Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.

PubMed

Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G; Guizzetti, Marina

2014-11-01

Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cholesterol efflux and decreased cholesterol content in astrocytes in vitro. In the present study we investigated whether similar effects could be seen in vivo. Pregnant Sprague-Dawley rats were fed liquid diets containing 36% of the calories from ethanol from gestational day (GD) 6 to GD 21. A pair-fed control groups and an ad libitum control group were included in the study. ABCA1 and ABCG1 protein expression and cholesterol and phospholipid levels were measured in the neocortex of female and male fetuses at GD 21. Body weights were decreased in female fetuses as a consequence of ethanol treatments. ABCA1 and ABCG1 protein levels were increased, and cholesterol levels were decreased, in the neocortex of ethanol-exposed female, but not male, fetuses. Levels of phospholipids were unchanged. Control female fetuses fed ad libitum displayed an up-regulation of ABCA1 and a decrease in cholesterol content compared with pair-fed controls, suggesting that a compensatory up-regulation of cholesterol levels may occur during food restriction. Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters' expression and reducing brain cholesterol levels. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

PubMed Central

2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of acyl-CoA:cholesterol acyltransferase (ACAT) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1). Conclusion This study suggested that the two NS lactobacillus strains may affect lipid metabolism and have cholesterol-lowering effects in rats fed a high cholesterol diet. PMID:23656797

Fish protein hydrolysates affect cholesterol metabolism in rats fed non-cholesterol and high-cholesterol diets.

PubMed

Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

2012-03-01

Fish consumption is well known to provide health benefits in both experimental animals and human subjects. Numerous studies have demonstrated the beneficial effects of various protein hydrolysates on lipid metabolism. In this context, this study examined the effect of fish protein hydrolysates (FPH) on cholesterol metabolism compared with the effect of casein. FPHs were prepared from Alaska pollock meat using papain as a protease. Male Wistar rats were divided into the following four dietary groups of seven rats each: either casein (20%) or FPH (10%) + casein (10%), with or without 0.5% cholesterol and 0.1% sodium cholate. Serum and liver lipid levels, fecal cholesterol and bile acid excretions, and the hepatic expression of genes encoding proteins involved in cholesterol homeostasis were examined. In rats fed the FPH diets compared with casein diets with or without cholesterol and sodium cholate, the indexes of cholesterol metabolism-namely, serum cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels-were significantly lower, whereas fecal cholesterol and bile acid excretions were higher. Rats fed the FPH diets compared with casein with cholesterol exhibited a lower liver cholesterol level via an increased liver cholesterol 7α-hydroxylase (CYP7A1) expression level. This study demonstrates that the intake of FPH has hypocholesterolemic effects through the enhancement of fecal cholesterol and bile acid excretions and CYP7A1 expression levels. Therefore, fish peptides prepared by papain digestion might provide health benefits by decreasing the cholesterol content in the blood, which would contribute to the prevention of circulatory system diseases such as arteriosclerosis.

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

PubMed

Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui

2016-03-08

Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

A Statistical Study of Serum Cholesterol Level by Gender and Race.

PubMed

Tharu, Bhikhari Prasad; Tsokos, Chris P

2017-07-25

Cholesterol level (CL) is growing concerned as health issue in human health since it is considered one of the causes in heart diseases. A study of cholesterol level can provide insight about its nature and characteristics. A cross-sectional study. National Health and Nutrition Examination Survey (NHANS) II was conducted on a probability sample of approximately 28,000 persons in the USA and cholesterol level is obtained from laboratory results. Samples were selected so that certain population groups thought to be at high risk of malnutrition. Study included 11,864 persons for CL cases with 9,602 males and 2,262 females with races: whites, blacks, and others. Non-parametric statistical tests and goodness of fit test have been used to identify probability distributions. The study concludes that the cholesterol level exhibits significant racial and gender differences in terms of probability distributions. The study has concluded that white people are relatively higher at risk than black people to have risk line and high risk cholesterol. The study clearly indicates that black males normally have higher cholesterol. Females have lower variation in cholesterol than males. There exists gender and racial discrepancies in cholesterol which has been identified as lognormal and gamma probability distributions. White individuals seem to be at a higher risk of having high risk cholesterol level than blacks. Females tend to have higher variation in cholesterol level than males.

Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

PubMed

Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

2016-05-01

Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this approach for atherosclerosis regression. © The Author(s) 2015.

Step by Step: Eating To Lower Your High Blood Cholesterol. Revised.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

This booklet offers advice for adults who want to lower their blood cholesterol level. The first section, "What You Need To Know about High Blood Cholesterol," discusses blood cholesterol and why it matters, what cholesterol numbers mean, and what affects blood cholesterol levels. Section 2, "What You Need To Do To Lower Blood…

75 FR 28841 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-24

... Change To Amend FINRA Rule 6121 (Trading Halts Due to Extraordinary Market Volatility) May 19, 2010... Halts Due to Extraordinary Market Volatility) to permit FINRA to halt trading by FINRA members otherwise... October 2008, FINRA adopted FINRA Rule 6121 (Trading Halts Due to Extraordinary Market Volatility) to...

Nonlinear Associations between Plasma Cholesterol Levels and Neuropsychological Function

PubMed Central

Wendell, Carrington R.; Zonderman, Alan B.; Katzel, Leslie I.; Rosenberger, William F.; Plamadeala, Victoria V.; Hosey, Megan M.; Waldstein, Shari R.

2016-01-01

Objective Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Method Participants were 190 older adults (53% men, ages 54–83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed/dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. Results A significant quadratic effect of total cholesterol2 × age was identified for Logical Memory II (b=−.0013, p=.039), such that the 70+ group performed best at high and low levels of total cholesterol than at mid-range total cholesterol (U-shaped), and the <70 group performed worse at high and low levels of total cholesterol than at mid-range total cholesterol (inverted U-shape). Similarly, significant U- and J-shaped effects of LDL cholesterol2 × age were identified for Visual Reproduction II (b=−.0020, p=.026) and log of Trails B (b=.0001, p=.044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Conclusions Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. PMID:27280580

Characteristics of human hypo- and hyperresponders to dietary cholesterol.

PubMed

Katan, M B; Beynen, A C

1987-03-01

The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

The Effect of Deployment on Cholesterol Levels of Active Duty Personnel

DTIC Science & Technology

2006-05-01

fairly good results regarding cholesterol levels. It was noted that several members returned from deployment with elevated levels, sometimes to the...LDL cholesterol and low HDL cholesterol (Downs, John R., Beere, Polly A., Whitney, Edwin, Clearfield, Michael, Weis, Stephen, Rochen, Jeffrey, Stein...specific ages, including cholesterol screenings beginning at age 25. Given the age of the majority of this population, one might expect relatively good

Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

Studies have shown that high blood cholesterol levels play a role in the development of coronary heart disease in adults, and that the process leading to atherosclerosis begins in childhood. To address the problem of high cholesterol levels in children, the Panel on Blood Cholesterol Levels recommends complementary approaches for individuals and…

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

NASA Astrophysics Data System (ADS)

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-06-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

PubMed Central

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-01-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

PubMed

Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

2012-05-01

In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. Copyright © 2012 American Association for the Study of Liver Diseases.

Nonlinear associations between plasma cholesterol levels and neuropsychological function.

PubMed

Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

2016-11-01

Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. A significant quadratic effect of Total Cholesterol² × Age was identified for Logical Memory II ( b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol² × Age were identified for Visual Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

From Evolution to Revolution: miRNAs as Pharmacological Targets for Modulating Cholesterol Efflux and Reverse Cholesterol Transport

PubMed Central

Dávalos, Alberto; Fernández-Hernando, Carlos

2013-01-01

There has been strong evolutionary pressure to ensure that an animal cell maintain levels of cholesterol within tight limits for normal function. Imbalances in cellular cholesterol levels are a major player in the development of different pathologies associated to dietary excess. Although epidemiological studies indicate that elevated levels of high-density lipoprotein (HDL)-cholesterol reduce the risk of cardiovascular disease, recent genetic evidence and pharmacological therapies to raise HDL levels do not support their beneficial effects. Cholesterol efflux as the first and probably the most important step in reverse cholesterol transport is an important biological process relevant to HDL function. Small non-coding RNAs (microRNAs), post-transcriptional control different aspects of cellular cholesterol homeostasis including cholesterol efflux. miRNA families miR-33, miR-758, miR-10b, miR-26 and miR-106b directly modulates cholesterol efflux by targeting the ATP-binding cassette transporter A1 (ABCA1). Pre-clinical studies with anti-miR therapies to inhibit some of these miRNAs have increased cellular cholesterol efflux, reverse cholesterol transport and reduce pathologies associated to dyslipidemia. Although miRNAs as therapy have benefits from existing antisense technology, different obstacles need to be solved before we incorporate such research into clinical care. Here we focus on the clinical potential of miRNAs as therapeutic target to increase cholesterol efflux and reverse cholesterol transport as a new alternative to ameliorate cholesterol-related pathologies. PMID:23435093

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

PubMed Central

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

Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection.

PubMed

Serquiña, Anna K P; Kambach, Diane M; Sarker, Ontara; Ziegelbauer, Joseph M

2017-07-11

From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels. This suggests that multiple targets are needed to perturb this tightly regulated pathway. We also report here that cholesterol levels were decreased in de novo -infected HUVECs after 7 days. This reduction is at least partially due to viral miRNAs, since the mutant form of KSHV lacking 10 of the 12 miRNA genes had increased cholesterol compared to wild-type infections. We hypothesized that KSHV is downregulating cholesterol to suppress the antiviral response by a modified form of cholesterol, 25-hydroxycholesterol (25HC). We found that the cholesterol 25-hydroxylase (CH25H) gene, which is responsible for generating 25HC, had increased expression in de novo -infected HUVECs but was strongly suppressed in long-term latently infected cell lines. We found that 25HC inhibits KSHV infection when added exogenously prior to de novo infection. In conclusion, we found that multiple KSHV viral miRNAs target enzymes in the mevalonate pathway to modulate cholesterol in infected cells during latency. This repression of cholesterol levels could potentially be beneficial to viral infection by decreasing the levels of 25HC. IMPORTANCE A subset of viruses express unique microRNAs (miRNAs), which act like cellular miRNAs to generally repress host gene expression. A cancer virus, Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8 [HHV-8]), encodes multiple miRNAs that repress gene expression of multiple enzymes that are important for cholesterol synthesis. In cells with these viral miRNAs or with natural infection, cholesterol levels are reduced, indicating these viral miRNAs decrease cholesterol levels. A modified form of cholesterol, 25-hydroxycholesterol, is generated directly from cholesterol. Addition of 25-hydroxycholesterol to primary cells inhibited KSHV infection of cells, suggesting that viral miRNAs may decrease cholesterol levels to decrease the concentration of 25-hydroxycholesterol and to promote infection. These results suggest a new virus-host relationship and indicate a previously unidentified viral strategy to lower cholesterol levels. Copyright © 2017 Serquiña et al.

An R132H Mutation in Isocitrate Dehydrogenase 1 Enhances p21 Expression and Inhibits Phosphorylation of Retinoblastoma Protein in Glioma Cells

PubMed Central

Miyata, Satsuki; Urabe, Masashi; Gomi, Akira; Nagai, Mutsumi; Yamaguchi, Takashi; Tsukahara, Tomonori; Mizukami, Hiroaki; Kume, Akihiro; Ozawa, Keiya; Watanabe, Eiju

2013-01-01

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation. PMID:24077277

An R132H mutation in isocitrate dehydrogenase 1 enhances p21 expression and inhibits phosphorylation of retinoblastoma protein in glioma cells.

PubMed

Miyata, Satsuki; Urabe, Masashi; Gomi, Akira; Nagai, Mutsumi; Yamaguchi, Takashi; Tsukahara, Tomonori; Mizukami, Hiroaki; Kume, Akihiro; Ozawa, Keiya; Watanabe, Eiju

2013-01-01

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1(R132H)-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1(R132H)-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progression of the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.

BMI, body fat mass and plasma leptin level in relation to cardiovascular diseases risk factors among adolescents in Taitung.

PubMed

Wu, Ya-Ke; Chu, Nain-Feng; Huang, Ya-Hsien; Syu, Jhu-Ting; Chang, Jin-Biou

2016-01-01

To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Potential Mechanisms Leading to the Abnormal Lipid Profile in Patients With Rheumatoid Arthritis Versus Healthy Volunteers and Reversal by Tofacitinib†, ‡

PubMed Central

Fleischmann, Roy; Davignon, Jean; Schwartz, Howard; Turner, Scott M.; Beysen, Carine; Milad, Mark; Hellerstein, Marc K.; Luo, Zhen; Kaplan, Irina V.; Riese, Richard; Zuckerman, Andrea; McInnes, Iain B.

2015-01-01

Objective Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Systemic inflammation is proposed to play a fundamental role in the altered lipid metabolism associated with RA; however, the underlying mechanisms are unknown. We undertook this study to compare cholesterol and lipoprotein kinetics in patients with active RA with those in matched healthy volunteers. Methods This was a phase I open‐label mechanism‐of‐action study. Cholesterol and lipoprotein kinetics were assessed with 13C‐cholesterol and 13C‐leucine infusions. RA patients were reevaluated after receiving oral tofacitinib 10 mg twice daily for 6 weeks. Results Levels of high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, total cholesterol, and apolipoprotein A‐I (Apo A‐I) as well as HDL cholesterol particle number were lower in RA patients (n = 36) than in healthy volunteers (n = 33). In contrast, the cholesterol ester fractional catabolic rate was higher in RA patients, but no differences were observed in cholesterol ester transfer protein, cholesterol ester production rate, HDL‐associated Apo A‐I fractional catabolic rate, or LDL‐associated Apo B fractional catabolic rate. Following tofacitinib treatment in RA patients, the cholesterol ester fractional catabolic rate decreased and cholesterol levels increased. The decrease in cholesterol ester fractional catabolic rate correlated significantly with the increase in HDL cholesterol. Additionally, HDL cholesterol particle number increased and markers of HDL cholesterol function improved. Conclusion This is the first study to assess cholesterol and lipoprotein kinetics in patients with active RA and matched healthy volunteers. The data suggest that low cholesterol levels in patients with active RA may be driven by increases in cholesterol ester catabolism. Tofacitinib treatment reduced cholesterol ester catabolism, thereby increasing cholesterol levels toward those in healthy volunteers, and markers of antiatherogenic HDL function improved. PMID:25470338

Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

PubMed

Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

2015-01-01

This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p<0.05). Serum HDL cholesterol level tended to increase and hepatic total cholesterol level decreased and were comparable to the CON group (p>0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p<0.05). Serum and hepatic total cholesterol level, kidney, and body fat weights decreased, and were compared to the CON group (p>0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

Correlation between plasma component levels of cultured fish and resistance to bacterial infection

USGS Publications Warehouse

Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

1998-01-01

Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population.

PubMed

Segoviano-Mendoza, Marcela; Cárdenas-de la Cruz, Manuel; Salas-Pacheco, José; Vázquez-Alaniz, Fernando; La Llave-León, Osmel; Castellanos-Juárez, Francisco; Méndez-Hernández, Jazmín; Barraza-Salas, Marcelo; Miranda-Morales, Ernesto; Arias-Carrión, Oscar; Méndez-Hernández, Edna

2018-01-15

Cholesterol has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence about crucial requirement of neuron membrane cholesterol in the organization and function of the 5-HT 1A serotonin receptor. For this, low cholesterol level has been reported to be associated with depression and suicidality. However there have been inconsistent reports about this finding and the exact relationship between these factors remains controversial. Therefore, we investigated the link between serum cholesterol and its fractions with depression disorder and suicide attempt in 467 adult subjects in Mexican mestizo population. Plasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had undergone an episode of suicide attempt, and 206 healthy controls. A significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride serum levels was observed in the groups of MDD patients and suicide attempt compared to those without suicidal behavior (p < 0.05). After adjusting for covariates, lower cholesterol levels were significantly associated with MDD (OR 4.229 CI 95% 2.555 - 7.000, p<.001) and suicide attempt (OR 5.540 CI 95% 2.825 - 10.866, p<.001) CONCLUSIONS: These results support the hypothesis that lower levels of cholesterol are associated with mood disorders like MDD and suicidal behavior. More mechanistic studies are needed to further explain this association.

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

PubMed

Xie, Jiang; Guan, Fei; Wang, Jia-Hong; Hu, Da-Yi

2011-10-01

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

Statins - a role in breast cancer therapy?

PubMed

Borgquist, Signe; Bjarnadottir, Olöf; Kimbung, Siker; Ahern, Thomas P

2018-06-20

Statin drugs have been used for more than two decades to treat hypercholesterolemia and as cardio-preventive drugs, resulting in a marked decrease in cardiovascular morbidity and mortality worldwide. Statins halt hepatic cholesterol biosynthesis by inhibiting the rate-limiting enzyme in the mevalonate pathway, hydroxymethylglutaryl-coenzyme A reductase (HMGCR). The mevalonate pathway regulates a host of biochemical processes in addition to cholesterol production. Attenuation of these pathways is likely responsible for the myriad benefits of statin therapy beyond cholesterol reduction-the so-called pleiotropic effects of statins. Chief among these purported effects is anti-cancer activity. A considerable body of preclinical, epidemiologic, and clinical evidence shows that statins impair proliferation of breast cancer cells and reduce the risk of breast cancer recurrence. Potential mechanisms for this effect have been explored in laboratory models, but remain poorly understood and require further investigation. The number of clinical trials assessing the putative clinical benefit of statins in breast cancer is increasing. Currently, a total of 30 breast cancer/statin trials are listed at the global trial identifier website clinicaltrials. gov.Given the compelling evidence from performed trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant breast cancer setting. It would be imperative for such a trial to incorporate tumor biomarkers predictive of statin response in its design and analysis plan. Ongoing translational clinical trials aimed at biomarker discovery will help identify, which breast cancer patients are most likely to benefit from adjuvant statin therapy, and will add valuable clinical knowledge to the field. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

ERICA: prevalence of dyslipidemia in Brazilian adolescents

PubMed Central

Faria, José Rocha; Bento, Vivian Freitas Rezende; Baena, Cristina Pellegrino; Olandoski, Marcia; Gonçalves, Luis Gonzaga de Oliveira; Abreu, Gabriela de Azevedo; Kuschnir, Maria Cristina Caetano; Bloch, Katia Vergetti

2016-01-01

ABSTRACT OBJECTIVE To determine the distribution of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in Brazilian adolescents, as well as the prevalence of altered levels of such parameters. METHODS Data from the Study of Cardiovascular Risks in Adolescents (ERICA) were used. This is a country-wide, school-based cross-sectional study that evaluated 12 to 17-year old adolescents living in cities with over 100,000 inhabitants. The average and distribution of plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were evaluated. Dyslipidemia was determined by levels of total cholesterol ≥ 170 mg/dl, LDL cholesterol ≥ 130 mg/dl, HDL cholesterol < 45 mg/dL, or triglycerides ≥ 130 mg/dl. The data were analyzed by gender, age, and regions in Brazil. RESULTS We evaluated 38,069 adolescents – 59.9% of females, and 54.2% between 15 and 17 years. The average values found were: total cholesterol = 148.1 mg/dl (95%CI 147.1-149.1), HDL cholesterol = 47.3 mg/dl (95%CI 46.7-47.9), LDL cholesterol = 85.3 mg/dl (95%CI 84.5-86.1), and triglycerides = 77.8 mg/dl (95%CI 76.5-79.2). The female adolescents had higher average levels of total cholesterol, LDL cholesterol, and HDL cholesterol, without differences in the levels of triglycerides. We did not observe any significant differences between the average values among 12 to 14 and 15- to 17-year old adolescents. The most prevalent lipid alterations were low HDL cholesterol (46.8% [95%CI 44.8-48.9]), hypercholesterolemia (20.1% [95%CI 19.0-21.3]), and hypertriglyceridemia (7.8% [95%CI 7.1-8.6]). High LDL cholesterol was found in 3.5% (95%CI 3.2-4.0) of the adolescents. Prevalence of low HDL cholesterol was higher in Brazil’s North and Northeast regions. CONCLUSIONS A significant proportion of Brazilian adolescents has alterations in their plasma lipids. The high prevalence of low HDL cholesterol and hypertriglyceridemia, especially in Brazil’s North and Northeast regions, must be analyzed in future studies, to support the creation of strategies for efficient interventions. PMID:26910544

Effects of dietary cholesterol supplementation on growth and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with cottonseed meal or rapeseed meal.

