of cholesterol metabolism. Therefore, this individual may have a new metabolic disorder with hypocholesterolemia because of decreased biosynthesis and absorption of cholesterol. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice.

    Science.gov (United States)

    Zong, Chuanlong; Yu, Yang; Song, Guohua; Luo, Tian; Li, Luqin; Wang, Xinnong; Qin, Shucun

    2012-02-01

    Chitosan oligosaccharides (COS) are beneficial in improving plasma lipids and diminishing atherosclerotic risks. In this study, we examined the effects of COS on reverse cholesterol transport (RCT) in C57BL/6 mice. (3)H-cholesterol-laden macrophages were injected intraperitoneally into mice fed with various dosage of COS (250, 500, 1000 mg/kg mouse weight, respectively) or vehicle by gastric gavages. Plasma lipid level was determined and (3)H-cholesterol was traced in plasma, liver, bile and feces. The effects of COS on hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) and scavenger receptor BI (SR-BI) expression were also investigated. COS administration led to a significant decrease in plasma total cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in peritoneal macrophage-derived (3)H-cholesterol in liver and bile as well as in feces. Liver protein expressions of CYP7A1, SR-BI and LDL receptor (LDL-R) were improved in a dosage-dependent manner in COS-administered mice. Our findings provide the first in vivo demonstration of a positive role for COS in RCT pathway and hepatic CYP7A1 and SR-BI expression in mice. Additionally, the LDL cholesterol lowering effect might be relative to hepatic LDL-R expression stimulated by COS in mice.

  13. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Maki Kobayashi

    2014-12-01

    Full Text Available A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet, a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet, a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet, or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet for five weeks. The plasma total cholesterol (TC level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein.

  14. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    Science.gov (United States)

    Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

    2014-01-01

    A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein. PMID:25514389

  15. 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

    variation in NPC1L1, mimicking the effect of ezetimibe, was associated with reduced risk of ischaemic vascular disease (IVD) and with increased risk of symptomatic gallstone disease. METHODS AND RESULTS: We included 67 385 individuals from the general population. Of these, 5255 and 3886 individuals...... 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...

  16. 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.

  17. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

  18. Effect of Inhibition of Intestinal Cholesterol Absorption on the Prevention of Cholesterol Gallstone Formation.

    Science.gov (United States)

    Portincasa, Piero; Wang, David Q-H

    2017-01-01

    Cholesterol cholelithiasis is a multifactorial hepatobiliary disease. Interactions between genetic and environmental factors play a critical role in biliary cholesterol homeostasis and its imbalance enhances cholelithogenesis. In patients developing symptoms or complications of gallstone disease, laparoscopic cholecystectomy is recommended for treatment of gallstones. In a subgroup of patients with small, radiolucent pure cholesterol gallstones, the hydrophilic bile acid, ursodeoxycholic acid (UDCA) is still considered the only pharmacological therapy able to induce oral litholysis. Identifying novel and effective pharmacological therapies is being investigated. We propose that the specific intestinal Niemann-Pick C1-like 1 protein inhibitor ezetimibe is a potential agent for preventing gallstone formation by reducing bioavailability of intestine- derived cholesterol to the liver for biliary secretion and desaturating bile through the inhibition of intestinal absorption of cholesterol. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. 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.

  20. 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.

  1. The study of serum Carnitine, Triglyceride and Cholesterol changes in pregnant and non-pregnant women

    Directory of Open Access Journals (Sweden)

    Zahraei M

    1993-04-01

    Full Text Available Carnitine is a water-soluble quaternary amine which increases the long-chain fatty acid metabolism by facilitation of their transport to the oxidation site (mitochondria. Carnitine most likely is present in all animal species, in many microorganisms, and in many plants. In this study, we determined the carnitine level of sera in pregnant and non-pregnant women by segade modified method. Average concentration of carnitine in the sera of fifty pregnant women was about 25/83 umol/I: First trimester-30.96 umol/I. Second trimester-29.11 umol/I. Third trimester-25.11 umol/I. concentration of cholesterol and triglyceride in the above-mentioned group was the following: Cholesterol: 258.84 mg/dl triglyceride: 267.02 mg/dl. The above values show that the carnitine level in sera of pregnant women decreases significantly and this decrease is tolerated well by pregnant women. According to our results, the serum carnitine concentration in pregnant women gradually decreases as gestation proceeds. So that the end of this period, is half of its concentration before conception. During pregnancy, there was an inverse correlation between carnitine level and that of cholesterol and triglycerides. Decrease in carnitine concentration and increase in cholesterol and triglyceride levels may be due to the following factors: 1 Increase in FFA oxidation in pregnancy. 2 Hormones. 3 Dilution of the blood. 4 Decrease in Fe storage in pregnant women.