PubMed

Deng, Junming; Zhang, Xi; Long, Xiaowen; Tao, Linli; Wang, Zhen; Niu, Guoyi; Kang, Bin

2014-12-01

This study was conducted to evaluate the effects of cholesterol on growth and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with cottonseed meal (CSM) or rapeseed meal (RSM). Four experimental diets were formulated to contain 550 g kg(-1) CSM or 450 g kg(-1) RSM with or without 9 g kg(-1) supplemental cholesterol. Growth rate and feed utilization efficiency of fish fed diets with 450 g kg(-1) RSM were inferior to fish fed diets with 550 g kg(-1) CSM regardless of cholesterol level. Dietary cholesterol supplementation increased the growth rate of fish fed diets with RSM, and growth rate and feed utilization efficiency of fish fed diets with CSM. Similarly, dietary cholesterol supplementation increased the plasma total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triiodothyronine levels, but decreased the plasma triglycerides and cortisol levels of fish fed diets with RSM or CSM. In addition, supplemental cholesterol increased the free cholesterol and TC levels in intestinal contents, but decreased the hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase activity of fish fed diets with RSM or CSM. These results indicate that 9 g kg(-1) cholesterol supplementation seems to improve the growth of rainbow trout fed diets with CSM or RSM, and the growth-promoting action may be related to the alleviation of the negative effects caused by antinutritional factors and/or make up for the deficiency of endogenous cholesterol in rainbow trout.

Effect of Powder Leaf Breadfruit Disposals (Arthocarpus Altilis) in Oil Mandar District and Polman Against Cholesterol and Glucose Mice (Mus Musculus)

NASA Astrophysics Data System (ADS)

Mu'nisa, A.; Asmawati, A.; Farida, A.; FA, Fressy; Erni

2018-01-01

The purpose of this study was to determine the effect of powdered leaves of breadfruit (Arthocarpus altilis) on oil is mandated origin of the Polman glucose and cholesterol levels in mice (Mus musculus). This study comprised 4 treatments and each treatment consisted of 5 replicates, ie groups of mice were fed a standard (negative control); 2 groups: group of mice fed with standard and cholesterol feed (positive control); Group 3 that mice fed with standard and Selayar oil; and group 4: group of mice fed with standard and Mandar oil that has been given powdered leaves of breadfruit. Measurement of glucose and blood cholesterol levels in mice done 3 times ie 2 weeks after the adaptation period (phase 1), 2 weeks after administration of the oil (phase 2) and 2 weeks after feeding cholesterol (stage 3). Based on the analysis of data both cholesterol and glucose levels showed that in a group of 4 decreased glucose and cholesterol levels in stage 2 but at stage 3 an increase in the group of mice given only the oil while in the group of mice given the oil and powdered leaves of breadfruit indicate glucose levels and normal cholesterol. The conclusion of this study show that the addition of powdered leaves of breadfruit into cooking oil Mandar influential in glucose levels and normalize blood cholesterol levels in mice.

Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

NASA Astrophysics Data System (ADS)

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.

The HALT Polycystic Kidney Disease Trials: Design and Implementation

PubMed Central

Torres, Vicente E.; Perrone, Ronald D.; Steinman, Theodore I.; Bae, Kyongtae T.; Miller, J. Philip; Miskulin, Dana C.; Oskoui, Frederic Rahbari; Masoumi, Amirali; Hogan, Marie C.; Winklhofer, Franz T.; Braun, William; Thompson, Paul A.; Meyers, Catherine M.; Kelleher, Cass; Schrier, Robert W.

2010-01-01

Background and objectives: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m2 were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. Results: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. Conclusions: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD. PMID:20089507

Knee osteoarthritis, dyslipidemia syndrome and exercise.

PubMed

Păstrăiguş, Carmen; Ancuţa, Codrina; Miu, Smaranda; Ancuţa, E; Chirieac, Rodica

2012-01-01

The aim of our study was to evaluate the influence of aerobic training on the dyslipedemia in patients with knee osteoarthritis (KOA). Prospective observational six-month study performed on 40 patients with KOA, fulfilling the inclusion criteria, classified according to their participation in specific aerobic training program (30 minutes/day, 5 days/ week) in two subgroups. A standard evaluation protocol was followed assessing lipid parameters (total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol levels) at baseline, three and six months. Statistical analysis was performed in SPSS 16.0, p < 0.05. Subgroup analysis has demonstrated a statistical significant improvement in plasma lipids levels in all patients performing regular aerobic training (cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol) (p < 0.05). Although the difference reported for total cholesterol, triglycerides and LDL-cholesterol after six months between subgroups was not significant (p > 0.05), the mean level of HDL-cholesterol was significantly higher in patients performing aerobic training, reaching the cardio-vascular protective levels. Regular aerobic exercise has a positive effect on plasma lipoprotein concentrations; further research is needed for the assessment of long-term effects of physical exercises for both KOA and lipid pattern.

Association of lifestyle with serum lipid levels: a study of middle-aged Japanese men.

PubMed

Nakanishi, N; Tatara, K; Nakamura, K; Suzuki, K

2000-07-01

Cross-sectional associations between lifestyle and serum lipid levels were examined in 1591 Japanese male office workers aged 35 to 59 years in Osaka, Japan. From multiple linear regression analyses, significant correlates with low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and Log triglyceride levels and the ratio of LDL cholesterol to HDL cholesterol were, in the order of relative importance: BMI, alcohol intake (negative) and age for LDL cholesterol level; BMI (negative), cigarette smoking (negative), alcohol intake, consideration for nutritional balance, hours of brisk walking, hours of walking at an ordinary pace and physical exercise for HDL cholesterol level; BMI, cigarette smoking, consideration for nutritional balance (negative), hours of work (negative), alcohol intake and coffee drinking (negative) for Log triglyceride level; and BMI, alcohol intake (negative), cigarette smoking, consideration for nutritional balance (negative), age, hours of brisk walking (negative) and the frequency of snack intake between meals for the ratio of LDL cholesterol to HDL cholesterol. Our data suggest that obesity, cigarette smoking and snack intake between meals are atherogenic whereas alcohol consumption, consideration for nutritional balance and walking long hours, especially at a brisk pace, are anti-atherogenic in middle-aged Japanese men.

[Hypercholesterolemia: a therapeutic approach].

PubMed

Moráis López, A; Lama More, R A; Dalmau Serra, J

2009-05-01

High blood cholesterol levels represent an important cardiovascular risk factor. Hypercholesterolemia is defined as levels of total cholesterol and low-density lipoprotein cholesterol above 95th percentile for age and gender. For the paediatric population, selective screening is recommended in children older than 2 years who are overweight, with a family history of early cardiovascular disease or whose parents have high cholesterol levels. Initial therapeutic approach includes diet therapy, appropriate physical activity and healthy lifestyle changes. Drug treatment should be considered in children from the age of 10 who, after having followed appropriate diet recommendations, still have very high LDL-cholesterol levels or moderately high levels with concomitant risk factors. In case of extremely high LDL-cholesterol levels, drug treatment should be taken into consideration at earlier ages (8 years old). Modest response is usually observed with bile acid-binding resins. Statins can be considered first-choice drugs, once evidence on their efficacy and safety has been shown.

Hypercholesterolemia Induces Angiogenesis and Accelerates Growth of Breast Tumors in Vivo

PubMed Central

Pelton, Kristine; Coticchia, Christine M.; Curatolo, Adam S.; Schaffner, Carl P.; Zurakowski, David; Solomon, Keith R.; Moses, Marsha A.

2015-01-01

Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo. PMID:24952430

The Effects of Altered Membrane Cholesterol Levels on Sodium Pump Activity in Subclinical Hypothyroidism.

PubMed

Roy, Suparna; Dasgupta, Anindya

2017-03-01

Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na⁺/K⁺-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients. In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T₄) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis. Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T₄ levels. No dependence on serum cholesterol was observed in either case. Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations. Copyright © 2017 Korean Endocrine Society

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

PubMed

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

2016-08-01

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 investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed Central

Schonewille, Marleen; Freark de Boer, Jan; 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 investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. PMID:27313057

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

PubMed Central

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

Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat diets.

PubMed

Cha, Jae Hoon; Kim, Sun Rim; Kang, Hyun Joong; Kim, Myung Hwan; Ha, Ae Wha; Kim, Woo Kyoung

2016-10-01

Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily. Serum and hepatic levels of total lipids, triglycerides, and total cholesterol as well as serum free fatty acid, glucose, and insulin levels were determined. The mRNA expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7-alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and tumor necrosis factor α were determined. Oral administration of CS extract with HF improved serum glucose and insulin levels as well as attenuated HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT, and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and HFCS group were not statistically different. CS extract supplementation with a high-fat diet improves levels of adipocytokine secretion and glucose homeostasis. CS extract is also effective in decreasing the regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic levels of cholesterol though modulation of mRNA expression levels of HMG-CoA reductase, ACAT, and FXR.

[Study on the dynamic variations and influencing factors of serum lipid levels during pregnancy and postpartum].

PubMed

Xu, D; Liang, C; Chen, L; Wu, X D; He, J

2018-04-25

Objective: To study the variations and influencing factors of serum triglycerides and cholesterol levels during pregnancy and postpartum. Methods: A retrospective study was performed among 5 020 healthy singleton (95.10%, 4 774/5 020) and twin (4.90%, 246/5 020) women who had delivery in Women's Hospital, Zhejiang University School of Medicine from January 2011 to December 2016. Serum triglycerides and cholesterol levels during pregnancy and postpartum of all the cases were collected. Both singleton and twin pregnant women were divided into advanced age and appropriate age groups, and then data of serum sample were assigned to 3 groups according to the gestation weeks, which were second trimester pregnancy (24-28 gestation weeks) , third trimester pregnancy (32-41 gestation weeks) and postpartum (within 72 hours after delivery) . The serum triglycerides and cholesterol levels in each groups were compared. Results: (1) Serum triglycerides and cholesterol levels during the second trimester pregnancy, third trimester pregnancy and postpartum were higher than levels of non-pregnancy in both singleton and twin groups (all P< 0.05) . (2) Serum triglycerides and cholesterol levels in the third trimester pregnancy group were higher than those of second trimester pregnancy group in both advanced age and appropriate aged women regardless singleton or twin pregnancy (all P< 0.05) . The 95% CI of serum lipid levels in each group during second and third trimester pregnancy were as follows: in appropriate aged singleton group, the triglycerides levels were 1.07-4.13 and 1.52-7.21 mmol/L, and the cholesterol levels were 2.77-12.11 and 4.44-9.36 mmol/L. In advanced aged singleton group, the triglycerides levels were 1.28-4.61 and 1.70-7.80 mmol/L, and the cholesterol levels were 4.35-8.40 and 4.46-9.35 mmol/L; in appropriate aged twin group, the triglycerides levels were 1.39-7.16 and 1.90-9.29 mmol/L, and the cholesterol levels were 4.99-12.16 and 4.52-10.07 mmol/L; in advanced aged twin group, the triglycerides levels were 1.61-5.32 and 1.94-9.29 mmol/L, and the cholesterol levels were 5.24-8.10 and 4.53-8.86 mmol/L. (3) Serum lipids levels rapidly decreased during postpartum compared to the third trimester pregnancy. The 95% CI of blood lipid levels in each group were as follows: in appropriate aged singleton group, the triglycerides level was 0.90-5.64 mmol/L and the cholesterol level was 4.70-8.52 mmol/L; in advanced aged singleton group, the triglycerides level was 0.87-5.43 mmol/L and the cholesterol level was 4.68-9.04 mmol/L; in appropriate aged twin group, the triglycerides level was 1.20-8.21 mmol/L and the cholesterol level was 4.66-8.45 mmol/L; in advanced aged twin group, the triglycerides level was 1.32-6.61 mmol/L, and the cholesterol level was 5.01-7.94 mmol/L. (4) Serum triglycerides and cholesterol levels in twin pregnant women were significantly higher than in singleton during the second trimester and third trimester pregnancy both in advanced age and appropriate age groups (all P< 0.05) . During postpartum, there was no difference in serum lipid levels between the singleton and twin pregnant women in appropriate age group (triglycerides: P= 0.982; cholesterol: P= 0.759, respectively) . While the serum lipid levels in twin pregnant women were significantly higher than those of singleton women in advanced age group (triglycerides: P= 0.000; cholesterol: P= 0.000, respectively) . Conclusions: The standard of serum lipid levels of non-pregnant adults is not suitable for assessing that in pregnant women. Regardless of singleton or twin pregnancy, serum triglyceride and cholesterol levels during pregnancy elevate with the increasing gestational week and then rapidly decrease during postpartum. Age and twins are the influencing factors of the elevated physiological lipid levels during pregnancy.

High plasma level of remnant-like particle cholesterol in the metabolic syndrome.

PubMed

Satoh, Akira; Adachi, Hisashi; Tsuruta, Makoto; Hirai, Yuji; Hiratsuka, Akiko; Enomoto, Mika; Furuki, Kumiko; Hino, Asuka; Takeuchi, Tomohiro; Imaizumi, Tsutomu

2005-10-01

The metabolic syndrome is associated with a high incidence of cardiovascular disease even when the abnormalities present in the syndrome are mild. The underlying mechanism of the metabolic syndrome has not been elucidated. We investigated whether a strong atherogenic lipoprotein, remnant-like particle (RLP) lipoprotein cholesterol, is elevated in the metabolic syndrome. We performed a health examination among the residents of a rural community in Japan. Complete datasets, including fasting RLP cholesterol levels, were obtained in 1,261 subjects (509 men and 752 women) without diabetes and who were not taking lipid-lowering drugs. The subjects' medical history, use of alcohol, and smoking habits were ascertained by a questionnaire. All of the components of the metabolic syndrome were significantly related to RLP cholesterol by univariate analysis. Total cholesterol and smoking habits were also positively associated with RLP cholesterol. The subjects with the metabolic syndrome showed only mild abnormalities of each component. When RLP cholesterol levels were stratified by the number of the components of the metabolic syndrome, there was a strong association between RLP cholesterol levels and the number of components (P < 0.001 and F = 72.7). RLP cholesterol levels are elevated in the metabolic syndrome, and this elevation may underlie the high incidence of cardiovascular disease in the metabolic syndrome.

Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-09-01

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.

Pitfalls in the detection of cholesterol in Huntington's disease models.

PubMed

Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

2012-10-11

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

Disparities in Intratumoral Steroidogenesis

DTIC Science & Technology

2014-07-01

shown), but does raise cholesterol levels significantly(18-22) (Fig 5). The diets are used with and without ezetimibe , a cholesterol reducing drug...yielding 4 base diet groups: 1) LFNC; 2) LFNC + ezetimibe (30 mg/kg/day); 3) HFHC; and 4) HFHC + ezetimibe (30 mg/kg/day). Critical comments...Serum Cholesterol Levels. Mice were fed either high fat, high cholesterol (HFHC) or a low fat, no cholesterol (LFNC) diet ± ezetimibe (Z) and bled

Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men

PubMed Central

Cederberg, Henna; Gylling, Helena; Miettinen, Tatu A.; Paananen, Jussi; Vangipurapu, Jagadish; Pihlajamäki, Jussi; Kuulasmaa, Teemu; Stančáková, Alena; Smith, Ulf; Kuusisto, Johanna; Laakso, Markku

2013-01-01

We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes. PMID:23840693

Antilithiasic and Hypolipidaemic Effects of Raphanus sativus L. var. niger on Mice Fed with a Lithogenic Diet

PubMed Central

Castro-Torres, Ibrahim Guillermo; Naranjo-Rodríguez, Elia Brosla; Domínguez-Ortíz, Miguel Ángel; Gallegos-Estudillo, Janeth; Saavedra-Vélez, Margarita Virginia

2012-01-01

In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine. PMID:23093836

Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo.

PubMed

Pelton, Kristine; Coticchia, Christine M; Curatolo, Adam S; Schaffner, Carl P; Zurakowski, David; Solomon, Keith R; Moses, Marsha A

2014-07-01

Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, C.H.; Chen, S.M.; Ogle, C.W.

1989-01-01

The effects of short-term treatment with orally-administered zinc sulfate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulfate for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free {beta}-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free {beta}-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol inmore » the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulfate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free {beta}-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.« less

Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.

PubMed

Vega, Gloria Lena; Weiner, Myron F; Lipton, Anne M; Von Bergmann, Klaus; Lutjohann, Dieter; Moore, Carol; Svetlik, Doris

2003-04-01

The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in beta-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.

Exchanging partially hydrogenated fat for palmitic acid in the diet increases LDL-cholesterol and endogenous cholesterol synthesis in normocholesterolemic women.

PubMed

Sundram, Kalyana; French, Margaret A; Clandinin, M Thomas

2003-08-01

Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations. Hydrogenated fats containing trans fatty acids increase plasma total cholesterol (TC) and LDL-cholesterol while depressing HDL-cholesterol levels. Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately. Thus, it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol. Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30% of energy as fat for a fourweek period. One diet was high in palmitic acid (10.6% of energy) from palm olein and the other diet exchanged 5.6% of energy as partially hydrogenated fat for palmitic acid. This fat blend resulted in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7%. The hydrogenated fat diet treatment provided 3.1% of energy as elaidic acid. For each dietary treatment, the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood samples were obtained for blood lipid and lipoprotein measurements. Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level. Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol. Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol.

Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson's disease.

PubMed

Roy, Avik; Ghosh, Anamitra; Jana, Arundhati; Liu, Xiaojuan; Brahmachari, Saurav; Gendelman, Howard E; Pahan, Kalipada

2012-01-01

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac), but not p21(ras), attenuated the production of ROS from activated microglia. Inhibition of both p21(ras) and p21(rac) activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras) and p21(rac)in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras) and p21(rac), protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.

Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease

PubMed Central

Jana, Arundhati; Liu, Xiaojuan; Brahmachari, Saurav; Gendelman, Howard E.; Pahan, Kalipada

2012-01-01

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21rac, but not p21ras, attenuated the production of ROS from activated microglia. Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21ras and p21rac in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Oral administration of NaPB reduced nigral activation of p21ras and p21rac, protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders. PMID:22723850

The Canadian experience: why Canada decided against an upper limit for cholesterol.

PubMed

McDonald, Bruce E

2004-12-01

Canada, like the United States, held a "consensus conference on cholesterol" in 1988. Although the final report of the consensus panel recommended that total dietary fat not exceed 30 percent and saturated fat not exceed 10 percent of total energy intake, it did not specify an upper limit for dietary cholesterol. Similarly, the 1990, Health Canada publication "Nutrition Recommendations: The Report of the Scientific Review Committee" specified upper limits for total and saturated fat in the diet but did not specify an upper limit for cholesterol. Canada's Guidelines for Healthy Eating, a companion publication from Health Canada, suggested that Canadians "choose low-fat dairy products, lean meats, and foods prepared with little or no fat" while enjoying "a variety of foods." Many factors contributed to this position but a primary element was the belief that total dietary fat and saturated fat were primary dietary determinants of serum total and low-density lipoprotein (LDL) cholesterol levels, not dietary cholesterol. Hence, Canadian health authorities focused on reducing saturated fat and trans fats in the Canadian diet to help lower blood cholesterol levels rather than focusing on limiting dietary cholesterol. In an effort to allay consumer concern with the premise that blood cholesterol level is linked to dietary cholesterol, organizations such as the Canadian Egg Marketing Agency (CEMA) reminded health professionals, including registered dietitians, family physicians and nutrition educators, of the extensive data showing that there is little relationship between dietary cholesterol intake and cardiovascular mortality. In addition, it was pointed out that for most healthy individuals, endogenous synthesis of cholesterol by the liver adjusts to the level of dietary cholesterol intake. Educating health professionals about the relatively weak association between dietary cholesterol and the relatively strong association between serum cholesterol and saturated fat and trans fats helped keep consumers informed about healthy diets and ways to control blood cholesterol.

Cholesterol Level: Can It Be Too Low?

MedlinePlus

... total cholesterol level has been associated with some health problems. Doctors are still trying to find out more about the connection between low cholesterol and health risks. There is no consensus on how to ...

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

PubMed

Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Pharmacological activation of LXRs decreases amyloid-β levels in Niemann-Pick type C model cells.

PubMed

Stefulj, Jasminka; Peric, Maja; Malnar, Martina; Kosicek, Marko; Schweinzer, Cornelia; Zivkovic, Jelena; Scholler, Monika; Panzenboeck, Ute; Hecimovic, Silva

2013-01-01

Niemann-Pick type C disease (NPC) is an inherited disorder mainly caused by loss-of-function mutations in the NPC1 gene, that lead to intracellular cholesterol accumulation and disturbed cholesterol homeostasis. Similarly to Alzheimer's disease (AD), NPC is associated with progressive neurodegeneration and altered metabolism of amyloid precursor protein (APP). Liver X receptors (LXRs), the key transcriptional regulators of cholesterol homeostasis, were reported to play neuroprotective roles in NPC mice. We investigated the impacts of LXRs on APP metabolism in mutant CHO cells lacking the NPC1 gene (-NPC1 cells). Pharmacological activation of LXRs in -NPC1 cells tended to reduce the ratio of total secreted APP (sAPP) to full length APP (flAPP) levels and sAPPβ levels as well as to increase the ratio of APP Cterminal fragments to flAPP levels, resulting in decreased levels of amyloid β (Aβ) peptides. -NPC1 cells treated with LXR agonist TO901317 (TO90) displayed a modest increase in cholesterol efflux to apolipoprotein A-I (apoA-I) but not to HDL3, or in the absence of extracellular cholesterol acceptors. The observed similar reduction of Aβ levels upon TO90 treatment in the presence or in the absence of extracellular apoA-I indicated a cholesterol-efflux independent effect of TO90 on Aβ levels. Furthermore, TO90 had no effect on the cholesterol synthesis rate in -NPC1 cells, while it reduced the rate of cholesterol esterification. The obtained results indicate that LXR activation may decrease Aβ levels in NPC1- deficient conditions. The underlying mechanism of this action does not appear to be related to effects on cholesterol efflux or synthesis rates.

Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats.

PubMed

Lapphanichayakool, Phakhamon; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip

2017-01-01

The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called "sericin-derived oligopeptides" (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg -1  day -1 , 50 mg kg -1  day -1 , and 200 mg kg -1  day -1 ) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet. Triglyceride and HDL-cholesterol levels were not significantly changed among all groups. The fecal contents of bile acids and cholesterol did not differ among high-cholesterol fed rats. SDO dose-dependently reduced cholesterol solubility in lipid micelles, and inhibited cholesterol uptake in monolayer Caco-2 cells. SDO also effectively bound to all three types of bile salts including taurocholate, deoxytaurocholate, and glycodeoxycholate. Direct interaction with bile acids of SDO may disrupt micellar cholesterol solubility, and subsequently reduce the absorption of dietary cholesterol in intestines. Taking all data together, SDO or sericin peptides exhibit a beneficial effect on blood cholesterol levels and could be potentially used as a health-promoting dietary supplement or nutraceutical product.

Serum Lipid Levels in Patients with Eating Disorders.

PubMed

Nakai, Yoshikatsu; Noma, Shun'ichi; Fukusima, Mitsuo; Taniguchi, Ataru; Teramukai, Satoshi

2016-01-01

Objective To evaluate some risk factors for cardiovascular diseases in feeding and eating disorders, the degree of lipid abnormalities was investigated in a large Japanese cohort of different groups of feeding and eating disorders, according to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012). Methods Participants in the current study included 732 women divided into four groups of feeding and eating disorders: anorexia nervosa, restricting type (AN-R); anorexia nervosa, binge-eating/purging type; bulimia nervosa (BN); and binge-eating disorder (BED). We measured the serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride in these participants. Low-density-lipoprotein (LDL) cholesterol and non-HDL cholesterol levels were also calculated. Results The concentrations of LDL cholesterol and non-HDL cholesterol were widely distributed in all groups. When the LDL cholesterol risk was defined as ≥120 mg/dL and the non-HDL cholesterol risk as ≥150 mg/dL, according to the JAS Guidelines 2012, the proportion of LDL cholesterol risk ranged from 29.6% (BN) to 38.6% (AN-R), and the proportion of non-HDL cholesterol risk ranged from 17.8% (BN) to 30.1% (BED). Conclusion The present findings suggest the existence of LDL cholesterol risk and non-HDL cholesterol risk in all groups of eating disorders. Given the chronicity of this condition, the development of elevated concentrations of LDL cholesterol and non-HDL cholesterol at an early age may increase the risk of cardiovascular diseases.

Serum Cholesterol Levels in College Students: Opportunities for Education and Intervention.

ERIC Educational Resources Information Center

Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.

1999-01-01

Analyzed lipid profiles in 1,088 college students at a university where lipid profiles were available to students in selected health/wellness courses. Mean total cholesterol levels were similar for men and women, but men had significantly lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol than women. About 11…

Pitfalls in the detection of cholesterol in Huntington’s disease models

PubMed Central

Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

2012-01-01

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington’s disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it PMID:23145355

Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer's Disease.

PubMed

Pan, Yongming; Xu, Jianqin; Chen, Cheng; Chen, Fangming; Jin, Ping; Zhu, Keyan; Hu, Chenyue W; You, Mengmeng; Chen, Minli; Hu, Fuliang

2018-01-01

Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

PubMed

Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

The association of very-low-density lipoprotein with ankle-brachial index in peritoneal dialysis patients with controlled serum low-density lipoprotein cholesterol level

PubMed Central

2013-01-01

Background Peripheral artery disease (PAD) represents atherosclerotic disease and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to show an atherogenic lipid profile. In this study, we investigated the relationship between lipid profile and ankle-brachial index (ABI) as an index of atherosclerosis in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level. Methods Thirty-five PD patients, whose serum LDL cholesterol level was controlled at less than 120mg/dl, were enrolled in this cross-sectional study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the mean size of lipoprotein particles were measured using an improved method, namely, high-performance gel permeation chromatography. Multivariate linear regression analysis was adjusted for diabetes mellitus and cardiovascular and/or cerebrovascular diseases. Results The mean (standard deviation) age was 61.6 (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or lower) was observed in 7 patients (low-ABI group). The low-ABI group showed significantly higher cholesterol proportions in the chylomicron fraction and large very-low-density lipoproteins (VLDLs) (Fractions 3–5) than the high-ABI group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI was negatively associated with serum VLDL cholesterol level (parameter estimate=-0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4, parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62, p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and the size of VLDL particles (parameter estimate=-0.0352, p=0.032). Conclusions This study showed that the characteristics of VLDL particles were associated with ABI among PD patients. Lowering serum VLDL level may be an effective therapy against atherosclerosis in PD patients after the control of serum LDL cholesterol level. PMID:24093487

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

PubMed

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. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors.

PubMed

Kovanen, P T

1987-02-01

The endogenous lipoprotein system (very low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL] cascade) holds the key to understanding the mechanisms by which hormones, diet, and drugs interact to regulate the plasma cholesterol level. Crucial components of this system are hepatic LDL receptors that mediate the uptake and degradation of plasma LDL. With experimental animals, it has been possible to demonstrate that hepatic LDL receptors are sensitive to hormonal, dietary, and pharmacologic manipulation. The decrease in number of hepatic LDL receptors in hypothyroidism or after cholesterol feeding leads to elevation of plasma LDL cholesterol levels. Conversely, the increase in number of hepatic LDL receptors results in lowering of plasma LDL cholesterol levels. This can be observed in hyperthyroidism, during administration of pharmacologic doses of 17 alpha-ethinyl estradiol, or during treatment with cholesterol-lowering drugs such as the bile acid-binding resins and cholesterol-synthesis inhibitors. Since cholesterol excretion from the body occurs via the liver, the increased efficiency of disposal of plasma cholesterol by increasing hepatic LDL receptors will ultimately lead to depletion of excessive body cholesterol. Pharmacologic regulation of hepatic LDL receptors should be a valuable tool in the prevention and therapy of atherosclerosis.

Cholesterol metabolism and transport in the pathogenesis of Alzheimer's disease.

PubMed

Martins, Ian J; Berger, Tamar; Sharman, Matthew J; Verdile, Giuseppe; Fuller, Stephanie J; Martins, Ralph N

2009-12-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.

Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.

PubMed Central

Cohen, R D; Castellani, L W; Qiao, J H; Van Lenten, B J; Lusis, A J; Reue, K

1997-01-01

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL. PMID:9109435

Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats.

PubMed

Aizawa, Koichi; Inakuma, Takahiro

2009-12-01

The effects of dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), on lipid metabolism were examined. Young male Wistar rats were fed diets containing paprika powder, paprika organic solvent extract, residue of paprika extract, and purified capsanthin. Administration of purified capsanthin for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P < 0.05) without detectable differences in plasma total cholesterol and TAG concentrations. A statistically significant correlation (r 0.567; P < 0.001) was found between dietary capsanthin concentrations and plasma HDL-cholesterol concentrations. Animals receiving diets containing two different capsanthin concentrations exhibited dose-dependent increases in plasma HDL-cholesterol (r 0.597; P < 0.005). While capsanthin was absent in the liver of animals fed the basal diet, it increased markedly in capsanthin-fed animals (P < 0.001). Quantitative analyses of hepatic mRNA levels revealed that capsanthin administration resulted in up-regulation of mRNA for apoA5 and lecithin cholesterol acyltransferase (LCAT), without significant differences in other mRNA levels related to HDL-cholesterol metabolism. These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity.

High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides.

PubMed

Uehara, Yoshinari; Chiesa, Giulia; Saku, Keijiro

2015-01-01

Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.

Results of a heart disease risk-factor screening among traditional college students.

PubMed

Spencer, Leslie

2002-05-01

The author collected data on serum cholesterol, blood pressure, and self-reported health behavior in 226 college students aged 18 to 26 years. Twenty-nine percent had undesirable total cholesterol levels, 10% had high cholesterol, 10% had high systolic blood pressure, and 11% had high diastolic blood pressure. Half or more of the participants consumed a diet high in saturated fats, engaged in binge drinking, had a parental risk for high cholesterol or blood pressure, or reported they experienced elevated stress levels. Men had higher risk-factor levels than women. Findings from a regression analysis revealed that smoking, binge drinking, lack of cardiovascular exercise, and eating a high saturated-fat diet were predictive of undesirable cholesterol levels. Study limitations included self-selection of participants and single measurements of blood pressure and cholesterol. Trained students served as screeners in the program for providing an effective, low-cost screening intervention.

Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance

PubMed Central

Barrientos, G.; Sánchez-Aguilera, P.; Jaimovich, E.; Hidalgo, C.

2017-01-01

Membrane cholesterol is critical for signaling processes in a variety of tissues. We will address here current evidence supporting an emerging role of cholesterol on excitation-contraction coupling and glucose transport in skeletal muscle. We have centered our review on the transverse tubule system, a complex network of narrow plasma membrane invaginations that propagate membrane depolarization into the fiber interior and allow nutrient delivery into the fibers. We will discuss current evidence showing that transverse tubule membranes have remarkably high cholesterol levels and we will address how modifications of cholesterol content influence excitation-contraction coupling. In addition, we will discuss how membrane cholesterol levels affect glucose transport by modulating the insertion into the membrane of the main insulin-sensitive glucose transporter GLUT4. Finally, we will address how the increased membrane cholesterol levels displayed by obese animals, which also present insulin resistance, affect these two particular skeletal muscle functions. PMID:28367451

Diphenyl diselenide decreases serum levels of total cholesterol and tissue oxidative stress in cholesterol-fed rabbits.

PubMed

de Bem, Andreza Fabro; Portella, Rafael de Lima; Colpo, Elisângela; Duarte, Marta Maria Medeiros Frescura; Frediane, Andressa; Taube, Paulo Sergio; Nogueira, Cristina Wayne; Farina, Marcelo; da Silva, Edson Luiz; Teixeira Rocha, João Batista

2009-07-01

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.

PubMed

Sandhya, V G; Rajamohan, T

2006-01-01

The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.

Excess dietary cholesterol may have an adverse effect on growth performance of early post-larval Litopenaeus vannamei

PubMed Central

2012-01-01

One experiment was conducted to determine the nutritive value of cholesterol for post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0, 0.5%, 1% and 2% cholesterol, respectively) were fed to triplicate groups of L. vannamei shrimp (mean initial wet weight 0.8 mg) for 27 days. After the trial, shrimp fed the D1 diet had the best growth performance (final body weights: FBW; weight gain: WG; specific growth rate: SGR), while there was no significant difference between diet treatments with respect to survival. The whole body crude protein level in the shrimp decreased with the increase in dietary cholesterol levels, while the whole body crude lipid level in shrimps in the D4 diet treatment was significantly higher (P < 0.05) than in other diet treatments. Dietary analysis indicated that the D1 diet contained 0.92% cholesterol prior to supplementation, which may have satisfied the dietary cholesterol requirement of post-larval L. vannamei; excess dietary cholesterol may thus lead to adverse effects on the growth performance of post-larval shrimp. PMID:22958647

Trends in lipid profiles and descriptive characteristics of U.S. adults with and without diabetes and cholesterol-lowering medication use-National Health and Nutrition Examination Survey, 2003-2012, United States.

PubMed

Mercado, Carla I; Gregg, Edward; Gillespie, Cathleen; Loustalot, Fleetwood

2018-01-01

With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes. Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication. Population number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003-2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity. Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 --3.5), LDL-c = -8.0% (-10.4 --5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 --5.7); LDL-c = -13.7% (-17.1 --10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 --1.6); LDL-c = -4.3% (-7.1 --1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003-2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications. Diabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management.

Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin

PubMed Central

Chakrabarti, Rima S; Ingham, Sally A; Kozlitina, Julia; Gay, Austin; Cohen, Jonathan C; Radhakrishnan, Arun; Hobbs, Helen H

2017-01-01

Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans. DOI: http://dx.doi.org/10.7554/eLife.23355.001 PMID:28169829

Advance, Retreat, and Halt of Abrupt Gravel-Sand Transitions in Alluvial Rivers

NASA Astrophysics Data System (ADS)

Blom, Astrid; Chavarrías, Víctor; Ferguson, Robert I.; Viparelli, Enrica

2017-10-01

Downstream fining of bed sediment in alluvial rivers is usually gradual, but often an abrupt decrease in characteristic grain size occurs from about 10 to 1 mm, i.e., a gravel-sand transition (GST) or gravel front. Here we present an analytical model of GST migration that explicitly accounts for gravel and sand transport and deposition in the gravel reach, sea level change, subsidence, and delta progradation. The model shows that even a limited gravel supply to a sand bed reach induces progradation of a gravel wedge and predicts the circumstances required for the gravel front to advance, retreat, and halt. Predicted modern GST migration rates agree well with measured data at Allt Dubhaig and the Fraser River, and the model qualitatively captures the behavior of other documented gravel fronts. The analysis shows that sea level change, subsidence, and delta progradation have a significant impact on the GST position in lowland rivers.

Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study.

PubMed

Olsen, Tom Skyhøj; Christensen, Rune Haubo Bojesen; Kammersgaard, Lars Peter; Andersen, Klaus Kaae

2007-10-01

Evidence of a causal relation between serum cholesterol and stroke is inconsistent. We investigated the relation between total serum cholesterol and both stroke severity and poststroke mortality to test the hypothesis that hypercholesterolemia is primarily associated with minor stroke. In the study, 652 unselected patients with ischemic stroke arrived at the hospital within 24 hours of stroke onset. A measure of total serum cholesterol was obtained in 513 (79%) within the 24-hour time window. Stroke severity was measured with the Scandinavian Stroke Scale (0=worst, 58=best); a full cardiovascular risk profile was established for all. Death within 10 years after stroke onset was obtained from the Danish Registry of Persons. Mean+/-SD age of the 513 patients was 75+/-10 years, 54% were women, and the mean+/-SD Scandinavian Stroke Scale score was 39+/-17. Serum cholesterol was inversely and almost linearly related to stroke severity: an increase of 1 mmol/L in total serum cholesterol resulted in an increase in the Scandinavian Stroke Scale score of 1.32 (95% CI, 0.28 to 2.36, P=0.013), meaning that higher cholesterol levels are associated with less severe strokes. A survival analysis revealed an inverse linear relation between serum cholesterol and mortality, meaning that an increase of 1 mmol/L in cholesterol results in a hazard ratio of 0.89 (95% CI, 0.82 to 0.97, P=0.01). The results of our study support the hypothesis that a higher cholesterol level favors development of minor strokes. Because of selection, therefore, major strokes are more often seen in patients with lower cholesterol levels. Poststroke mortality, therefore, is inversely related to cholesterol.