  2. Cholesterol-Lowering Activity of Tartary Buckwheat Protein.

    Science.gov (United States)

    Zhang, Chengnan; Zhang, Rui; Li, Yuk Man; Liang, Ning; Zhao, Yimin; Zhu, Hanyue; He, Zouyan; Liu, Jianhui; Hao, Wangjun; Jiao, Rui; Ma, Ka Ying; Chen, Zhen-Yu

    2017-03-08

    Previous research has shown that Tartary buckwheat flour is capable of reducing plasma cholesterol. The present study was to examine the effect of rutin and Tartary buckwheat protein on plasma total cholesterol (TC) in hypercholesterolemia hamsters. In the first animal experiment, 40 male hamsters were divided into four groups fed either the control diet or one of the three experimental diets containing 8.2 mmol rutin, 8.2 mmol quercetin, or 2.5 g kg(-1) cholestyramine, respectively. Results showed that only cholestyramine but not rutin and its aglycone quercetin decreased plasma TC, which suggested that rutin was not the active ingredient responsible for plasma TC-lowering activity of Tartary buckwheat flour. In the second animal experiment, 45 male hamsters were divided into five groups fed either the control diet or one of the four experimental diets containing 24% Tartary buckwheat protein, 24% rice protein, 24% wheat protein, or 5 g kg(-1) cholestyramine, respectively. Tartary buckwheat protein reduced plasma TC more effectively than cholestyramine (45% versus 37%), while rice and wheat proteins only reduced plasma TC by 10-13%. Tartary buckwheat protein caused 108% increase in the fecal excretion of total neutral sterols and 263% increase in the fecal excretion of total acidic sterols. real-time polymerase chain reaction and Western blotting analyses showed that Tartary buckwheat protein affected the gene expression of intestinal Niemann-Pick C1-like protein 1 (NPC1L1), acyl CoA:cholesterol acyltransferase 2 (ACAT2), and ATP binding cassette transporters 5 and 8 (ABCG5/8) in a down trend, whereas it increased the gene expression of hepatic cholesterol-7α -hydroxylase (CYP7A1). It was concluded that Tartary buckwheat protein was at least one of the active ingredients in Tartary buckwheat flour to lower plasma TC, mainly mediated by enhancing the excretion of bile acids via up-regulation of hepatic CYP7A1 and also by inhibiting the absorption of dietary

  3. Biosynthesis of membrane cholesterol during peripheral nerve development, degeneration and regeneration.

    Science.gov (United States)

    Yao, J K

    1988-09-01

    Biosynthesis of peripheral nerve cholesterol was investigated by the in vivo and in vitro incorporation of [1-14C]-acetate into sciatic endoneurium of normal rats during development, degeneration and regeneration. Labeled sterols were rapidly formed (less than 10 min) within the endoneurial portion of sciatic nerve after [1-14C]acetate administration by intraneural injection. The majority of labeled sterols were initially found in lanosterol and desmosterol. After six hr, the 14C-labeling in both precursors was decreased to minimum, whereas cholesterol became the major labeled product of sterol. As myelination proceeded, the incorporation of [1-14C]acetate into endoneurial cholesterol decreased rapidly and reached a minimum after six mo. In mature adult nerve, an increased proportion of biosynthesis of lanosterol and desmosterol also was demonstrated. The in vitro incorporation of [1-14C]acetate into cholesterol was inhibited during Wallerian degeneration. Instead, cholesteryl esters were labeled as the major sterol product. Such inhibition, however, was not observed in the adult Trembler nerve (Brain Res. 325, 21-27, 1985), which is presumed to be due to a primary metabolic disorder of Schwann cells. The cholesterol biosynthesis was gradually resumed in degenerated nerve by either regeneration of crush-injured nerve or reattachment of the transected nerve. These results suggest that cholesterol biosynthesis in peripheral nerve relies on the axon to provide necessary substrates. De novo synthesis appears to be one of the major sources of endoneurial cholesterol that forms and maintains peripheral nerve myelin.

  4. Cholesterol-independent effects of methyl-β-cyclodextrin on chemical synapses.

    Directory of Open Access Journals (Sweden)

    Kiel G Ormerod

    Full Text Available The cholesterol chelating agent, methyl-β-cyclodextrin (MβCD, alters synaptic function in many systems. At crayfish neuromuscular junctions, MβCD is reported to reduce excitatory junctional potentials (EJPs by impairing impulse propagation to synaptic terminals, and to have no postsynaptic effects. We examined the degree to which physiological effects of MβCD correlate with its ability to reduce cholesterol, and used thermal acclimatization as an alternative method to modify cholesterol levels. MβCD impaired impulse propagation and decreased EJP amplitude by 40% (P<0.05 in preparations from crayfish acclimatized to 14 °C but not from those acclimatized to 21 °C. The reduction in EJP amplitude in the cold-acclimatized group was associated with a 49% reduction in quantal content (P<0.05. MβCD had no effect on input resistance in muscle fibers but decreased sensitivity to the neurotransmitter L-glutamate in both warm- and cold-acclimatized groups. This effect was less pronounced and reversible in the warm-acclimatized group (90% reduction in cold, P<0.05; 50% reduction in warm, P<0.05. MβCD reduced cholesterol in isolated nerve and muscle from cold- and warm-acclimatized groups by comparable amounts (nerve: 29% cold, 25% warm; muscle: 20% cold, 18% warm; P<0.05. This effect was reversed by cholesterol loading, but only in the warm-acclimatized group. Thus, effects of MβCD on glutamate-sensitivity correlated with its ability to reduce cholesterol, but effects on impulse propagation and resulting EJP amplitude did not. Our results indicate that MβCD can affect both presynaptic and postsynaptic properties, and that some effects of MβCD are unrelated to cholesterol chelation.