Probiotic Properties of Lactobacillus Strains Isolated from Tibetan Kefir Grains

PubMed Central

Zheng, Yongchen; Lu, Yingli; Wang, Jinfeng; Yang, Longfei; Pan, Chenyu; Huang, Ying

2013-01-01

The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB) isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH) activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD) rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05) decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05) higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05) increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05) higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for manufacturing novel fermented foods. PMID:23894554

EFFECT OF THE LEVEL AND TYPE OF DIETARY FAT ON THE METABOLISM OF CHOLESTEROL AND BETA LIPOPROTEINS IN THE CEBUS MONKEY

PubMed Central

Portman, Oscar W.; Hegsted, D. Mark; Stare, Fredrick J.; Bruno, Dorothy; Murphy, Robert; Sinisterra, Leonardo

1956-01-01

A study was carried out to determine the effect of the level and type of dietary fat on the concentration of cholesterol and beta lipoproteins in the sera of Cebus monkeys. Three groups of monkeys were fed isocaloric diets containing a fixed ratio of alpha protein and cholesterol to calories but with different amounts of corn oil and sucrose. Corn oil provided 10, 32, and 45 per cent of the calories in the three diets, and the level of sucrose was varied inversely. After 8 weeks the serum cholesterol and Sf 12 to 100 beta lipoprotein concentrations were significantly greater in the medium and high fat groups. When corn oil was decreased from 45 to 10 per cent of dietary calories and sucrose was increased, the serum cholesterol fell in all cases, and when the reverse change was made, the concentration of serum cholesterol increased. Variation in dietary sucrose had no specific effect. Substitution of starch for sucrose with diets otherwise constant did not cause significant change in the concentration of serum cholesterol. When monkeys fed corn oil diets at any of three levels were changed to hydrogenated cottonseed oil diets at the same level, the serum cholesterol and Sf 12 to 100 beta lipoproteins rose. However, hydrogenated cottonseed oil had no greater hypercholesteremic effect than did corn oil in the absence of dietary cholesterol. Diets containing lard with cholesterol also produced strikingly greater serum lipide responses than did diets based on corn oil and cholesterol. Hydrogenated cottonseed oil had a greater hypercholesteremic effect than an unhydrogenated cottonseed oil from the same lot. Preliminary studies indicated that the saturated fats (hydrogenated cottonseed oil) produced the most striking elevation of serum cholesterol values (above controls fed corn oil) when casein was the dietary protein. PMID:13376806

DIETARY FAT AND HYPERCHOLESTEREMIA IN THE CEBUS MONKEY

PubMed Central

Portman, Oscar W.; Sinisterra, Leonardo

1957-01-01

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection. After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard. Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption. PMID:13475627

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

PubMed

Pezzini, Alessandro; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, Rossella; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, Giovanni; Del Zotto, Elisabetta; Morotti, Andrea; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Bonaiti, Silvia; La Spina, Paolo; Marcello, Norina; Micieli, Giuseppe; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro

2016-09-01

Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Malnutrition-Inflammation Modifies the Relationship of Cholesterol with Cardiovascular Disease

PubMed Central

Astor, Brad C.; Greene, Tom; Erlinger, Thomas; Kusek, John W.; Lipkowitz, Michael; Lewis, Julia A.; Randall, Otelio S.; Hebert, Lee; Wright, Jackson T; Kendrick, Cynthia A.; Gassman, Jennifer; Bakris, George; Kopple, Joel D.; Appel, Lawrence J.

2010-01-01

In moderate and severe CKD, the association of cholesterol with subsequent cardiovascular disease (CVD) is weak. We examined whether malnutrition or inflammation (M-I) modifies the risk relationship between cholesterol levels and CVD events in African Americans with hypertensive CKD and a GFR between 20 and 65 ml/min per 1.73 m2. We stratified 990 participants by the presence or absence of M-I, defined as body mass index <23 kg/m2 or C-reactive protein >10 mg/L at baseline. The primary composite outcome included cardiovascular death or first hospitalization for coronary artery disease, stroke, or congestive heart failure occurring during a median follow-up of 77 months. Baseline total cholesterol (212 ± 48 versus 212 ± 44 mg/dl) and overall incidence of the primary CVD outcome (19 versus 21%) were similar in participants with (n = 304) and without (n = 686) M-I. In adjusted analyses, the CVD composite outcome exhibited a significantly stronger relationship with total cholesterol for participants without M-I than for participants with M-I at baseline (P < 0.02). In the non–M-I group, the cholesterol-adjusted hazard ratio (HR) for CVD increased progressively across cholesterol levels: HR = 1.19 [95% CI; 0.77, 1.84] and 2.18 [1.43, 3.33] in participants with cholesterol 200 to 239 and ≥240 mg/dl, respectively (reference: cholesterol <200). In the M-I group, the corresponding HRs did not vary significantly by cholesterol level. In conclusion, the presence of M-I modifies the risk relationship between cholesterol level and CVD in African Americans with hypertensive CKD. PMID:20864686

76 FR 61432 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... for Halting Trading in All Stocks Due to Extraordinary Market Volatility September 28, 2011. Pursuant... 11.18, entitled ``Trading Halts Due to Extraordinary Market Volatility,'' to revise the current methodology for determining when to halt trading in all stocks due to extraordinary market volatility. The...

76 FR 61466 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

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Review of 5 years of a combined dietary and physical fitness intervention for control of serum cholesterol

NASA Technical Reports Server (NTRS)

Angotti, C. M.; Levine, M. S.

1994-01-01

A chart review covering the first 5 years of clinical experience with a combined dietary and exercise intervention program for the reduction of hypercholesterolemia at the National Aeronautics and Space Administration headquarters demonstrated the program's success in maintaining high-density lipoprotein cholesterol (HDL-C) levels while significantly lowering total serum cholesterol levels. This combined program also resulted in improved ratios of total serum cholesterol to HDL-C and lowered levels of low-density lipoprotein cholesterol, thus further reducing the risk for cardiovascular disease. The National Aeronautics and Space Administration Cardiovascular Risk Reduction Program was developed after it was determined that although dietary intervention alone improved total cholesterol levels, it often resulted in a more than proportionate decrease in HDL-C and a worsening of the ratio of cholesterol to HDL-C. An approach was needed that would positively affect all factors of the lipid profile. The findings from the program indicate that reduction of cardiovascular risk can be accomplished easily and effectively at the worksite through dietary intervention, personal monitoring, and a reasonable exercise program.

Addition of Garlic Extract in Ration to Reduce Cholesterol Level of Broiler

NASA Astrophysics Data System (ADS)

Utami, M. M. D.; Pantaya, D.; Agus, A.

2018-01-01

The purpose of this research is to know the effect of garlic extract (GE) in reducing cholesterol level of broiler chicken by analyzing cholesterol level of broiler chicken blood. Two hundred one day broiler age were used in this study for 35 days. The chickens were randomly divided into four treatments, each treatment consist of five replications and each repetition consist of ten chickens. This research is used completely randomized design, such as: T0: 0% EBP, T1: 2%, T2: 4% and T3: 6%. Furthermore, at age 35 days each chicken was taken blood to be analyzed cholesterol levels, low density lipoprotein (LDL), high density lipoprotein (HDL) and calculated the ratio of LDL and HDL levels. The data obtained were analyzed using software from Statistical Product and Service Solution (SPSS 16.0). The results of significant analysis continued by Duncan’s New Multiple Range Test. Addition of GE from the 2% level decreases (P <0.05) of LDL and total cholesterol, and increases HDL and HDL-LDL ratio. The conclusions is obtained garlic extract plays an important role in lowering cholesterol levels of broiler meat.

Cholesterol blocks spontaneous insertion of membrane proteins into liposomes of phosphatidylcholine.

PubMed

Nakamura, Shota; Suzuki, Sonomi; Saito, Hiroaki; Nishiyama, Ken-Ichi

2018-04-01

Spontaneous insertion of membrane proteins into liposomes formed from Escherichia coli polar phospholipids is blocked by diacylglycerol (DAG) at a physiological level. We found that cholesterol also blocks this spontaneous insertion, although a much larger amount is necessary for sufficient blockage. Reversely, sphingomyelin enhanced the spontaneous insertion. DAG at a physiological level was found not to block spontaneous insertion into liposomes formed from phosphatidylcholine (PC), while non-physiologically high concentrations of DAG reduced it. On the other hand, cholesterol blocked the spontaneous insertion into PC liposomes at a physiological level, explaining that both PC and cholesterol are absent in E. coli. While sphingomyelin did not enhance spontaneous insertion into PC liposomes, the effect of cholesterol on blockage of spontaneous insertion was dominant over that of sphingomyelin, suggesting that cholesterol functions as a blocker of disordered spontaneous insertion in eukaryotic cells. Lower amount of cholesterol was necessary to block spontaneous insertion into ER-mimic liposomes, explaining that ER membranes contain less amount of cholesterol. These results also explain that cholesterol, but not DAG, is involved in blockage of spontaneous insertion in eukaryotic cells, since DAG plays an important role as a second messenger in signal transduction.

Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite.

PubMed

Bruno, R; Arnold, C; Jacobson, L; Winick, M; Wynder, E

1983-07-01

Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels. This paper reports such a positive response to a nonpharmacologic, behavioral education program at the worksite. Employees at the New York Telephone Company corporate headquarters were assigned randomly to treatment and control groups. Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours. It comprised a multiple-treatment approach--food behavior change techniques combined with nutrition education, physical activity planning, and self-management skills. The treatment group showed substantial change compared with the control group at the program's completion. Those treated displayed a significant 6.4% reduction in total serum cholesterol (266 mg% average at baseline) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels. A significant increase in nutrition knowledge and moderate weight loss were also documented for this group. The magnitudes of a participant's baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels. Over the same period, decreases in high-density lipoprotein levels and no changes in serum cholesterol, weight, and nutrition knowledge were observed for the control group. Overall, participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight. Directions for future study are suggested.

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

PubMed Central

2013-01-01

Background 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. Methods 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). Results 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). Conclusions 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. PMID:24161017

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

PubMed

Kim, Sangmi; Kim, Joohee; Lim, Yeni; Kim, You Jin; Kim, Ji Yeon; Kwon, Oran

2016-05-13

Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. WHO International Clinical Trials Registry Platform ( KCT0000258 ).

THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

PubMed Central

Hirsch, Robert L.; Kellner, Aaron

1956-01-01

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids. PMID:13332177

Enterococcus faecium WEFA23 from infant lessens high-fat-diet-induced hyperlipidemia via cholesterol 7-alpha-hydroxylase gene by altering the composition of gut microbiota in rats.

PubMed

Huang, Fuqing; Zhang, Fen; Xu, Di; Zhang, Zhihong; Xu, Feng; Tao, Xueying; Qiu, Liang; Wei, Hua

2018-06-20

Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol.

PubMed

Kariv-Inbal, Zehavit; Yacobson, Shiri; Berkecz, Robert; Peter, Maria; Janaky, Tamas; Lütjohann, Dieter; Broersen, Laus M; Hartmann, Tobias; Michaelson, Daniel M

2012-01-01

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (ω3)), a major brain polyunsaturated fatty acid, is protective for AD and that elevated cholesterol levels are an AD risk factor. We presently investigated the extent to which the pathological effects of apoE4 in vivo can be prevented by consuming fish oil (DHA) or can be modified by cholesterol. Accordingly, apoE3- and apoE4-targeted replacement mice were subjected, following weaning, to a fish oil diet enriched in DHA and to a cholesterol-containing diet under regular and enriched environments. Cholesterol metabolism in the hippocampus and the corresponding phospholipid and fatty acid levels were affected by fish oil (DHA) and cholesterol diets and by environmental stimulation. Importantly, cholesterol metabolism and the fatty acid levels were not affected by apoE4. The phospholipid levels were, however, affected by apoE4. This effect was most pronounced in the cholesterol-fed mice and was abolished by the fish oil (DHA) diet. ApoE4 elevated hippocampal intraneuronal amyloid-β levels under regular conditions and lowered them following environmental stimulation, relative to those of the apoE3 mice. ApoE4 also elevated the levels of the presynaptic transporters Vglut and Vgat, and decreased behavioral performance in an object recognition test. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD.

75 FR 33869 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... Rule Change Relating to Trading Halts in Foreign Currency Options Under Rule 133 June 7, 2010. Pursuant... Substance of the Proposed Rule Change The Exchange proposes to amend Rule 133, Trading Halts Due to... 133 provides that trading in securities (other than FCOs) shall halt on the Exchange and shall not...

HALT Selected Papers, 1993 with Language Teaching Ideas from Paradise.

ERIC Educational Resources Information Center

Chandler, Paul, Ed.; Hodnett, Edda, Ed.

In section I, papers presented at the Hawaii Association of Language Teachers (HALT) in 1993 are presented. Section II includes a number of projects received from a call for papers simultaneous to the call for the HALT papers. Section 1 contains: "This is Like a Foreign Language to Me: Keynote Address" (Bill VanPatten); "From Discussion Questions…

Regulation of Kv7.2/Kv7.3 channels by cholesterol: Relevance of an optimum plasma membrane cholesterol content.

PubMed

Delgado-Ramírez, Mayra; Sánchez-Armass, Sergio; Meza, Ulises; Rodríguez-Menchaca, Aldo A

2018-05-01

Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment. Surprisingly, Kv7.2/Kv7.3 channels were also inhibited by membrane cholesterol loading with the MβCD/cholesterol complex. Depletion or enrichment of plasma membrane cholesterol differentially affected the biophysical parameters of the macroscopic Kv7.2/Kv7.3 currents. These results indicate a complex mechanism of Kv7.2/Kv7.3 channels modulation by membrane cholesterol. We propose that inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol depletion involves a loss of a direct cholesterol-channel interaction. However, the inhibition of Kv7.2/Kv7.3 channels by membrane cholesterol enrichment could include an additional direct cholesterol-channel interaction, or changes in the physical properties of the plasma membrane. In summary, our results indicate that an optimum cholesterol level in the plasma membrane is required for the proper functioning of Kv7.2/Kv7.3 channels. Copyright © 2018 Elsevier B.V. All rights reserved.

Cinnamon improves glucose and lipids of people with type 2 diabetes.

PubMed

Khan, Alam; Safdar, Mahpara; Ali Khan, Mohammad Muzaffar; Khattak, Khan Nawaz; Anderson, Richard A

2003-12-01

The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes. A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period. After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant. The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

Effect of a modified guar gum preparation on glucose and lipid levels in diabetics and healthy volunteers.

PubMed

Smith, U; Holm, G

1982-10-01

Six healthy volunteers and 17 diabetics (6 insulin-dependent and 11 diet- and tablet-treated) were treated with a special processed, palatable guar gum (10 g b.i.d. immediately before meals) for periods of one or three weeks or, in some cases, up to 13 weeks. A standardized test meal was given to study the effect of the fiber on postprandial glucose levels. Ten g guar was stirred in water and taken immediately before the test meal. The postprandial blood glucose levels were similar in the healthy volunteers but significantly lower in the diabetics following treatment with guar for one and three weeks, respectively. Furthermore, the fasting blood glucose levels were significantly lower in the diabetics after three, but not one, weeks of treatment. The lower postprandial glucose levels were coupled with attenuated and delayed insulin levels in accordance with an effect of guar gum on the rate of carbohydrate absorption. The cholesterol levels were on average reduced with 14% in the diabetics following three weeks' treatment with guar. The higher the initial cholesterol level, the greater the reduction in cholesterol; 26% reduction was achieved in four patients with initial levels above 7 mM. The alpha-lipoprotein cholesterol levels were not significantly changed, thus an increase in the alpha-lipoprotein cholesterol/total serum cholesterol ratio was obtained. Neither plasma triglycerides nor body weights altered during treatment. The reported side-effects were as expected and were usually mild and transient (e.g. increased flatulence). The data show that guar gum also reduces postprandial glucose levels on a long-term basis and may improve the diabetic control. Additionally, treatment with this fiber leads to a concentration-dependent decrease in cholesterol levels.

Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.

PubMed

Zhang, Li; Rajbhandari, Prashant; Priest, Christina; Sandhu, Jaspreet; Wu, Xiaohui; Temel, Ryan; Castrillo, Antonio; de Aguiar Vallim, Thomas Q; Sallam, Tamer; Tontonoz, Peter

2017-10-25

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.

Association of ADRB2 polymorphism with triglyceride levels in Tongans.

PubMed

Naka, Izumi; Ohashi, Jun; Kimura, Ryosuke; Inaoka, Tsukasa; Matsumura, Yasuhiro

2013-07-23

Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.

Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer’s Disease

PubMed Central

Pan, Yongming; Xu, Jianqin; Chen, Cheng; Chen, Fangming; Jin, Ping; Zhu, Keyan; Hu, Chenyue W.; You, Mengmeng; Chen, Minli; Hu, Fuliang

2018-01-01

Alzheimer’s disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD. PMID:29556189

Treating elevated cholesterol levels: the great Satan in perspective.

PubMed

Gibaldi, M; Kradjan, W

1996-03-01

The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention.

Blood Cholesterol Measurement in Clinical Laboratories in the United States. Current Status. A Report from the Laboratory Standardization Panel of the National Cholesterol Education Program.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

Precise and accurate cholesterol measurements are required to identify and treat individuals with high blood cholesterol levels. However, the current state of reliability of blood cholesterol measurements suggests that considerable inaccuracy in cholesterol testing exists. This report describes the Laboratory Standardization Panel findings on the…

Prevalence of Low High-density Lipoprotein Cholesterol Among Adults, by Physical Activity: United States, 2011-2014.