  5. Hypoxanthine induces cholesterol accumulation and incites atherosclerosis in apolipoprotein E-deficient mice and cells.

    Science.gov (United States)

    Ryu, Hye-Myung; Kim, You-Jin; Oh, Eun-Joo; Oh, Se-Hyun; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Park, Sun-Hee; Kim, Yong-Lim

    2016-11-01

    Reactive oxygen species (ROS) generation during purine metabolism is associated with xanthine oxidase and uric acid. However, the direct effect of hypoxanthine on ROS generation and atherosclerosis has not been evaluated. Smoking and heavy drinking are associated with elevated levels of hypoxanthine. In this study, we investigated the role of hypoxanthine on cholesterol synthesis and atherosclerosis development, particularly in apolipoprotein E (APOE)-deficient mice. The effect of hypoxanthine on the regulation of cholesterol synthesis and atherosclerosis were evaluated in Apoe knockout (KO) mice and cultured HepG2 cells. Hypoxanthine markedly increased serum cholesterol levels and the atherosclerotic plaque area in Apoe KO mice. In HepG2 cells, hypoxanthine increased intracellular ROS production. Hypoxanthine increased cholesterol accumulation and decreased APOE and ATP-binding cassette transporter A1 (ABCA1) mRNA and protein expression in HepG2 cells. Furthermore, H2 O2 also increased cholesterol accumulation and decreased APOE and ABCA1 expression. This effect was partially reversible by treatment with the antioxidant N-acetyl cysteine and allopurinol. Hypoxanthine and APOE knockdown using APOE-siRNA synergistically induced cholesterol accumulation and reduced APOE and ABCA1 expression. Hypoxanthine induces cholesterol accumulation in hepatic cells through alterations in enzymes that control lipid transport and induces atherosclerosis in APOE-deficient cells and mice. These effects are partially mediated through ROS produced in response to hypoxanthine. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. 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....

  7. CHOBIMALT: a cholesterol-based detergent.

    Science.gov (United States)

    Howell, Stanley C; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M; Sanders, Charles R

    2010-11-01

    Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3−4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1.

  8. Serum cholesterol in healthy postmenopausal women.

    Science.gov (United States)

    Samanta, B B

    1998-05-01

    Hypercholes erolaemia is a modifiable risk factor in atherosclerosis. Women lose their relative protection against coronory heart disease at menopause because of changed lipid profile due to oestrogen deficiency. Total serum cholesterol was estimated in 82 healthy postmenopausal women in the age group of 46-72 years (51.5 +/- 7.39). Thirty five healthy pre-menopausal women in the age group of 18-38 years (29.5 +/- 6.4) served as controls. The mean serum cholesterol concentration was significantly higher in the postmenopausal group compared to control group (178.5 +/- 39.8 Vs 155.4 +/- 24 mg/dl; P < 0.01). Serum cholesterol concentration in the study group was not related to social class, dietary habit and obesity.

  9. Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

    Directory of Open Access Journals (Sweden)

    Santhosh Karanth

    2013-11-01

    Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr, despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr.

  10. Phosphorylation regulates activity of 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme of cholesterol synthesis.

    Science.gov (United States)

    Prabhu, Anika V; Luu, Winnie; Sharpe, Laura J; Brown, Andrew J

    2017-01-01

    Cholesterol is essential for survival, but too much or too little can cause disease. Thus, cholesterol levels must be kept within close margins. 7-dehydrocholesterol reductase (DHCR7) is a terminal enzyme of cholesterol synthesis, and is essential for embryonic development. Largely, DHCR7 research is associated with the developmental disease Smith-Lemli-Opitz syndrome, which is caused by mutations in the DHCR7 gene. However, little is known about what regulates DHCR7 activity. Here we provide evidence that phosphorylation plays a role in controlling DHCR7 activity, which may provide a means to divert flux from cholesterol synthesis to vitamin D production. DHCR7 activity was significantly decreased when we used pharmacological inhibitors against two important kinases, AMP-activated protein kinase and protein kinase A. Moreover, mutating a known phosphorylated residue, S14, also decreased DHCR7 activity. Thus, we demonstrate that phosphorylation modulates DHCR7 activity in cells, and contributes to the overall synthesis of cholesterol, and probably vitamin D. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol o

  12. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

  13. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

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

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  14. Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

    Science.gov (United States)

    Iannella, Giannicola; Di Gioia, Cira; Carletti, Raffaella; Magliulo, Giuseppe

    2017-08-01

    This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. Retrospective study. Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. 3b. Laryngoscope, 127:E283-E290, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  15. The use of a food supplement is associated with changes in total cholesterol levels in adult women

    Directory of Open Access Journals (Sweden)

    Nelson Rodrigues Tavares

    2015-12-01

    Full Text Available High levels of total cholesterol are a significant risk factor for cardiovascular disease. An oral formulation comprised of two types of capsules was tested in adult women (n = 14 with total cholesterol values >200 mg/dL. In the first capsule were red yeast rice extract, pyridoxine hydrochloride, riboflavin, pteroylglutamic acid and cyanocobalamin, and in the second, a mixture of fish oils containing docosahexaenoic acid and eicosapentaenoic acid. After four weeks of supplementation, a significant (p =0.001 decrease was observed in the mean values of total cholesterol.