PubMed

Zwald, Marissa L; Akinbami, Lara J; Fakhouri, Tala H I; Fryar, Chryl D

2017-03-01

Data from the National Health and Nutrition Examination Survey •The prevalence of low high-density lipoprotein (HDL) cholesterol was significantly higher among adults who did not meet recommended physical activity guidelines (21.0%) than adults who met the guidelines (17.7%). •Low HDL cholesterol prevalence differed significantly for both men and women by adherence to physical activity guidelines. •Prevalence of low HDL cholesterol declined as age increased for both those who did and did not meet the physical activity guidelines. •Non-Hispanic white and non-Hispanic black adults who did not meet the physical activity guidelines had a higher prevalence than those who met the guidelines. •Low HDL cholesterol prevalence declined with increasing education level regardless of adherence to physical activity guidelines. Regular physical activity can improve cholesterol levels among adults, including increasing high-density lipoprotein (HDL) cholesterol (1). HDL cholesterol is known as "good" cholesterol because high levels can reduce cardiovascular disease risk (2). The 2008 Physical Activity Guidelines for Americans recommend that adults engage in 150 minutes or more of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination (3). Adherence to these guidelines is expected to decrease the prevalence of low HDL cholesterol levels (4-8). This report presents national data for 2011-2014 on low HDL cholesterol prevalence among U.S. adults aged 20 and over, by whether they met these guidelines. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Analysis of lipid profile and atherogenic index in hyperlipidemic rat (Rattus norvegicus Berkenhout, 1769) that given the methanolic extract of Parijoto (Medinilla speciosa)

NASA Astrophysics Data System (ADS)

Sa'adah, Noor Nailis; Purwani, Kristanti Indah; Nurhayati, Awik Puji Dyah; Ashuri, Nova Maulidina

2017-06-01

Diet of high lipids cause hyperlipidemia, which marked by an increase of total cholesterols, triglycerides, LDL-C, and decreasing of HDL-C. Hyperlipidemia lead the occurrence of atherosclerosis, one of factors that trigger cardiovascular disease, as hypertention; coronary heart and stroke. Parijoto (M. speciosa) is endemic plants in Asia with a distribution center in Malaysia, Indonesia and Philippines. Parijoto contain phytochemical components such as flavonoids, saponins and kardenolin. Flavonoid potensial as an antioxidants and can improve the hyperlipidemia condition. This study was aimed to determine lipid profiles and atherogenic index of hyperlipidemic Wistar rats (R. norvegicus Berkenhout, 1769) which given the methanolic extract of Parijoto (M. speciosa). The research was done with pre and post test randomized control group design. Rats were given a mixture of duck yolk and reused cooking oil (1:1) orally as much as 1% of body weight (BW) for 30 days. After hyperlipidemia achieved, rats were divided into 5 group: normal rats, hyperlipidemic rats, hyperlipidemic rats were given the methanolic extract of Parijoto (M. speciosa) 500 mg/kg, 1000 mg/kg, and 1500 mg/kg BW. Blood samples were collected when rats in hyperlipidemia conditions and after treatment with the methanolic extract of Parijoto (M. speciosa) for 30 days. The data of total cholesterol, HDL-Cholesterol, LDL-Cholesterol level, and atherogenic index were analyzed using ANOVA followed by Tukey test at 5% significance level. The result showed that giving of methanolic extract of Parijoto (M. speciosa) in hyperlipidemic rats reduced the total cholesterol, LDL-Cholesterol levels, and increased of HDL-cholesterol levels significantly (p<0.01), so atherogenic index reduced significantly too (p<0.01). Total cholesterol and LDL-Cholesterol levels were positively correlated with the atherogenic index, whereas HDL-cholesterol levels were negatively correlated with the atherogenic index.

Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels.

PubMed

Borzyszkowska, Joanna; Stanislawska-Sachadyn, Anna; Wirtwein, Marcin; Sobiczewski, Wojciech; Ciecwierz, Dariusz; Targonski, Radoslaw; Gruchala, Marcin; Rynkiewicz, Andrzej; Limon, Janusz

2012-05-01

This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P(Kruskal-Wallis) = 0.008; P(adjusted) = 0.009), high level of LDL cholesterol (P(Kruskal-Wallis) = 0.016; P(adjusted) = 0.028) and low level of HDL cholesterol (P(Kruskal-Wallis) = 0.04; P(adjusted) = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD.

Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1.

PubMed

Lv, Yun-cheng; Yang, Jing; Yao, Feng; Xie, Wei; Tang, Yan-yan; Ouyang, Xin-ping; He, Ping-ping; Tan, Yu-lin; Li, Liang; Zhang, Min; Liu, Dan; Cayabyab, Francisco S; Zheng, Xi-Long; Tang, Chao-ke

2015-05-01

Diosgenin (Dgn), a structural analogue of cholesterol, has been reported to have the hypolipidemic and antiatherogenic properties, but the underlying mechanisms are not fully understood. Given the key roles of macrophages in cholesterol metabolism and atherogenesis, it is critical to investigate macrophage cholesterol efflux and development of atherosclerotic lesion after Dgn treatment. This study was designed to evaluate the potential effects of Dgn on macrophage cholesterol metabolism and the development of aortic atherosclerosis, and to explore its underlying mechanisms. Dgn significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) protein, but didn't affect liver X receptor α levels in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by western blotting. The miR-19b levels were markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells. Cholesterol transport assays revealed that treatment with Dgn alone or together with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux, resulting in the reduced levels of total cholesterol, free cholesterol and cholesterol ester as determined by high-performance liquid chromatography. The fecal 3H-sterol originating from cholesterol-laden MPMs was increased in apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b. Treatment with Dgn alone or together with antagomiR-19b elevated plasma high-density lipoprotein levels, but reduced plasma low-density lipoprotein levels. Accordingly, aortic lipid deposition and plaque area were reduced, and collagen content and ABCA1 expression were increased in mice treated with Dgn alone or together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid-lowering and atheroprotective effects induced by Dgn. The present study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and inhibits aortic atherosclerosis progression by suppressing macrophage miR-19b expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

PubMed

Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

2018-01-01

Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol homeostasis.

PubMed

Millard, E E; Srivastava, K; Traub, L M; Schaffer, J E; Ory, D S

2000-12-08

The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic reticulum and the rate of delivery of endosomal cholesterol to the plasma membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol synthesis. Inhibition of cholesterol synthesis results in marked redistribution of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1 in internalization of PM cholesterol. Despite elevated total cellular cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be attributable to both resistance to oxysterol suppression of sterol-regulated gene expression and to reduced endoplasmic reticulum cholesterol levels under basal conditions. Taken together, these studies provide important new insights into the role of NPC1 in the determination of the levels and distribution of cellular cholesterol.

Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial Hypercholesterolemia.

PubMed

Won, Jane I; Zhang, Jun; Tecson, Kristen M; McCullough, Peter A

2017-01-01

Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen. Both of these treatments reduce total cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases of HoFH.

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters[S

PubMed Central

Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

2017-01-01

The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI. PMID:27940481

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.

PubMed

Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

2017-02-01

The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI.

Cholesterol in islet dysfunction and type 2 diabetes

PubMed Central

Brunham, Liam R.; Kruit, Janine K.; Verchere, C. Bruce; Hayden, Michael R.

2008-01-01

Type 2 diabetes (T2D) frequently occurs in the context of abnormalities of plasma lipoproteins. However, a role for elevated levels of plasma cholesterol in the pathogenesis of this disease is not well established. Recent evidence suggests that alterations of plasma and islet cholesterol levels may contribute to islet dysfunction and loss of insulin secretion. A number of genes involved in lipid metabolism have been implicated in T2D. Recently an important role for ABCA1, a cellular cholesterol transporter, has emerged in regulating cholesterol homeostasis and insulin secretion in pancreatic β cells. Here we review the impact of cholesterol metabolism on islet function and its potential relationship to T2D. PMID:18246189

Work, sleep, and cholesterol levels of U.S. long-haul truck drivers

PubMed Central

LEMKE, Michael K.; APOSTOLOPOULOS, Yorghos; HEGE, Adam; WIDEMAN, Laurie; SÖNMEZ, Sevil

2016-01-01

Long-haul truck drivers in the United States experience elevated cardiovascular health risks, possibly due to hypercholesterolemia. The current study has two objectives: 1) to generate a cholesterol profile for U.S. long-haul truck drivers; and 2) to determine the influence of work organization characteristics and sleep quality and duration on cholesterol levels of long-haul truck drivers. Survey and biometric data were collected from 262 long-haul truck drivers. Descriptive analyses were performed for demographic, work organization, sleep, and cholesterol measures. Linear regression and ordinal logistic regression analyses were conducted to examine for possible predictive relationships between demographic, work organization, and sleep variables, and cholesterol outcomes. The majority (66.4%) of drivers had a low HDL (<40 mg/dL), and nearly 42% of drivers had a high-risk total cholesterol to HDL cholesterol ratio. Sleep quality was associated with HDL, LDL, and total cholesterol, and daily work hours were associated with LDL cholesterol. Workday sleep duration was associated with non-HDL cholesterol, and driving experience and sleep quality were associated with cholesterol ratio. Long-haul truck drivers have a high risk cholesterol profile, and sleep quality and work organization factors may induce these cholesterol outcomes. Targeted worksite health promotion programs are needed to curb these atherosclerotic risks. PMID:28049935

Pla2g12b and Hpn Are Genes Identified by Mouse ENU Mutagenesis That Affect HDL Cholesterol

PubMed Central

Aljakna, Aleksandra; Choi, Seungbum; Savage, Holly; Hageman Blair, Rachael; Gu, Tongjun; Svenson, Karen L.; Churchill, Gary A.; Hibbs, Matt; Korstanje, Ron

2012-01-01

Despite considerable progress understanding genes that affect the HDL particle, its function, and cholesterol content, genes identified to date explain only a small percentage of the genetic variation. We used N-ethyl-N-nitrosourea mutagenesis in mice to discover novel genes that affect HDL cholesterol levels. Two mutant lines (Hlb218 and Hlb320) with low HDL cholesterol levels were established. Causal mutations in these lines were mapped using linkage analysis: for line Hlb218 within a 12 Mbp region on Chr 10; and for line Hlb320 within a 21 Mbp region on Chr 7. High-throughput sequencing of Hlb218 liver RNA identified a mutation in Pla2g12b. The transition of G to A leads to a cysteine to tyrosine change and most likely causes a loss of a disulfide bridge. Microarray analysis of Hlb320 liver RNA showed a 7-fold downregulation of Hpn; sequencing identified a mutation in the 3′ splice site of exon 8. Northern blot confirmed lower mRNA expression level in Hlb320 and did not show a difference in splicing, suggesting that the mutation only affects the splicing rate. In addition to affecting HDL cholesterol, the mutated genes also lead to reduction in serum non-HDL cholesterol and triglyceride levels. Despite low HDL cholesterol levels, the mice from both mutant lines show similar atherosclerotic lesion sizes compared to control mice. These new mutant mouse models are valuable tools to further study the role of these genes, their affect on HDL cholesterol levels, and metabolism. PMID:22912808

Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

PubMed

Olatunji, L A; Soladoye, A O

2007-06-01

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

Effect of Hypercholesterolemia on Fatty Infiltration and Quality of Tendon-to-Bone Healing in a Rabbit Model of a Chronic Rotator Cuff Tear: Electrophysiological, Biomechanical, and Histological Analyses.

PubMed

Chung, Seok Won; Park, HaeBong; Kwon, Jieun; Choe, Ghee Young; Kim, Sae Hoon; Oh, Joo Han

2016-05-01

The incidence of healing failure after rotator cuff repair is high, and fatty infiltration is a crucial factor in healing failure. To verify the effect of hypercholesterolemia on fatty infiltration and the quality of tendon-to-bone healing and its reversibility by lowering the cholesterol level in a chronic tear model using the rabbit supraspinatus. Controlled laboratory study. Forty-eight rabbits were randomly allocated into 4 groups (n = 12 each). After 4 weeks of a high-cholesterol diet (groups A and B) and a regular diet (groups C and D), the supraspinatus tendon was detached and left alone for 6 weeks and then was repaired in a transosseous manner (groups A, B, and C). Group D served as a control. Group A continued to receive the high-cholesterol diet until the final evaluation (6 weeks after repair); however, at the time of repair, group B was changed to a general diet with administration of a cholesterol-lowering agent (simvastatin). Histological evaluation of the fat-to-muscle proportion was performed twice, at the time of repair and the final evaluation, and an electromyographic (EMG) test, mechanical test, and histological test of tendon-to-bone healing were performed at the final evaluation. For the EMG test, group A showed a significantly smaller area of compound muscle action potential compared with groups C and D (all P <.01), and group B showed a larger area than group A, almost up to the level of group C (P = .312). Similarly, group A showed significantly lower mechanical properties both in load-to-failure and stiffness compared with groups C and D (all P <.05). In addition, although not significantly different, the mechanical properties of group B were higher than those of group A (mean load-to-failure: group A = 42.01 N, group B = 58.23 N [P = .103]; mean stiffness: group A = 36.32 N/mm, group B = 47.22 N/mm [P = .153]). For the histological test, groups A and B showed a significantly higher fat-to-muscle proportion than did groups C and D at 6 weeks after detachment (all P <.05), but at the final evaluation, group B showed a decreased fat-to-muscle proportion (mean ± SD: from 64.02% ± 11.87% to 54.68% ± 10.47%; P = .146) compared with group A, which showed increased fat-to-muscle proportion (from 59.26% ± 17.80% to 78.23% ± 10.87%; P = .015). Groups B and C showed better tendon-to-bone interface structures than did group A, which showed coarse and poorly organized collagen fibers with fat interposition. Hypercholesterolemia had a deleterious effect on fatty infiltration and the quality of tendon-to-bone repair site, and lowering hypercholesterolemia seemed to halt or reverse these harmful effects in this experimental model. Systemic diseases such as hypercholesterolemia should be tightly controlled during the perioperative period of rotator cuff repair. © 2016 The Author(s).

Six Steps to a Sustainable Society. Worldwatch Paper 48.

ERIC Educational Resources Information Center

Brown, Lester R.; Shaw, Pamela

This paper discusses six steps which must be taken on a global level to put society on a sustainable path. Of the various steps none is more important than bringing population growth to a halt. The official United Nations medium-level population projects, used by planners throughout the world, show world population reaching some 10.5 billion…

The effect of cholesterol overload on mouse kidney and kidney-derived cells.

PubMed

Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko

2018-11-01

Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman's capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

High blood cholesterol levels

MedlinePlus

Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... A cholesterol test is done to diagnose a lipid disorder. Different experts recommend different starting ages. Recommended ...

TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

PubMed

Moreno-Navarrete, José María; Moreno, María; Ortega, Francisco; Xifra, Gemma; Hong, Shangyu; Asara, John M; Serrano, José C E; Jové, Mariona; Pissios, Pavlos; Blüher, Matthias; Ricart, Wifredo; Portero-Otin, Manuel; Fernández-Real, José Manuel

2017-10-01

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β ( TSHB ) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, N -stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up-regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT.-Moreno-Navarrete, J. M., Moreno, M., Ortega, F., Xifra, G., Hong, S., Asara, J. M., Serrano, J. C. E., Jové, M., Pissios, P., Blüher, M., Ricart, W., Portero-Otin, M., Fernández-Real, J. M. TSHB mRNA is linked to cholesterol metabolism in adipose tissue. © FASEB.

National Survey on Internal Quality Control Practice for Lipid Parameters in Laboratories of China from 2014 to 2016.

PubMed

Ye, Yuanyuan; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2017-09-01

To investigate the situation of Internal Quality Control (IQC) practice for total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from 2014 to 2016 in laboratories in China and provide improvement measurements. A web-based External Quality Assessment (EQA) system was used to collect IQC data of lipid parameters in laboratories which continuously participated in the national EQA programs in China from 2014 to 2016. Pass rate of the coefficients of variation (CVs) of two level quality controls in four lipid parameters were calculated according to six quality specifications for precision to evaluate the current status of precision level of the four lipid parameters and their change over time in China. 533, 512, 504, and 466 laboratories continuously reported the data of level one for total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol, and 212, 210, 208 and 198 laboratories reported the level two, respectively. The percentage of laboratories meeting the quality specification varied based on different criteria. Non-significant change can be found in the pass rate of CVs over time. The number of laboratories using a closed system increased over time, but still only accounted for a small proportion. There is no significant difference in the pass rate of CVs between closed and open systems. Triglycerides currently have a fairly good performance in China. While the performance of laboratories on total cholesterol, HDL-cholesterol and LDL-cholesterol has yet to be improved.

Impact of a public cholesterol screening program.

PubMed

Fischer, P M; Guinan, K H; Burke, J J; Karp, W B; Richards, J W

1990-12-01

The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease.

The effects of coffee consumption on serum lipids and lipoprotein in healthy individuals.

PubMed

Onuegbu, A J; Agbedana, E O

2001-01-01

The changes in total serum cholestrol, serum triglyceride, HDL-cholesterol and LDL-cholesterol after twenty eight (28) days of consumption of moderate quantity of a commercial coffee preparation (NESCAFE brand) were studied in 30 human subjects consisting of 20 male and 10 female healthy adults. Significant increases in the mean total serum cholesterol concentration (110.8-126.5 mg/100 mls) and LDL- cholesterol concentration (78.4-94.5 mg/100 ml) were observed in the subjects. No significant differences were obtained in the mean HDL cholesterol concentration and in the mean serum triglyceride levels. The differences observed in the mean total serum cholesterol, LDL cholesterol, HDL- cholesterol and triglyceride concentrations in the individual male and female groups studied were not statistically significant. The results from this study suggest that short-term consumption of coffee may increase the total serum cholesterol and LDL cholesterol levels. It is therefore possible that long-term consumption of coffee may lead to clinically significant alterations in serum lipid profile and could be important in the aetiology of atherosclerotic vascular diseases such as coronary heart disease.

Colorimetric detection of cholesterol based on enzyme modified gold nanoparticles

NASA Astrophysics Data System (ADS)

Nirala, Narsingh R.; Saxena, Preeti S.; Srivastava, Anchal

2018-02-01

We develop a simple colorimetric method for determination of free cholesterol in aqueous solution based on functionalized gold nanoparticles with cholesterol oxidase. Functionalized gold nanoparticles interact with free cholesterol to produce H2O2 in proportion to the level of cholesterol visually is being detected. The quenching in optical properties and agglomeration of functionalized gold nanoparticles play a key role in cholesterol sensing due to the electron accepting property of H2O2. While the lower ranges of cholesterol (lower detection limit i.e. 0.2 mg/dL) can be effectively detected using fluorescence study, the absorption study attests evident visual color change which becomes effective for detection of higher ranges of cholesterol (lower detection limit i.e. 19 mg/dL). The shades of red gradually change to blue/purple as the level of cholesterol detected (as evident at 100 mg/dL) using unaided eye without the use of expensive instruments. The potential of the proposed method to be applied in the field is shown by the proposed cholesterol measuring color wheel.

Contemporary trends in dyslipidemia in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Recent cross-sectional population studies in the United States have shown an increase in obesity, a decrease in cholesterol values, but no changes in levels of high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Plasma total cholesterol, HDL-C, and TG levels, measured by the same met...

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

USDA-ARS?s Scientific Manuscript database

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

Retinoic Acid Isomers Up-Regulate ATP Binding Cassette A1 and G1 and Cholesterol Efflux in Rat Astrocytes: Implications for Their Therapeutic and Teratogenic Effects

PubMed Central

Chen, Jing; Costa, Lucio G.