  16. [Basic mechanisms: absorption and excretion of cholesterol and other sterols].

    Science.gov (United States)

    Cofan Pujol, Montserrat

    2014-01-01

    Cholesterol is of vital importance for vertebrate cell membrane structure and function. It is obvious that adequate regulation of cholesterol homeostasis is essential. Hypercholesterolemia promotes atherosclerosis and thereby represents a major risk factor for cardiovascular disease. The liver has been considered the major site of control in maintenance of cholesterol homeostasis. The liver facilitates clearance of (very) low density lipoprotein particles and cholesterol-containing chylomicron remnants, synthesizes cholesterol, synthesizes and secretes (nascent) high density lipoprotein particles, secretes cholesterol and bile salts to bile, and is involved in reverse cholesterol transport. In recent years, however, the importance of the intestine in many aspects of cholesterol physiology is increasingly recognized. It has become apparent that direct secretion of cholesterol from the blood compartment into the intestine, or transintestinal cholesterol excretion, plays a major role in disposal of cholesterol via the feces. This review will discuss current knowledge on the physiology of cholesterol homeostasis, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and therapeutic options for hypercholesterolemia. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  17. Cholesterol Content of Tiger Shrimp Penaeus monodon at Various Sizes, Moulting and Maturity Stages from Pazhayar Coast (South East Coast of India

    Directory of Open Access Journals (Sweden)

    D. Kannan

    2014-01-01

    Full Text Available A quantitative study was made on the occurrence of cholesterol in the muscle of different maturity stages of the wilder tiger shrimp Penaeus monodon collected from Pazhayar coast, Nagapattinam, Tamil Nadu. As the size increased from 8-10 cm to 14-16 cm the cholesterol content increased from 1.4-4.5 mg g-1. The shrimp contained almost the same level of cholesterol in both sexes. The variation in the cholesterol level in relation to moulting in the male and female shrimp revealed that in both the sexes high cholesterol content was noticed in the intermoult stage. Subsequently, in the premoult stage the cholesterol content decreased from 2.0-1.8 mg g-1 and it was found to be the lowest among all the moult stages. In the matured stages the shrimp contained higher level of cholesterol (2.1 mg g-1 and very less amount of cholesterol level (1.2 mg g-1 in the immature and early mature stages. It is inferred from this study that the cholesterol level was more in the intermoult stage suggesting that cholesterol may be converted to some moulting hormones.

  18. [A history and review of cholesterol ester transfer protein inhibitors and their contribution to the understanding of the physiology and pathophysiology of high density lipoprotein].

    Science.gov (United States)

    Corral, Pablo; Schreier, Laura

    2014-01-01

    There is irrefutable evidence that statins reduce the risk of cardiovascular events in a magnitude proportional to the intensity of the decrease in cholesterol transport by the low density lipoproteins. Despite this great advance there is still a residual risk of cardiovascular events. For this reason, an increase in the levels of high density lipoprotein is considered in order to boost the main action of this lipoprotein, which is reverse cholesterol transport. Distinct classes of evidence (epidemiological, genetic, and pathophysiological) show that the inhibition and/or modulation of cholesterol ester transfer protein increases plasma high density lipoprotein-cholesterol levels. The main reason for presenting this review is to look at the physiology of cholesterol ester transfer protein, its interrelationship with high density lipoproteins, and to give an update on the development of different cholesterol ester transfer protein inhibitor/modulator molecules. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  19. 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...

  20. 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...

  1. Comparison of yolk fatty acid content, blood and egg cholesterol of ...

    African Journals Online (AJOL)

    The KFO diets reduced the blood cholesterol, yolk linoleic acid and yolk ω-6 FA ... a decrease and an increase in the ratio of ω-6/ ω-3 FAs (P<0.05), respectively. ... olein oil (POO), Kilka fish oil (KFO), hens, egg omega-9 and omega-3 fatty acid.

  2. 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.

  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. Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts.

    Science.gov (United States)

    Kim, Sangmin; Oh, Jang-Hee; Lee, Youngae; Lee, Jeongyoon; Cho, Kwang Hyun; Chung, Jin Ho

    2010-01-31

    Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (>or=200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.

  5. Macrophage specific caspase-1/11 deficiency protects against cholesterol crystallization and hepatic inflammation in hyperlipidemic mice.

    Directory of Open Access Journals (Sweden)

    Tim Hendrikx

    Full Text Available While non-alcoholic steatohepatitis (NASH is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr(-/- mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation.Ldlr (-/- mice were transplanted (tp with wild-type (Wt or caspase-1/11(-/- (dKO bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM from wt or caspase-1/11(-/- mice were incubated with oxLDL for 24h and autophagy was assessed.In line with our hypothesis, caspase-1/11(-/--tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11(-/--tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11(-/- mice had normal autophagy activity.Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed

  6. Plasma hormones, metabolites, milk production, and cholesterol levels in Murrah buffaloes fed with Asparagus racemosus in transition and postpartum period.

    Science.gov (United States)

    Singh, Surendra Pratap; Mehla, Ram Kumar; Singh, Mahendra

    2012-12-01

    Ten dry and pregnant Murrah buffaloes were selected to investigate the effect of Asparagus racemosus feeding on hormones, metabolites, milk yield, and plasma cholesterol levels. The treatment groups of buffaloes were fed with A. racemosus (shatavari) @ 150 g/day/animal during prepartum and @ 300 g/day/animal during the postpartum period. Blood samples collected on -6, -4, -2-week, day of parturition (0), and +2, +4, and +6-week postpartum were analyzed for plasma total cholesterol, triglycerides, HDL, low-density lipoproteins (LDL), prolactin, cortisol, and blood metabolites. Milk samples collected at weekly intervals (+1, +3, +5, and 7 weeks) were analyzed for total milk fat cholesterol. Prepartum plasma cholesterol concentrations were significantly higher in treatment group over the control (P < 0.05). Mean plasma triglycerides, LDL cholesterol, HDL cholesterol, glucose, and nonesterified fatty acid (NEFA) levels varied nonsignificantly between groups. Plasma prolactin and cortisol concentrations were significantly (P < 0.01) more in treatment group than in control group. On day of parturition, plasma prolactin, cortisol, LDL, and plasma total cholesterol were higher (P < 0.01) in treatment group buffaloes in comparison to control group. A. racemosus feeding significantly (P < 0.01) increased plasma prolactin, cortisol (P < 0.01), and milk fat cholesterol (P < 0.05) without affecting total cholesterol, HDL, LDL, glucose, and NEFA concentrations. The buffaloes of treatment group produced more milk (@ 0.526 kg/animal/day) suggesting thereby that A. racemosus is galactopoietic. It was concluded that feeding of A. racemosus increases plasma prolactin and cortisol and decreased plasma total cholesterol and LDL concentration.

  7. 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.

  8. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

    Science.gov (United States)

    Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

    2017-06-01

    Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis.

    Science.gov (United States)

    Pandak, W M; Schwarz, C; Hylemon, P B; Mallonee, D; Valerie, K; Heuman, D M; Fisher, R A; Redford, K; Vlahcevic, Z R

    2001-10-01

    The initial and rate-limiting step in the classic pathway of bile acid biosynthesis is 7alpha-hydroxylation of cholesterol, a reaction catalyzed by cholesterol 7alpha-hydroxylase (CYP7A1). The effect of CYP7A1 overexpression on cholesterol homeostasis in human liver cells has not been examined. The specific aim of this study was to determine the effects of overexpression of CYP7A1 on key regulatory steps involved in hepatocellular cholesterol homeostasis, using primary human hepatocytes (PHH) and HepG2 cells. Overexpression of CYP7A1 in HepG2 cells and PHH was accomplished by using a recombinant adenovirus encoding a CYP7A1 cDNA (AdCMV-CYP7A1). CYP7A1 overexpression resulted in a marked activation of the classic pathway of bile acid biosynthesis in both PHH and HepG2 cells. In response, there was decreased HMG-CoA-reductase (HMGR) activity, decreased acyl CoA:cholesterol acyltransferase (ACAT) activity, increased cholesteryl ester hydrolase (CEH) activity, and increased low-density lipoprotein receptor (LDLR) mRNA expression. Changes observed in HMGR, ACAT, and CEH mRNA levels paralleled changes in enzyme specific activities. More specifically, LDLR expression, ACAT activity, and CEH activity appeared responsive to an increase in cholesterol degradation after increased CYP7A1 expression. Conversely, accumulation of the oxysterol 7alpha-hydroxycholesterol in the microsomes after CYP7A1 overexpression was correlated with a decrease in HMGR activity.

  10. Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the golden Syrian hamster.

    Science.gov (United States)

    Burke, Katie T; Colvin, Perry L; Myatt, Leslie; Graf, Gregory A; Schroeder, Friedhelm; Woollett, Laura A

    2009-06-01

    The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by the placenta, and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possibly 3) increased placental NPC1L1 expression.

  11. Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy.

    Directory of Open Access Journals (Sweden)

    Koushik Roy

    2016-05-01

    Full Text Available Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ of Leishmania donovani (LD infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation.MΦ of CBA/j mice were infected with Leishmania donovani (I-MΦ. Two different anti-Aκ mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5-2 was conformation specific, whereas the other one (10.2.16 was not. Under parasitized condition, the binding of 11.5-2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5-2 was restored to normal upon liposomal delivery of cholesterol in I-MΦ. By molecular dynamics (MD simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-MΦ.The decrease in membrane cholesterol in I-MΦ may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of the peptide. Furthermore, liposomal delivery of

  12. Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides.