2011-01-01

Recent studies suggest that retinoids may be effective in the treatment of Alzheimer's disease, although exposure to an excess of retinoids during gestation causes teratogenesis. Cholesterol is essential for brain development, but high levels of cholesterol have been associated with Alzheimer's disease. We hypothesized that retinoic acid may affect cholesterol homeostasis in rat astrocytes, which regulate cholesterol distribution in the brain, through the up-regulation of cholesterol transporters ATP binding cassette (Abc)a1 and Abcg1. Tretinoin, 13-cis retinoic acid (13-cis-RA), 9-cis-RA, and the selective retinoid X receptor (RXR) agonist methoprene significantly increased cholesterol efflux induced by cholesterol acceptors and protein levels of Abca1 by 2.3- (±0.25), 3.6- (±0.42), 4.1- (±0.5), and 1.75- (±0.43) fold, respectively, and Abcg1 by 2.1- (±0.26), 2.2- (±0.33), 2.5- (±0.23), and 2.2- (±0.21) fold, respectively. 13-cis-RA and 9-cis-RA also significantly increased mRNA levels of Abca1 (maximal induction 7.3 ± 0.42 and 2.7 ± 0.17, respectively) and Abcg1 (maximal induction 2.0 ± 0.18 and 1.8 ± 0.09, respectively), and the levels of membrane-bound Abca1 (2.5 ± 0.3 and 2.5 ± 0.40-fold increase, respectively), whereas they significantly decreased intracellular cholesterol content without affecting cholesterol synthesis. The effect of 9-cis-RA on cholesterol homeostasis in astrocytes can be ascribed to the activation of RXR, whereas the effects of 13-cis-RA and tretinoin were independent of either RXRs or retinoic acid receptors. These findings suggest that retinoids affect cholesterol homeostasis in astrocytes and that this effect may be involved in both their therapeutic and teratogenic actions. PMID:21628419

Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

PubMed Central

Guptha, Soneil; Gupta, Rajeev; Deedwania, Prakash; Bhansali, Anil; Maheshwari, Anuj; Gupta, Arvind; Gupta, Balkishan; Saboo, Banshi; Singh, Jitendra; Achari, Vijay; Sharma, Krishna Kumar

2014-01-01

Objective To determine levels of cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians. Methods Population based 6123 subjects (men 3388) were evaluated. Mean±1SD of various cholesterol lipoproteins (total, HDL, LDL and non-HDL cholesterol) and triglycerides were reported. Subjects were classified according to US National Cholesterol Education Program. Results Age-adjusted levels in men and women were cholesterol total 178.4 ± 39 and 184.6 ± 39, HDL 44.9 ± 11 and 51.1 ± 11, LDL 102.5 ± 33 and 106.2 ± 33, total:HDL 4.15 ± 1.2 and 3.79 ± 1.0 and triglycerides 162.5 ± 83 and 143.7 ± 83 mg/dl. Age-adjusted prevalence (%) in men and women, respectively were, total cholesterol ≥200 mg/dl 25.1 and 24.9, LDL cholesterol ≥130 mg/dl 16.3 and 15.1 and ≥100 mg/dl 49.5 and 49.7, HDL cholesterol <40/<50 mg/dl 33.6 and 52.8, total:HDL cholesterol ≥4.5 29.4 and 16.8, and triglycerides ≥150 mg/dl 42.1 and 32.9%. Cholesterol level was significantly greater in subjects with better socioeconomic status, body mass index and waist circumference while triglycerides were more among those with high socioeconomic status, fat intake, body mass index and waist circumference (p < 0.05). Hypercholesterolemia awareness (15.6%), treatment (7.2%) and control (4.1%) were low. Conclusions Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol. PMID:24973832

Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms

PubMed Central

Owei, Ibiye; Umekwe, Nkiru; Wan, Jim

2016-01-01

Dyslipidemia and dysglycemia are etiologically associated, but the direction, chronology, and mechanisms of the association are not fully understood. We, therefore, analyzed data from 335 healthy adults (184 black, 151 white) enrolled in the Pathobiology of Prediabetes in A Biracial Cohort study. Subjects underwent oral glucose tolerance test (OGTT) and were enrolled if they had normal fasting and 2-h plasma glucose levels. Assessments during year 1 included anthropometry, fasting lipid profile, insulin sensitivity, and insulin secretion. Thereafter, OGTT was assessed annually for 5.5 years. The primary outcome was occurrence of prediabetes (impaired fasting glucose or impaired glucose tolerance) or diabetes. During a mean follow-up of 2.62 years, 110 participants (32.8%) developed prediabetes (N = 100) or diabetes (N = 10). In multivariate logistic regression models, higher baseline low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower HDL cholesterol levels significantly increased the risk of incident prediabetes. The combined relative risk (95% confidence interval [CI]) of prediabetes for participants with lower baseline HDL cholesterol (10th vs. 90th percentile), higher LDL cholesterol (90th vs. 10th percentile) and high triglycerides levels (90th vs. 10th percentile) was 4.12 (95% CI 1.61–10.56), P = 0.0032. At baseline, lipid values showed significant associations with measures of adiposity, glycemia, insulin sensitivity, and secretion. In both ethnic groups, waist circumference correlated positively with triglycerides and inversely with HDL cholesterol levels (P = 0.0004–<0.0001); fasting plasma glucose correlated positively with triglycerides and LDL cholesterol levels and inversely with HDL cholesterol levels (P = 0.006–<0.0001); insulin sensitivity correlated positively with HDL cholesterol and inversely with triglyceride levels (P < 0.0001), and insulin secretion correlated positively with triglycerides (P = 0.01) and inversely with HDL cholesterol (P < 0.0001). We conclude that a baseline lipidemic signature identifies normoglycemic individuals at high risk for future glycemic progression, via congruent associations with adiposity and glucoregulatory mechanisms. These findings suggest that early lifestyle intervention could ameliorate progressive dyslipidemia and dysglycemia. PMID:27430991

Mendelian randomization analysis in three Japanese populations supports a causal role of alcohol consumption in lowering low-density lipid cholesterol levels and particle numbers.

PubMed

Tabara, Yasuharu; Ueshima, Hirotsugu; Takashima, Naoyuki; Hisamatsu, Takashi; Fujiyoshi, Akira; Zaid, Maryam; Sumi, Masaki; Kohara, Katsuhiko; Miki, Tetsuro; Miura, Katsuyuki

2016-11-01

While alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers. This study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 ± 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy. Alcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p < 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean ± standard error, *1*1: 60 ± 0.5, *1*2: 56 ± 0.6, *2*2: 55 ± 1.3 mg/dl, p < 0.001) and inversely associated with LDL cholesterol level (116 ± 0.9, 124 ± 1.1, 130 ± 2.6 mg/dl, p < 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 ± 0.32 μmol/l, p < 0.001) and inversely associated with LDL particle numbers (-67.8 ± 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake. Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence and risk factors associated with the metabolic syndrome and dyslipidemia in White, Black, Amerindian and Mixed Hispanics in Zulia State, Venezuela.

PubMed

Florez, Hermes; Silva, Eglé; Fernández, Virginia; Ryder, Elena; Sulbarán, Tulio; Campos, Gilberto; Calmón, Gustavo; Clavel, Emilio; Castillo-Florez, Sumaya; Goldberg, Ronald

2005-07-01

Studies have highlighted the association between insulin resistance (IR) and several cardiovascular (CV) risk factors, including hypertension (HTN), obesity, dyslipidemia (i.e. high triglyceride and low HDL-cholesterol) and glucose intolerance, in a cluster known as the metabolic syndrome (MS). There are few data on the frequency of the MS and dyslipidemia in developing countries, and none in South America. To estimate the prevalence of the MS and its components in Zulia State, Venezuela, and to establish associated demographic and clinical factors, we evaluated 3108 Hispanic men and women aged 20 years or older from a cross-sectional survey of a random representative sample from each health district in Zulia State, Venezuela (1999-2001). Prevalence of the MS and dyslipidemia was defined according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) criteria. The age-adjusted prevalence of MS and dyslipidemia was 31.2% and 24.1%, respectively, with higher rates in men than in women. Prevalence rates increased with age and with the degree of obesity. MS prevalence was lower in Amerindian (17.%) compared to Black (27.2%), White (33.3%) and Mixed (37.4%) men, but no differences were found among women. Overall, low HDL-cholesterol (65.3%), abdominal obesity (42.9%) and HTN (38.1%) were the most frequent MS components. After adjusting for age, sex and race groups, family history of diabetes, obesity and HTN were associated with the MS. Sedentary lifestyle also increased the risk of MS, event after adjusting for the same covariates, obesity and the degree of IR. These results suggest that MS is found in approximately one-third of the Venezuelan adult population in Zulia State, with higher prevalence in men related to the presence of dyslipidemia. Lifestyle interventions in MS subjects are needed in Venezuela to halt the burden of CV disease and diabetes.

Modeling total cholesterol as predictor of mortality: the low-cholesterol paradox.

PubMed

Wesley, David; Cox, Hugh F

2011-01-01

Elevated total cholesterol is well-established as a risk factor for coronary artery disease and cardiovascular mortality. However, less attention is paid to the association between low cholesterol levels and mortality--the low cholesterol paradox. In this paper, restricted cubic splines (RCS) and complex survey methodology are used to show the low-cholesterol paradox is present in the laboratory, examination, and mortality follow-up data from the Third National Health and Nutrition Examination Survey (NHANES III). A series of Cox proportional hazard models, demonstrate that RCS are necessary to incorporate desired covariates while avoiding the use of categorical variables. Valid concerns regarding the accuracy of such predictive models are discussed. The one certain conclusion is that low cholesterol levels are markers for excess mortality, just as are high levels. Restricted cubic splines provide the necessary flexibility to demonstrate the U-shaped relationship between cholesterol and mortality without resorting to binning results. Cox PH models perform well at identifying associations between risk factors and outcomes of interest such as mortality. However, the predictions from such a model may not be as accurate as common statistics suggest and predictive models should be used with caution.

Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hershock, D.; Vogel, W.H.

1989-02-09

Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regularmore » diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.« less

Serum lipid levels for a multicultural population in Auckland, New Zealand: results from the Diabetes Heart and Health Survey (DHAH) 2002-2003.

PubMed

Gentles, Dudley; Metcalf, Patricia; Dyall, Lorna; Scragg, Robert; Sundborn, Gerhard; Schaaf, David; Black, Peter N; Jackson, Rodney T

2007-11-09

To describe mean serum lipid concentrations for Maori, Pacific people (mostly of Samoan, Tongan, Niuean, or Cook Islands origin), and Others (mostly New Zealand-born Europeans), and to identify risk factors for an adverse lipid profile. A cross-sectional survey of adults aged between 35-74 years within the Auckland area. There were 1006 Maori, 996 Pacific people, and 2021 'Others' Fasting blood samples were collected from participants, and total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured. Maori and Pacific people had similar mean serum total and LDL cholesterol levels but lower HDL levels and higher total to HDL cholesterol ratios compared to Others (adjusted for age and gender). Maori also had higher triglycerides than Others. High BMI and cigarette smoking were positively associated with unfavourable lipid profiles, while current alcohol drinking and vigorous leisure time activity were associated with increased HDL cholesterol and lower total to HDL cholesterol ratios. Over 90% of all ethnic groups had total cholesterol levels above currently accepted optimal levels (>4 mmol/L) and two-thirds were above 5 mmol/L. While 30% of Others had a total to HDL cholesterol ratio above the 'optimal' threshold of 4.5, 40% of Maori and 44% of pacific people were above this level. This is the first study to simultaneously assess lipid levels in Maori, Pacific people, and Others in one population-based study. Despite similar total and LDL cholesterol levels in all ethnic groups; overweight, obesity, and current cigarette smoking were the main risk factors for their adverse lipid profiles. Engaging in leisure-time activity and alcohol consumption (and not surprisingly lipid-lowering drugs) were associated with better lipid profiles. We confirm that the main lipid-related cardiovascular disease risk in Maori and Pacific people is due to their low HDL and high triglyceride levels.

Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

PubMed

Friday, K E; Drinkwater, B L; Bruemmer, B; Chesnut, C; Chait, A

1993-12-01

To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

Suicidal behaviour and lipid levels in unipolar and bipolar depression.

PubMed

Ainiyet, Babajohn; Rybakowski, Janusz K

2014-10-01

Evidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode. The study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24-72 h after hospital admission. Suicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol. The results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides.

Cellular cholesterol regulates ubiquitination and degradation of the cholesterol export proteins ABCA1 and ABCG1.

PubMed

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

2014-03-14

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.

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

PubMed Central

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

Linkage study of the low-density lipoprotein-receptor gene and cholesterol levels in an Afrikaner family. Quantitative genetics and identification of a minor founder effect.

PubMed

Brink, P A; Brink, L T; Torrington, M; Bester, A J

1990-03-17

Overlap of clinical and biochemical characteristics between hypercholesterolaemia in members of the general population and familial hypercholesterolaemic (FH) individuals may lead to misdiagnosis. Quantitative analysis of family data may circumvent this problem. A way of looking for an association between plasma cholesterol levels and restriction fragment length polymorphism markers (RFLP) on the low-density lipoprotein (LDL) receptor gene by using reference cholesterol distributions was explored. Linkage, with a logarithm of the odds (LOD) score of 6.8 at theta 0, was detected between cholesterol levels and the LDL receptor in an extended Afrikaner family. Two RFLP-haplotypes, one previously found in a majority of Afrikaner FH homozygotes, and a second, Stu I-, BstE II+, Pvu II+, Nco I+, were associated with high cholesterol levels in this pedigree.

Association of ADRB2 polymorphism with triglyceride levels in Tongans

PubMed Central

2013-01-01

Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Association between dietary habits, education, serum triglycerides and blood cholesterol among women of Cabildo, Buenos Aires.

PubMed

Schneider, Raul J; Barengo, Noel; Haapala, Irja; Tavella, Marcelo

2006-01-01

A cross sectional study of 107 women between 20 and 69 years old, living in the town of Cabildo, province of Buenos Aires, Argentina, which describes food intake and analyses its relation to their education, blood cholesterol and serum triglyceride levels. A food frequency questionnaire including questions regarding meal patterns and food use were completed by the participants. Questions regarding educational status were included. A nutritional risk score was created from nine food groups. Total blood cholesterol and serum triglyceride levels were determined. Average total blood cholesterol levels of the women who participated in the present study were higher (209 mg/dl) than those recommended by the National Cholesterol Education Program, while triglyceride values remained within the normal range (124 mg/dl). Total blood cholesterol levels increased with age. Bread, biscuits and cakes were consumed on a daily basis by 98% of the participants and dairy products by 92%, these being mainly full-fat. Meat and fast food intake were very high (96% and 100% respectively). Vegetable and fish intakes were higher among the more educated women. Mayonnaise (58%) and butter (43%) are popular as food dressings and bread spreads respectively, and sunflower oil was the most commonly used for cooking by 94% of the participants. Women with low educational levels (less than 7 years) had higher nutritional risk scores, and thus unhealthier dietary habits than those with more years of formal education. No statistically significant association was found between food groups and cholesterol or triglyceride levels.

HALT & REVERSE: Hsf1 activators lower cardiomyocyt damage; towards a novel approach to REVERSE atrial fibrillation.

PubMed

Lanters, Eva A H; van Marion, Denise M S; Kik, Charles; Steen, Herman; Bogers, Ad J J C; Allessie, Maurits A; Brundel, Bianca J J M; de Groot, Natasja M S

2015-11-05

Atrial fibrillation is a progressive arrhythmia, the exact mechanism underlying the progressive nature of recurrent AF episodes is still unknown. Recently, it was found that key players of the protein quality control system of the cardiomyocyte, i.e. Heat Shock Proteins, protect against atrial fibrillation progression by attenuating atrial electrical and structural remodeling (electropathology). HALT & REVERSE aims to investigate the correlation between electropathology, as defined by endo- or epicardial mapping, Heat Shock Protein levels and development or recurrence of atrial fibrillation following pulmonary vein isolation, or electrical cardioversion or cardiothoracic surgery. This study is a prospective observational study. Three separate study groups are defined: (1) cardiothoracic surgery, (2) pulmonary vein isolation and (3) electrical cardioversion. An intra-operative high-resolution epicardial (group 1) or endocardial (group 2) mapping procedure of the atria is performed to study atrial electropathology. Blood samples for Heat Shock Protein determination are obtained at baseline and during the follow-up period at 3 months (group 2), 6 months (groups 1 and 2) and 1 year (group 1 and 2). Tissue samples of the right and left atrial appendages in patients in group 1 are analysed for Heat Shock Protein levels and for tissue characteristics. Early post procedural atrial fibrillation is detected by continuous rhythm monitoring, whereas late post procedural atrial fibrillation is documented by either electrocardiogram or 24-h Holter registration. HALT & REVERSE aims to identify the correlation between Heat Shock Protein levels and degree of electropathology. The study outcome will contribute to novel diagnostic tools for the early recognition of clinical atrial fibrillation. Rotterdam Medical Ethical Committee MEC-2014-393, Dutch Trial Registration NTR4658.

TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).

PubMed

Meier, C; Staub, J J; Roth, C B; Guglielmetti, M; Kunz, M; Miserez, A R; Drewe, J; Huber, P; Herzog, R; Müller, B

2001-10-01

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.

Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population.

PubMed

Igl, Wilmar; Kamal-Eldin, Afaf; Johansson, Asa; Liebisch, Gerhard; Gnewuch, Carsten; Schmitz, Gerd; Gyllensten, Ulf

2013-01-01

The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥ 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

Association of salivary triglycerides and cholesterol with dental caries in children with type 1 diabetes mellitus.

PubMed

Subramaniam, Priya; Sharma, Akhliesh; Kaje, Keerthan

2015-01-01

Metabolic disturbances in diabetes mellitus can affect oral health. Altered levels of salivary lipids have been suggested as a risk for dental caries. There has been lack of research in this regard and in children with type 1 diabetes mellitus. To assess the salivary triglycerides and cholesterol levels in children with type 1 diabetes mellitus and correlate them with their dental caries status. Thirty children aged 12-16 years with type 1 diabetes mellitus and 30 age- and gender-matched healthy children were included in the study. Unstimulated saliva was collected from each child and evaluated for salivary triglyceride and cholesterol levels. Dental caries status (DMFT) was recorded. Salivary cholesterol and triglyceride levels were significantly higher in children with type 1 diabetes mellitus (p ≤ 0.05). In comparison to controls, mean DMFT score was higher in the diabetic children. Salivary triglycerides showed a significant correlation with dental caries status in the study group (p = 0.035). In normal children, salivary cholesterol levels showed a significant association with dental caries. (p = 0.008). Both salivary cholesterol and triglycerides levels were significantly higher in children with type 1 diabetes mellitus. Salivary triglycerides showed a significant association with dental caries in these children. © 2014 Special Care Dentistry Association and Wiley Periodicals, Inc.

Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

PubMed Central

Lavoie, Jean-Marc

2016-01-01

Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative. PMID:27621762

Prevalence of dyslipidemia according to the nutritional status in a representative sample of São Paulo.

PubMed

Garcez, Marcela Riccioppo; Pereira, Jaqueline Lopes; Fontanelli, Mariane de Mello; Marchioni, Dirce Maria Lobo; Fisberg, Regina Mara

2014-12-01

Overweight is one of the major public health problems in Brazil; it is associated with dyslipidemia, which is an important risk factor for cardiovascular diseases. To evaluate the lipid profile of residents of the municipality of São Paulo, state of São Paulo, according to the nutritional status. Data from the population-based cross-sectional study ISA-Capital 2008 on a sample of residents of São Paulo were used. Participants were categorized into groups according to body mass index and age range. The levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and non-HDL cholesterol were measured. The association between lipid profile, nutricional status, and waist circumference was investigated. The data were processed using the survey mode of the Stata 11.0 software. The prevalence of any type of dyslipidemia in the population was 59.74%, with low HDL-cholesterol dyslipidemia being the most common type. Not overweight individuals had higher mean levels of HDL-cholesterol and lower levels of LDL-cholesterol, total cholesterol, triglycerides, and non-HDL cholesterol when compared with the overweight group. The rate of inadequacy of these variables was higher in the overweight individuals, regardless of the age group, to the exception of LDL-cholesterol in the adults and elderly. A higher prevalence of isolated hypertriglyceridemia was observed in individuals with higher waist circumference among the adults and the total population. The results indicate an association between dyslipidemia and overweight in the population of the city of São Paulo. The most prevalent dyslipidemia in this population was low HDL-cholesterol.

Preferential invasion of mitotic cells by Salmonella reveals that cell surface cholesterol is maximal during metaphase.

PubMed

Santos, António J M; Meinecke, Michael; Fessler, Michael B; Holden, David W; Boucrot, Emmanuel

2013-07-15

Cell surface-exposed cholesterol is crucial for cell attachment and invasion of many viruses and bacteria, including the bacterium Salmonella, which causes typhoid fever and gastroenteritis. Using flow cytometry and 3D confocal fluorescence microscopy, we found that mitotic cells, although representing only 1-4% of an exponentially growing population, were much more efficiently targeted for invasion by Salmonella. This targeting was not dependent on the spherical shape of mitotic cells, but was instead SipB and cholesterol dependent. Thus, we measured the levels of plasma membrane and cell surface cholesterol throughout the cell cycle using, respectively, brief staining with filipin and a fluorescent ester of polyethylene glycol-cholesterol that cannot flip through the plasma membrane, and found that both were maximal during mitosis. This increase was due not only to the rise in global cell cholesterol levels along the cell cycle but also to a transient loss in cholesterol asymmetry at the plasma membrane during mitosis. We measured that cholesterol, but not phosphatidylserine, changed from a ∼2080 outerinner leaflet repartition during interphase to ∼5050 during metaphase, suggesting this was specific to cholesterol and not due to a broad change of lipid asymmetry during metaphase. This explains the increase in outer surface levels that make dividing cells more susceptible to Salmonella invasion and perhaps to other viruses and bacteria entering cells in a cholesterol-dependent manner. The change in cholesterol partitioning also favoured the recruitment of activated ERM (Ezrin, Radixin, Moesin) proteins at the plasma membrane and thus supported mitotic cell rounding.

Optimization of bioactive compounds in buckwheat sprouts and their effect on blood cholesterol in hamsters.

PubMed

Lin, Li-Yun; Peng, Chiung-Chi; Yang, Ya-Lu; Peng, Robert Y

2008-02-27

Nutrient levels in buckwheats that were maximized in day 8 sprouts (D8SP) included total phenolics, quercetin, and l-ascorbic acid, whereas those of oxalic, malic, tartaric, and citric acids, rutin, and gamma-aminobutyric acid (GABA) were found to reach maximum levels on day 10. Ethanolic extract of D8SP (2.5 mg/mL) revealed potent free-radical scavenging (FRS) and antioxidative (ANO) capabilities. However, its Fe2+-chelating capability was only moderate. To further study the hypolipidemic activity of D8SP, 36 Syrian hamsters were grouped into six groups and fed for 28 days, respectively, with (i) control meal, (ii) high fat plus high cholesterol meal, (iii) high fat plus high cholesterol plus 2.5% of buckwheat seeds, (iv) high fat plus high cholesterol plus 25% of buckwheat seeds, (v) high fat plus high cholesterol plus 2.5% of D8SP, and (vi) high fat plus high cholesterol plus 25% of D8SP. High seed meal prominently enhanced body weight gain, whereas high sprout meal exhibited the highest feed efficiency. Ratios of liver/body weight (L/B) were significantly lowered by all BS meals. Although low seed meal reduced serum total cholesterol (TC) levels (p<0.05), its effect was still inferior to the high seed and sprout meals (p<0.01). In contrast, serum triglyceride (TG) levels were lowered only by the high seed and sprout meals (p<0.05). Alternatively, levels of serum low-density lipoprotein cholesterol (LDL-C) were significantly suppressed by all buckwheat meals (p<0.01). Serum high-density lipoprotein cholesterol (HDL-C) levels were increased, however, insignificantly. Nutraceutically more meaningful is that both LDL-C/HDL-C and TC/HDL-C ratios were significantly lowered (p<0.01). Apparently, hepatic TC levels were significantly reduced, whereas hepatic TG levels were totally unaffected. Conclusively, sprouting triggers a variety of nutritional changes in buckwheats. Day 8 sprouts, consisting of high polyphenolic and moderate quercetin contents, are nutraceutically maximized when hypocholesterolemic, hypotriglyceridemic, and antioxidative activities are concerned.

Reversible effects of sphingomyelin degradation on cholesterol distribution and metabolism in fibroblasts and transformed neuroblastoma cells.

PubMed Central

Pörn, M I; Slotte, J P

1990-01-01

Plasma-membrane sphingomyelin appears to be one of the major determinants of the preferential allocation of cell cholesterol into the plasma-membrane compartment, since removal of sphingomyelin leads to a dramatic redistribution of cholesterol within the cell [Slotte & Bierman (1988) Biochem. J. 250, 653-658]. In the present study we examined the long-term effects of sphingomyelin degradation on cholesterol redistribution in cells and determined the reversibility of the process. In a human lung fibroblast-cell line, removal of 80% of the sphingomyelin led to a rapid and transient up-regulation (3-fold) of acyl-CoA:cholesterol acyltransferase (ACAT) activity, and also, within 30 h, to the translocation of about 50% of the cell non-esterified cholesterol from a cholesterol oxidase-susceptible compartment (i.e. the cell surface) to oxidase-resistant compartments. At 49 h after the initial sphingomyelin degradation, the cell sphingomyelin level was back to 45% of the control level, and the direction of cell cholesterol flow was toward the cell surface, although the original distribution was not achieved. In a transformed neuroblastoma cell line (SH-SY5Y), the depletion of sphingomyelin led to a similarly rapid and transient up-regulation of ACAT activity, and to the translocation of about 25% of cell-surface cholesterol into internal membranes (within 3 h). The flow of cholesterol back to the cholesterol oxidase-susceptible pool was rapid, and a pretreatment cholesterol distribution was reached within 20-49 h. Also, the resynthesis of sphingomyelin was faster in SH-SY5Y neuroblastoma cells and reached control levels within 24 h. The findings of the present study show that the cellular redistribution of cholesterol, as induced by sphingomyelin degradation, is reversible and suggest that the normalization of cellular cholesterol distribution is linked to the re-synthesis of sphingomyelin. PMID:2222406

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

PubMed Central

2011-01-01

Background The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). Conclusion These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism. PMID:22018327

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids.

PubMed

Lecker, Jaime L; Matthan, Nirupa R; Billheimer, Jeffrey T; Rader, Daniel J; Lichtenstein, Alice H

2011-10-21

The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.

The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

PubMed

Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

2016-03-01

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

A genetically informed test of cholesterol levels and self-control, depressive symptoms, antisocial behavior, and neuroticism.

PubMed

Schwartz, Joseph A; Rowland, Meghan W; Beaver, Kevin M

2014-08-01

Low cholesterol levels have been found to be associated with a wide range of behavioral problems, including violent and criminal behavior, and a wide range of psychological problems including impulsivity, depression, and other internalizing problems. The casual mechanisms underlying these associations remain largely unknown, but genetic factors may play a role in the etiology of such associations as previous research has found significant genetic influence on cholesterol levels and various deleterious behavioral and psychological outcomes. The current study addressed this existing gap in the literature by performing a genetically sensitive test of the association between cholesterol levels and various outcomes including levels of self-control, depressive symptoms, anger expression, and neuroticism. DeFries-Fulker (DF) analysis was used to analyze data from 388 twin pairs nested within the Survey of Midlife Development in the United States (MIDUS). The results of the genetically informed models revealed that high-density lipoprotein (HDL) cholesterol levels were negatively and significantly associated with depressive symptoms, had a marginally significant effect on neuroticism, and a nonsignificant effect on both anger expression and self-control. The findings may not extrapolate to the larger population of American adults since the subsample of twins with cholesterol information may not be nationally representative. Genetic influences play a significant role in the association between cholesterol levels and various deleterious outcomes and failing to control for these influences may result in model misspecification and may increase the probability of detecting a significant association when one does not actually exist. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors

PubMed Central

Pelton, Kristine; Freeman, Michael R.; Montgomery, R. Bruce

2012-01-01

Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025) Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR. PMID:22279565

MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease

PubMed Central

Yoo, Kyo-Sang; Choi, Ho Soon; Jun, Dae Won; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Lee, Kyeong Geun; Paik, Seung Sam; Kim, Yong Seok; Lee, Jin

2016-01-01

Background/Aims Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. Methods The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. Results MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. Conclusions The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression. PMID:27563024

Serum cholesterol levels of Seventh-day Adventists.

PubMed

Taylor, C B; Allen, E S; Mikkelson, B; Kang-Jey, H

1976-10-01

Serum cholesterol levels and dietary habits were surveyed in 27 male and 34 female Seventh-day Adventist. All subjects studied were lacto-ovo-vegetarians and a few consumed some meat products. Their serum cholesterol levels, significantly lower than those of the United States general population, showed no sex difference but increased with age and were higher in overweight males. Their levels, however, were much higher than those of true vegetarians which was most likely attributable to their consumption, even though to a limited acount, of dairy foods.

Measurement of Mitochondrial Cholesterol Import Using a Mitochondria-Targeted CYP11A1 Fusion Construct.

PubMed

Kennedy, Barry E; Charman, Mark; Karten, Barbara

2017-01-01

All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease. The mechanisms of mitochondrial cholesterol import are not fully elucidated yet, and may vary in different cell types and environmental conditions. Measuring cholesterol trafficking to the mitochondrial membranes is technically challenging because of its low abundance; for example, traditional pulse-chase experiments with isotope-labeled cholesterol are not feasible. Here, we describe improvements to a method first developed by the Miller group at the University of California to measure cholesterol trafficking to the inner mitochondrial membrane (IMM) through the conversion of cholesterol to pregnenolone. This method uses a mitochondria-targeted, ectopically expressed fusion construct of CYP11A1, ferredoxin reductase and ferredoxin. Pregnenolone is formed exclusively from cholesterol at the IMM, and can be analyzed with high sensitivity and specificity through ELISA or radioimmunoassay of the medium/buffer to reflect mitochondrial cholesterol import. This assay can be used to investigate the effects of genetic or pharmacological interventions on mitochondrial cholesterol import in cultured cells or isolated mitochondria.

The relationship between job stress and dyslipidemia.

PubMed

Catalina-Romero, C; Calvo, E; Sánchez-Chaparro, M A; Valdivielso, P; Sainz, J C; Cabrera, M; González-Quintela, A; Román, J

2013-03-01

To investigate whether there is an association between job stress, lipid profile and dyslipidemia diagnosis. This study used a questionnaire to evaluate job stress and lifestyle variables in 91,593 workers undergoing periodic checkups. Serum lipid levels were measured in all cases. The prevalence of job stress was 8.7% (95% CI, 8.5-8.8%). In bivariate analyses, job stress was significantly associated with previous dyslipidemia diagnosis (p < 0.001), lipid-lowering therapy (p < 0.001), and altered total-cholesterol (p = 0.001), HDL-cholesterol (p < 0.001) and LDL-cholesterol levels (p = 0.025). After adjusting for potential confounding variables, job stress was still associated with current dyslipidemia diagnosis (OR = 1.10; 95% CI, 1.04-1.17), high LDL-cholesterol (OR = 1.14; 95% CI, 1.05-1.23), low HDL-cholesterol (OR 1.08; 95% CI, 1.01-1.15), high total cholesterol/HDL-cholesterol ratio (OR 1.13; 95% CI, 1.05-1.23) and high LDL-cholesterol/HDL-cholesterol ratio (OR 1.11; 95% CI, 1.04-1.19). These results support the hypothesis of an association between job stress and lipid disturbances.

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

PubMed

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.

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

PubMed Central

2014-01-01

Background The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. Methods We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas–liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. Results The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Conclusions Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol 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. Trial registration Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117] PMID:24766766

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

PubMed

Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

2014-04-27

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol 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].

Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content.

PubMed

Lee, Do Kyung; Jang, Seok; Baek, Eun Hye; Kim, Mi Jin; Lee, Kyung Soon; Shin, Hea Soon; Chung, Myung Jun; Kim, Jin Eung; Lee, Kang Oh; Ha, Nam Joo

2009-06-11

Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether Bifidobacteria isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content. In vitro culture experiments were performed to evaluate the ability of Bifidobacterium spp. isolated from healthy Koreans (20 approximately 30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (108 approximately 109 CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks. B. longum SPM1207 reduced serum total cholesterol and LDL levels significantly (p < 0.05), and slightly increased serum HDL. B. longum SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities. Daily consumption of B. longum SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.

Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells

PubMed Central

Rosenbaum, Anton I.; Zhang, Guangtao; Warren, J. David; Maxfield, Frederick R.

2010-01-01

Niemann-Pick type C disease (NPC) is a lysosomal storage disorder causing accumulation of unesterified cholesterol in lysosomal storage organelles. Recent studies have shown that hydroxypropyl-β-cyclodextrin injections in npc1−/− mice are partially effective in treating this disease. Using cultured fibroblasts, we have investigated the cellular mechanisms responsible for reduction of cholesterol accumulation. We show that decreased levels of cholesterol accumulation are maintained for several days after removal of cyclodextrin from the culture medium. This suggests that endocytosed cyclodextrin can reduce the cholesterol storage by acting from inside endocytic organelles rather than by removing cholesterol from the plasma membrane. To test this further, we incubated both NPC1 and NPC2 mutant cells with cholesterol-loaded cyclodextrin for 1 h, followed by chase in serum-containing medium. Although the cholesterol content of the treated cells increased after the 1-h incubation, the cholesterol levels in the storage organelles were later reduced significantly. We covalently coupled cyclodextrin to fluorescent dextran polymers. These cyclodextrin–dextran conjugates were delivered to cholesterol-enriched lysosomal storage organelles and were effective at reducing the cholesterol accumulation. We demonstrate that methyl-β-cyclodextrin is more potent than hydroxypropyl-β-cyclodextrin in reducing both cholesterol and bis(monoacylglycerol) phosphate accumulation in NPC mutant fibroblasts. Brief treatment of cells with cyclodextrins causes an increase in cholesterol esterification by acyl CoA:cholesterol acyl transferase, indicating increased cholesterol delivery to the endoplasmic reticulum. These findings suggest that cyclodextrin-mediated enhanced cholesterol transport from the endocytic system can reduce cholesterol accumulation in cells with defects in either NPC1 or NPC2. PMID:20212119

Association between cholesterol plasma levels and craving among heroin users.

PubMed

Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

2012-12-01

Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P < 0.01, and r = -0.36, P < 0.01, respectively) and after controlling for the effects of potential confounders (β = -0.38, P < 0.01, and β = -0.42, P < 0.01, respectively). Cholesterol could be associated with the cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease.

PubMed

Jung, Ji-Hye; Kim, Hyun-Sook

2013-10-01

Non-alcoholic fatty liver disease (NAFLD) is defined as excess of fat in the liver. We investigated the effects of black soybean on the cholesterol metabolism and insulin resistance of mice fed high cholesterol/fat diets. Mice were randomly allocated into four groups that were fed different diets: the normal cholesterol/fat diet; high cholesterol/fat diets (HCD); and HCD with 1%, and 4% black soybean powder (1B-HCD, and 4B-HCD). Liver total cholesterol and triglyceride concentrations were significantly lower in the black soybean-supplemented groups than that in the HCD group. PCR revealed significantly lower hepatic SREBP2 and HMG-CoA reductase mRNA levels of black soybean-supplemented mice. Real-time PCR revealed significantly higher hepatic ABCA1 mRNA level of black soybean-supplemented mice, which may increase cholesterol efflux. Liver bile acids concentration was significantly high in the 4B-HCD group. Black soybean stimulated secretion of adiponectin, activation of pAMPK, and eliminated free fatty acids in the liver. Black soybean supplementation decreased MDA and nitrate level. The activities of SOD, catalase, and GPx were restored by black soybean supplementation. Our data strongly indicate that black soybean influences the balance between oxidative and antioxidative stress. We suggest that black soybean improves cholesterol metabolism, insulin resistance, and alleviates oxidative damage in NAFLD. Published by Elsevier Ltd.

Puerarin promotes ABCA1-mediated cholesterol efflux and decreases cellular lipid accumulation in THP-1 macrophages.

PubMed

Li, Cong-Hui; Gong, Duo; Chen, Ling-Yan; Zhang, Min; Xia, Xiao-Dan; Cheng, Hai-Peng; Huang, Chong; Zhao, Zhen-Wang; Zheng, Xi-Long; Tang, Xiao-Er; Tang, Chao-Ke

2017-09-15

It was reported that puerarin decreases the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and increases high-density lipoprotein cholesterol (HDL-C) level, but the underlying mechanism is unclear. This study was designed to determine whether puerarin decreased lipid accumulation via up-regulation of ABCA1-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. Our results showed that puerarin significantly promoted the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor-alpha (LXR-α) pathway and decreased cellular lipid accumulation in human THP-1 macrophage-derived foam cells. The miR-7 directly targeted 3' untranslated region of STK11 (Serine/Threonine Kinase 11), which activated the AMPK pathway. Transfection with miR-7 mimic significantly reduced STK11 expression in puerarin-treated macrophages, decreased the phosphorylation of AMPK, down-regulated the expression of the PPARγ-LXR-α-ABCA1 expression. Additionally, treatment with miR-7 decreased cholesterol efflux and increased cholesterol levels in THP-1 macrophage-derived foam cells. Our study demonstrates that puerarin promotes ABCA1-mediated cholesterol efflux and decreases intracellular cholesterol levels through the pathway involving miR-7, STK11, and the AMPK-PPARγ-LXR-α-ABCA1 cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitamin D Levels and Lipid Response to Atorvastatin

PubMed Central

Pérez-Castrillón, José Luis; Abad Manteca, Laura; Vega, Gemma; del Pino Montes, Javier; de Luis, Daniel; Dueňas Laita, Antonio

2010-01-01

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45 ± mg/dL); whereas patients with insufficient (30–50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction. PMID:20016682

LDL-C levels in older people: Cholesterol homeostasis and the free radical theory of ageing converge.