    Science.gov (United States)

    Wada, Shunsuke; Yasuhara, Hidenori; Wada, Fumito; Sawamura, Motoki; Waki, Reiko; Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Obika, Satoshi

    2016-03-28

    Cholesterol conjugation of oligonucleotides is an attractive way to deliver the oligonucleotides specifically to the liver. However cholesterol-conjugated antisense oligonucleotides (ASOs) mainly accumulate in non-parenchymal cells (NPCs) such as Kupffer cells. In this study, to increase the hepatic accumulation of cholesterol-conjugated ASOs, we prepared a variety of linkers for cholesterol conjugation to anti-Pcsk9 ASOs and examined their effects on pharmacological parameters. Hepatic accumulation of ASO was dramatically increased with cholesterol conjugation. The increase in hepatic accumulation depended largely on the linker chemistry of each cholesterol-conjugated ASO. In addition to hepatic accumulation, the cell tropism of each cholesterol-conjugated ASO tended to depend on their linker. Although a linker bearing a disulfide bond accumulated mainly in NPCs, hexamethylene succinimide linker accumulated mainly in hepatocytes. To estimate the benefits of releasing ASO from the conjugated cholesterol in hepatocyte, we designed another linker based on hexamethylene succinimide, which has a phosphodiester bond between the linker and the ASO. The cholesterol-conjugated ASO bearing such a phosphodiester bond showed a significantly improved Pcsk9 mRNA inhibitory effect compared to its counterpart, cholesterol-conjugated ASO with a phosphorothioate bond, while the hepatic accumulation of both cholesterol-conjugated ASOs was comparable, indicating the effectiveness of removing the conjugated cholesterol for ASO activity. In toxicity analysis, some of the linkers induced lethal toxicities when they were injected at high concentrations (>600μM). These toxicities were attributed to decreased platelet levels in the blood, suggesting an interaction between cholesterol-conjugated ASO and platelets. Our findings may provide a guideline for the design of molecule-conjugated ASOs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

    Science.gov (United States)

    Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

    2017-04-01

    Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m(2)) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Digital gene-expression profiling analysis of the cholesterol-lowering effects of alfalfa saponin extract on laying hens.

    Directory of Open Access Journals (Sweden)

    Lu Zhou

    Full Text Available BACKGROUND: To prevent cardiovascular disease, people are advised to limit their intake of dietary cholesterol to less than 300 mg/day. Egg consumption has been seriously reduced because of the high levels of cholesterol. The purpose of the present study was to evaluate the cholesterol-lowering effects of alfalfa saponin extract (ASE in yolk and the molecular mechanisms underlying these effects using digital gene-expression profiling analysis. Liver and ovary tissues were isolated from laying hens fed with ASE for RNA sequencing. RESULTS: The cholesterol content of the yolks of eggs from hens fed 120 mg/kg ASE declined considerably on day 60. Other groups (60, 240, 480 mg/kg ASE group also showed decreases, but they were not significant. Digital gene expression generated over nine million reads per sample, producing expression data for least 12,384 genes. Among these genes, 110 genes showed greater than normal expression in the liver and 107 genes showed greater than normal expression in the ovary. Cholesterol 7 alpha-hydroxylase (Cyp7a1 and apolipoprotein H (Apoh, which act in the synthesis of bile acid and cholesterol efflux, showed more expression in the livers of hens given dietary ASE supplementation. In the ovary, levels of very low density lipoprotein receptor (Vldlr, apolipoprotein B (Apob, apovitellenin 1 (ApovldlII and vitellogenin (VtgI, VtgII and VtgIII in ovary decreased with dietary ASE supplementation. CONCLUSION: Transcriptome analysis revealed that the molecular mechanisms underlying the cholesterol-lowering effects of ASE were partially mediated by enhancement of cholesterol efflux in the liver and this reduced of cholesterol deposition in the ovary.

  15. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  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. Cholesterol levels in fragile X syndrome.

    Science.gov (United States)

    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.

  18. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two...

  19. 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

  20. Degradation of cholesterol crystals in phospholipids

    Science.gov (United States)

    Koren, Eugen; Koscec, Mirna; Fugate, Robert D.

    1993-02-01

    Based on previous studies from the laboratory that demonstrated degradation of cholesterol crystals ingested by macrophages in a cell culture system and indicated that intracellular phospholipids could play an important role in mobilization of crystalline cholesterol, the role of each of the three major intracellular phospholipid species in degradation of crystals is further explored. Fluorescently labeled cholesterol crystals are incubated with phospholipids over a period of 5 d. Morphological changes in crystals are monitored using digital imaging fluorescence microscopy, fluorescence redistribution after photobleaching, confocal microscopy, and epifluorescent and phase contrast microscopy. Results clearly demonstrate that all three phospholipids are able to mobilize crystalline cholesterol. However, the mechanisms by which they exert mobilization are different. Sphingomyelin and phosphatidylchloline are found to cause gradual and uniform dissolution of crystals, more or less preserving their original shape. Phosphatidylethanolamine appear to penetrate into the crystal, causing its fragmentation and solubilization. In the mixture of all three phospholipids representing the composition found in macrophages, both of the described mechanisms are working simultaneously.

  1. Garbanzo diet lowers cholesterol in hamsters

    Science.gov (United States)

    Cholesterol-lowering potential of diets with 22% protein from Chickpea (Cicer arietinum, European variety of Garbanzo, Kabuli Chana), Bengal gram (Cicer arietinum, Asian variety of Garbanzo, Desi Chana, smaller in size, yellow to black color), lentils, soy protein isolate, hydrolyzed salmon protein...

  2. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    May 18, 2009 ... human nutrition in Africa, Asia and Latin America. They are an important resource for the natives of Southern. Nigeria, who like other indigenous groups, expend much ... times adults variety of winged termites, bees, wasp and ant brood (larvae .... exerts remarkable influence on their lipid and cholesterol.

  3. Cardiovascular disease markers responses in male receiving improved-fat meat-products vary by initial LDL-cholesterol levels.

    Directory of Open Access Journals (Sweden)

    Paloma Celada

    2016-11-01

    Full Text Available Objectives: Cardiovascular disease (CVD is prevalent in people at high meat-product consumption. To study the effect of consuming different Pâté and Frankfurter formulations on clinical/emergent CVD biomarkers in male volunteers with different initial LDL-cholesterol levels (< and ³ 3.36 mmol/L. Method: Eighteen male volunteers with at least two CVD risk factors were enrolled in a crossover controlled study. Pork-products were consumed during 4wk: reduced-fat (RF, omega-3-enriched-RF (n-3RF, and normal-fat (NF. Pork-products were separated by 4wk washout. Lipids, lipoproteins, oxidized LDL (oxLDL, apolipoproteins (apo and their ratios, homocysteine (tHcys, arylesterase (AE, C-reactive protein (CRP, tumor necrotic factor (TNFa were tested. Results: The rate of change for AE, oxLDL, Lp(a, AE/HDL-cholesterol, LDL/apo B and AE/oxLDL ratios varied (p<0.05 among periods only in volunteers with LDLcholesterol ³3.36 mmol/L. TNFa decreased (p<0.05 among volunteers with low-normal LDL-cholesterol values while AE increased (p<0.01 in high LDL-cholesterol volunteers during the RF-period. AE increased while CRP decreased (both p<0.01 in low-normal LDL-cholesterol volunteers while AE (p<0.001 and apo B (p<0.01 increased in the high LDL-cholesterol group during the n-3RF-period. Total cholesterol (p<0.05 increased in the low/normal LDL-cholesterol group while tHcys decreased (p<0.05 in the high LDL-cholesterol group during the NF-period. Differences in response in volunteers with low-normal vs. high initial LDL-cholesterol levels to the n-3RF but not to the RF meat-products seem evident. Conclusions: Subjects with high LDL-cholesterol seem target for n-3RF products while subjects with LDL-cholesterol <3.36 mmol/L were more negatively affected by NF-products. Any generalization about functional meat product or consumption should be avoided.

  4. In vitro and in vivo cholesterol lowering ability of Lactobacillus pentosus KF923750.

    Science.gov (United States)

    Bendali, F; Kerdouche, K; Hamma-Faradji, S; Drider, D

    2017-03-16

    Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.

  5. Marked inhibition of hepatic cytochrome P450 activity in cholesterol-induced atherosclerosis in rabbits.

    Science.gov (United States)

    Irizar, A; Ioannides, C

    1998-04-03

    The objective of the present study was to investigate the expression of major xenobiotic-metabolising cytochrome P450 proteins, and of other enzyme systems, in hepatic and extrahepatic tissues of rabbits rendered atherosclerotic by the dietary administration of 1% cholesterol diets for 8 weeks. Individual cytochrome P450 proteins were monitored using diagnostic substrates and immunologically in Western blot analysis. The activity of all hepatic isoforms studied was depressed in the atherosclerotic animals; when, however, apoprotein levels were determined immunologically, no major differences were evident between the control and the atherosclerotic rabbits. In vitro studies indicated that neither cholesterol nor palm oil inhibited cytochrome P450 activity. The effects of cholesterol treatment leading to atherosclerosis on kidney, heart and lung cytochrome P450 activities were isoform- and tissue-specific; no change was evident in the heart activities, but in the lung and kidney cytochrome P450 activities were clearly modulated by the treatment with cholesterol. Apoprotein levels did not always parallel the changes in activities. Western blot analysis of aortic cytochromes P450 revealed that administration of cholesterol-rich diets enhanced CYP2B and CYP3A apoprotein levels. Cholesterol feeding to rabbits gave rise to a marked decrease in hepatic glutathione S-transferase activity but did not influence glutathione reductase or total glutathione levels. The same treatment had no effect on catalase, glutathione peroxidase and superoxide dismutase. It is concluded that treatment of rabbits with cholesterol-rich diets leading to atherosclerosis gives rise to profound changes in the expression of cytochrome P450 proteins in the liver and other tissues; possible mechanisms are discussed.

  6. Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

    Directory of Open Access Journals (Sweden)

    Bon Jeong Ku

    Full Text Available The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6 is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+Mig-6(f/f; Mig-6(d/d. Mig-6(d/d mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d mice compared to Mig-6(f/f controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.

  7. HDL cholesterol: reappraisal of its clinical relevance.

    Science.gov (United States)

    März, Winfried; Kleber, Marcus E; Scharnagl, Hubert; Speer, Timotheus; Zewinger, Stephen; Ritsch, Andreas; Parhofer, Klaus G; von Eckardstein, Arnold; Landmesser, Ulf; Laufs, Ulrich

    2017-03-24

    While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted. This review article is based on a selective literature review. In individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes. In contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.

  8. Extracts of Edible Plants Inhibit Pancreatic Lipase, Cholesterol Esterase and Cholesterol Micellization, and Bind Bile Acids

    Directory of Open Access Journals (Sweden)

    Julnaryn Intrawangso

    2012-01-01

    Full Text Available The application of edible plants with more effective ability to inhibit fat digestion and absorption has recently been explored for possible treatment of hyperlipidaemia. The aim of the present study is to investigate the effect of nine edible plants on the inhibition of pancreatic lipase and pancreatic cholesterol esterase activities, as well as the inhibition of cholesterol micelle formation, and bile acid binding. Our findings have shown strong pancreatic lipase inhibitory activity and the inhibition of cholesterol micellization by mulberry leaf extract. Safflower extract was the most potent inhibitor of pancreatic cholesterol esterase. In addition, cat’s whiskers and safflower extracts had a potent bile acid binding activity. It is suggested that a daily intake of these edible plants may delay postprandial hypertriacylglycerolaemia and hypercholesterolaemia, and therefore may be applied for the prevention and treatment of hyperlipidaemia.

  9. CHOLESTEROL BIOTRANSFORMATION TO CHOLESTA-4, 6-DIEN-3-OL AND EFFECT OF ASSIMILATION ON ADHESION PROPERTIES OF LACTOBACILLUS HELVETICUS CD6

    Directory of Open Access Journals (Sweden)

    Jayesh J. Ahire

    2014-04-01

    Full Text Available Cholesterol biotransformation by Lactobacillus helveticus CD6 was observed in minimal medium supplemented with 3 mM cholesterol when grown for 120 h at 37 °C. Its gas chromatography-mass spectrometry (GC-MS showed production of cholesta-4, 6-dien-3-ol and cholest-5-en-3-ol (3.beta with 12 U ∕mg cholesterol oxidase-like enzyme activity. The cholesterol assimilation was evaluated at varied concentrations of bile salt in MRS medium. The cell survival and cholesterol assimilation was found to be adversely affected in presence of bile salt. Microscopic studies revealed changed cell morphology when grown with cholesterol. The cell adhesion properties like autoaggregation, microbial adhesion to solvents where found to be affected by cholesterol. The 7.49 % cell adhesion to ethyl acetate indicates the decrease in electron accepting properties of cell surface, while 9 % decrease in xylene adhesion and 13 % decrease in autoaggregation was observed which would be helpful in cholesterol lowering when supplemented in the form of probiotic preparation.

  10. High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol.

    Science.gov (United States)

    Tosheska Trajkovska, Katerina; Topuzovska, Sonja

    2017-08-01

    A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT pathway consists of the following steps: 1. Cholesterol efflux from peripheral tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease.

  11. 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....

  12. Estimating the burden of disease attributable to high cholesterol in ...

    African Journals Online (AJOL)

    burden attributed to high cholesterol for the four population ... and Women's Hospital, Harvard Medical Sclwol, Boston, USA ..... deaths and disability. ..... Executive Summary of the Third Report of the National Cholesterol Education Program.

  13. Trans Fat Now Listed With Saturated Fat and Cholesterol

    Science.gov (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  14. 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...

  15. Are You Taking the Right Treatment for Your High Cholesterol?

    Science.gov (United States)

    ... you taking the right treatment for your high cholesterol? Our analysis and new guidelines could change your ... people consider a moderate-intensity statin (reduces LDL cholesterol by 30 percent to 50 percent) • People 40 ...

  16. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  17. CDC Vital Signs: High Blood Pressure and Cholesterol

    Science.gov (United States)

    ... the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook Tweet Share ... cdc.gov/GISCVH2/ High Blood Pressure and High Cholesterol Among US Adults SOURCES: National Health and Nutrition ...

  18. 1 in 7 Obese People Has Normal Blood Pressure, Cholesterol

    Science.gov (United States)

    ... in 7 Obese People Has Normal Blood Pressure, Cholesterol But that doesn't mean the excess weight ... people studied, 14 percent had normal blood sugar, cholesterol and blood pressure readings, the study found. Doctors ...

  19. Cholesterol paradox: a correlate does not a surrogate make.

    Science.gov (United States)

    DuBroff, Robert

    2017-03-01

    The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.

  20. 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.