PubMed

Mc Auley, Mark T; Mooney, Kathleen M

2017-07-01

The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations. We hypothesize that the free radical theory of ageing (FRTA) together with disrupted cholesterol homeostasis can account for these observations. Based on this hypothesis, dysregulated hepatic cholesterol homeostasis in older people is characterised by two distinct metabolic states. The first state accounts for an older person who has elevated plasma LDL-C. This state is underpinned by the FRTA which suggests there is a decrease in cellular antioxidant capacity with age. This deficiency enables hepatic reactive oxidative species (ROS) to induce the total activation of HMG-CoA reductase, the key rate limiting enzyme in cholesterol biosynthesis. An increase in cholesterol synthesis elicits a corresponding rise in LDL-C, due to the downregulation of LDL receptor synthesis, and increased production of very low density lipoprotein cholesterol (VLDL-C). In the second state of dysregulation, ROS also trigger the total activation of HMG-CoA reductase. However, due to an age associated decrease in the activity of cholesterol-esterifying enzyme, acyl CoA: cholesterol acyltransferase, there is restricted conversion of excess free cholesterol (FC) to cholesterol esters. Consequently, the secretion of VLDL-C drops, and there is a corresponding decrease in LDL-C. As intracellular levels of FC accumulate, this state progresses to a pathophysiological condition akin to nonalcoholic fatty liver disease. It is our conjecture this deleterious state has the potential to account for the inverse association between LDL-C level and CVD risk observed in older people. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cholesterol and Women's Health

MedlinePlus

... having a high LDL cholesterol level lead to cardiovascular disease? • Besides abnormal cholesterol, what are other risk factors for cardiovascular disease? • What are some risk factors for cardiovascular disease ...

How cells handle cholesterol.

PubMed

Simons, K; Ikonen, E

2000-12-01

Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Recent advances suggest that cholesterol exerts many of its actions mainly by maintaining sphingolipid rafts in a functional state. How rafts contribute to cholesterol metabolism and transport in the cell is still an open issue. It has long been known that cellular cholesterol levels are precisely controlled by biosynthesis, efflux from cells, and influx of lipoprotein cholesterol into cells. The regulation of cholesterol homeostasis is now receiving a new focus, and this changed perspective may throw light on diseases caused by cholesterol excess, the prime example being atherosclerosis.

Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

PubMed

Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

2011-06-01

Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids reduce blood cholesterol concentrations and aortic cholesterol accumulation in hamsters.

PubMed

Wilson, Thomas A; Kritchevsky, David; Kotyla, Timothy; Nicolosi, Robert J

2006-03-01

The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%) had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.

Elastic Multi-scale Mechanisms: Computation and Biological Evolution.

PubMed

Diaz Ochoa, Juan G

2018-01-01

Explanations based on low-level interacting elements are valuable and powerful since they contribute to identify the key mechanisms of biological functions. However, many dynamic systems based on low-level interacting elements with unambiguous, finite, and complete information of initial states generate future states that cannot be predicted, implying an increase of complexity and open-ended evolution. Such systems are like Turing machines, that overlap with dynamical systems that cannot halt. We argue that organisms find halting conditions by distorting these mechanisms, creating conditions for a constant creativity that drives evolution. We introduce a modulus of elasticity to measure the changes in these mechanisms in response to changes in the computed environment. We test this concept in a population of predators and predated cells with chemotactic mechanisms and demonstrate how the selection of a given mechanism depends on the entire population. We finally explore this concept in different frameworks and postulate that the identification of predictive mechanisms is only successful with small elasticity modulus.

Degradation of Leakage Currents in Solid Tantalum Capacitors Under Steady-State Bias Conditions

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander A.

2010-01-01

Degradation of leakage currents in various types of solid tantalum capacitors under steady-state bias conditions was investigated at temperatures from 105 oC to 170 oC and voltages up to two times the rated voltage. Variations of leakage currents with time under highly accelerated life testing (HALT) and annealing, thermally stimulated depolarization currents, and I-V characteristics were measured to understand the conduction mechanism and the reason for current degradation. During HALT the currents increase gradually up to three orders of magnitude in some cases, and then stabilize with time. This degradation is reversible and annealing can restore the initial levels of leakage currents. The results are attributed to migration of positively charged oxygen vacancies in tantalum pentoxide films that diminish the Schottky barrier at the MnO2/Ta2O5 interface and increase electron injection. A simple model allows for estimation of concentration and mobility of oxygen vacancies based on the level of current degradation.

[Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats].

PubMed

Cárdenas Medellín, M L; Serna Saldívar, S O; Velazco de la Garza, J

1998-12-01

Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P < 0.05) when compared with counterparts fed 6% nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals.

Detection of virgin coconut oil adulteration with animal fats using quantitative cholesterol by GC × GC-TOF/MS analysis.

PubMed

Xu, Baocheng; Li, Peiwu; Ma, Fei; Wang, Xiuping; Matthäus, Bertrand; Chen, Ran; Yang, Qingqing; Zhang, Wen; Zhang, Qi

2015-07-01

A new method based on the cholesterol level was developed to detect the presence of animal fats in virgin coconut oil (VCO). In this study, the sterols in VCO and animal fats was separated using conventional one-dimensional gas chromatography (1D GC) and comprehensive two-dimensional gas chromatography (GC×GC). Compared with 1D GC, the GC×GC system could obtain a complete baseline separation of the sterol trimethylsilyl ethers derived from cholesterol and cholestanol, so that the cholesterol content in pure VCO and false VCO adulterated with animal fats could be accurately determined. Cholesterol, a main sterol found in animal fats, represented less than 5mg/kg of VCO. The study demonstrated that the determination of the cholesterol level in VCO could be used for reliable detection of the presence of lard, chicken fat, mutton tallow, beef tallow, or their mixture in VCO at a level as little as 0.25%. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice.

PubMed

Wang, Li; Zhang, Xue Tong; Zhang, Hai Yan; Yao, Hui Yuan; Zhang, Hui

2010-08-09

To investigate the hypoglycemic effects of Vaccinium bracteatum Thunb. leaves (VBTL) extract in streptozotocin-induced diabetic mice. After administration of VBTL extract for 4 weeks, the body weight, organ weight, blood glucose (BG), insulin and plasma lipid levels of streptozotocin-induced diabetic mice were measured. Body weights of diabetic mice treated with VBTL extract were partly recovered. The BG levels of AEG (diabetic mice treated with VBTL aqueous extract) were reduced to 91.52 and 85.82% at week 2 and week 4, respectively (P<0.05), while those of EEG (diabetic mice treated with VBTL ethanolic extract) were reduced slightly (P>0.05). The insulin levels of AEG and EEG were obviously higher (P<0.05) than those of MC (diabetic mice in model control group). Comparing with MC, AEG and EEG had significantly lower (P<0.05) TC or TG levels and similar HDL-cholesterol or LDL-cholesterol levels. In comparison with non-diabetic control mice, AEG had similar plasma lipid levels except higher LDL-cholesterol level, while EEG had higher TC, TG and LDL-cholesterol levels and lower HDL-cholesterol levels. Both aqueous and ethanolic extract of VBTL possess a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet

PubMed Central

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

Acidic polysaccharide extracts from Gastrodia Rhizomes suppress the atherosclerosis risk index through inhibition of the serum cholesterol composition in Sprague Dawley rats fed a high-fat diet.

PubMed

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels.

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

PubMed Central

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-01-01

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. PMID:19638223

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet.

PubMed

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-07-28

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.

Serum cholesterol reduction by feeding a high-cholesterol diet containing a lower-molecular-weight polyphenol fraction from peanut skin.

PubMed

Tamura, Tomoko; Inoue, Naoko; Shimizu-Ibuka, Akiko; Tadaishi, Miki; Takita, Toshichika; Arai, Soichi; Mura, Kiyoshi

2012-01-01

Feeding a high-cholesterol diet with a water-soluble peanut skin polyphenol fraction to rats reduced their plasma cholesterol level, with an increase in fecal cholesterol excretion. The hypocholesterolemic effect was greater with the lower-molecular-weight rather than higher-molecular-weight polyphenol fraction. This effect was possibly due to some oligomeric polyphenols which reduced the solubility of dietary cholesterol in intestinal bile acid-emulsified micelles.

The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation.

PubMed

Sharma, Hari; Zhang, Xiaoying; Dwivedi, Chandradhar

2010-04-01

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.

Serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who take hydroxymethylglutaryl-CoA reductase inhibitors, vitamin B6, and folic acid.

PubMed

Shojaei, Mir Hatef; Djalali, Mamhmoud; Siassi, Fereydoun; Khatami, Mohammad Reza; Boroumand, Mohammad Ali; Eshragian, Mohammad Reza

2009-07-01

High serum levels of lipoprotein(a) and homocysteine are risk factors of cardiovascular disease which are prevalent in patients on hemodialysis. Controversy exists about the effects of hydroxymethylglutaryl-CoA reductase inhibitors on serum lipoprotein(a) levels in patients on hemodialysis. Also, deficiency of some water soluble vitamins and administration of statins may raise serum levels of homocysteine in these patients. This study was designed to investigate serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who were taking a statin, vitamin B6, and folic acid. We investigated on 152 patients with maintenance hemodialysis who were taking atorvastatin or lovastatin, vitamin B6, and folic acid for at least 6 months. Their serum levels were obtained to measure lipoprotein(a) and homocysteine levels, as well as triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The mean serum values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and triglyceride were significantly less than the maximum reference values (P < .001). The mean serum level of lipoprotein(a) was also less than the reference value (P = .009), but homocysteine level was 33% higher on average than the reference value (P < .001). Our study demonstrated that in our patients on hemodialysis, the mean serum level of homocysteine was about 30% higher than the reference value although they were receiving vitamin B6 and folic acid. Hence, they were still exposed to the risk of cardiovascular disease.

Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study.

PubMed

di Giuseppe, Romina; Pechlivanis, Sonali; Fisher, Eva; Arregui, Maria; Weikert, Beate; Knüppel, Sven; Buijsse, Brian; Fritsche, Andreas; Willich, Stefan N; Joost, Hans-Georg; Boeing, Heiner; Moebus, Susanne; Weikert, Cornelia

2013-01-29

The microsomal triglyceride transfer protein (MTTP) is encoded by the MTTP gene that is regulated by cholesterol in humans. Previous studies investigating the effect of MTTP on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in MTTP alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels. The -164T > C polymorphism was genotyped in a case-cohort study (193 incident myocardial infarction (MI) and 131 incident ischemic stroke (IS) cases and 1 978 non-cases) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, comprising 27 548 middle-aged subjects. The Heinz Nixdorf Recall study (30 CVD cases and 1 188 controls) was used to replicate our findings. Genotype frequencies were not different between CVD and CVD free subjects (P = 0.79). We observed an interaction between the -164T > C polymorphism and total cholesterol levels in relation to future CVD. Corresponding stratified analyses showed a significant increased risk of CVD (HR(additve) = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HR(additive) was 1.06, 95% CI: 0.33 to 3.40 for individuals in the Heinz Nixdorf Recall study. A borderline significant decrease in CVD risk was observed in subjects with cholesterol levels ≥ 200 mg/dL (HR(additve) = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HR(additve) = 0.60, 95% CI: 0.29 to 1.25). Our study suggests an interaction between MTTP -164T > C functional polymorphism with total cholesterol levels. Thereby risk allele carriers with low cholesterol levels may be predisposed to an increased risk of developing CVD, which seems to be abolished among risk allele carriers with high cholesterol levels.

Beneficial effects of cytokine induced hyperlipidemia.

PubMed

Feingold, K R; Hardardóttir, I; Grunfeld, C

1998-01-01

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.

The 32-year relationship between cholesterol and dementia from midlife to late life.

PubMed

Mielke, M M; Zandi, P P; Shao, H; Waern, M; Östling, S; Guo, X; Björkelund, C; Lissner, L; Skoog, I; Gustafson, D R

2010-11-23

Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38-60 years, was initiated in 1968-1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974-1975, 1980-1981, 1992-1993, and 2000-2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000-2001 examination. Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94-8.43) among those who survived to and participated in the 2000-2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22-4.58). These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.

The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

NASA Astrophysics Data System (ADS)

Kurniati, Neng Fisheri; Permatasari, Anita

2015-09-01

Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1.

PubMed

Lv, Yun-Cheng; Tang, Yan-Yan; Peng, Juan; Zhao, Guo-Jun; Yang, Jing; Yao, Feng; Ouyang, Xin-Ping; He, Ping-Ping; Xie, Wei; Tan, Yu-Lin; Zhang, Min; Liu, Dan; Tang, Deng-Pei; Cayabyab, Francisco S; Zheng, Xi-Long; Zhang, Da-Wei; Tian, Guo-Ping; Tang, Chao-Ke

2014-09-01

Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects. MiR-19b promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ABCA1. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of VCO and olive oil on HDL, LDL, and cholesterol level of hyperglycemic Rattus Rattus Norvegicus

NASA Astrophysics Data System (ADS)

Yusuf Wachidah Yuiwarti, Enny; Rini Saraswati, Tyas; Kusdiyantini, Endang

2018-05-01

Virgin coconut oil (VCO) and olive oil are edible oil containing an antioxidant that can prevent free radicals in Rattus rattus norvegicus hypoglycemic due to the damage of pancreatic beta cell after alloxan injection. Virgin coconut oil and olive oil are fatty acids when being consumed will affect lipid metabolism particularly HDL, LDL and cholesterol in serum. This research aims to determine the effect of VCO and Olive oil on cholesterol levels in hyperglycemic rats. Research materials were twenty male Rattus rattus norvegicus. Randomized Factorial Design was used in four treatment groups including P1(control), P2 (mice injected with alloxan), P3 (mice injected with alloxan plus 0.1 ml/BW of each VCO and vitamin E) and P4 (mice injected with alloxan plus 0.1 ml/BW of each olive oil and vitamin E. Each treatment was replicated 5 times. Feed and water were provided adlibitum for four weeks. The result showed that there was no significant difference in the level of HDL serum across the treatments, but P4 had a significantly higher LDL than the other treatments. Moreover, total cholesterol was significantly increased in P4 compared to the other groups. It can be concluded that olive oil could increase the level of cholesterol and LDL in serum, while VCO did not increase the level of cholesterol and LDL so VCO more potential to maintain cholesterol in hyperglycemic Rattus rattus norvegicus.

Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba.

PubMed

Hall, K; Murrell, J; Ogunniyi, A; Deeg, M; Baiyewu, O; Gao, S; Gureje, O; Dickens, J; Evans, R; Smith-Gamble, V; Unverzagt, F W; Shen, J; Hendrie, H

2006-01-24

To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Cholesterol, APOE genotype, and Alzheimer disease

PubMed Central

Hall, K.; Murrell, J.; Ogunniyi, A.; Deeg, M.; Baiyewu, O.; Gao, S.; Gureje, O.; Dickens, J.; Evans, R.; Smith-Gamble, V.; Unverzagt, F.W.; Shen, J.; Hendrie, H.

2010-01-01

Objective To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Methods Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p = 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4. Conclusions There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies. PMID:16434658

Anti-TNFα therapy transiently improves high density lipoprotein cholesterol levels and microvascular endothelial function in patients with rheumatoid arthritis: a Pilot Study

PubMed Central

2012-01-01

Background Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function. Methods Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment. Results Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks. Conclusion Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function. PMID:22824166

Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat.

PubMed Central

Ventura, M A; Woollett, L A; Spady, D K

1989-01-01

These studies were undertaken to examine the effect of fish oil, safflower oil, and hydrogenated coconut oil on the major processes that determine the concentration of low density lipoprotein (LDL) in plasma, i.e., the rate of LDL production and the rates of receptor-dependent and receptor-independent LDL uptake in the various organs of the body. When fed at the 20% level, fish oil reduced plasma LDL-cholesterol levels by 38% primarily by increasing LDL receptor activity in the liver. Dietary safflower oil also increased hepatic LDL receptor activity; however, since the rate of LDL production also increased, plasma LDL-cholesterol levels remained essentially unchanged. Hydrogenated coconut oil had no effect on LDL receptor activity but increased the rate of LDL-cholesterol production causing plasma LDL-cholesterol levels to increase 46%. Dietary fish oil had no effect on the receptor-dependent transport of asialofetuin by the liver, suggesting that the effect of fish oil on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physical properties of hepatic membranes. Finally, dietary fish oil increased hepatic cholesteryl ester levels and suppressed hepatic cholesterol synthesis rates, suggesting that the up-regulation of hepatic LDL receptor activity in these animals was not simply a response to diminished cholesterol availability in the liver. PMID:2760200

Community cholesterol screening. Impact of labeling on participant behavior.

PubMed

Gordon, R L; Klag, M J; Whelton, P K

1990-09-01

To investigate the effect of screening for an elevated cholesterol level and compliance with follow-up recommendations, we surveyed 375 participants in a free screening program at a shopping mall walk-in clinic. One hundred thirty-nine participants (37%) had desirable (less than 5.17 mmol/L [less than 200 mg/dL]), 135 (36%) had borderline (5.17 to 6.18 mmol/L [200 to 239 mg/dL]), and 101 (27%) had high (greater than 6.18 mmol/L [greater than 239 mg/dL]) cholesterol levels. Persons in the borderline and high categories were instructed to see their physicians within 2 months for confirmation of their levels. Of the 338 (90%) who responded to a follow-up questionnaire at 3 months, 8 (7%) in the desirable, 23 (22%) in the borderline, and 44 (50%) in the high group had been to see physicians concerning their cholesterol levels since the screening. In multiple logistic regression analyses only cholesterol category at time of screening, current use of antihypertensive drugs, history of coronary heart disease, and history of a high cholesterol level were associated with physician follow-up. Our results suggest that labeling persons as being at high rather than borderline risk results in greater physician follow-up.

Achieving Zero Net Migration.

ERIC Educational Resources Information Center

Mann, Donald

1984-01-01

Unemployment in the United States can only be made worse by continued high levels of legal immigration. Especially serious is the threat from Latin America. We must help developing countries halt their population growth and impose a ceiling of 100,000 a year for total immigration to the United States. (RM)

Association between high-density lipoprotein cholesterol level and pulmonary function in healthy Korean adolescents: the JS high school study.

PubMed

Park, Ji Hye; Mun, Seyeon; Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2017-12-11

Accumulating evidence suggests that high-density lipoprotein (HDL) cholesterol is associated with pulmonary function and pulmonary disorders. The aim of this study was to evaluate the association between HDL cholesterol and pulmonary function in healthy adolescents. This cross-sectional study was based on data collected for the JS High School study. The analysis included 644 adolescents (318 male and 326 female) aged 15-16 years old and free from asthma or chronic obstructive pulmonary disease. Fasting blood samples were collected for hematologic and biochemical assessment. Forced vital capacity volume (FVC) and forced expiratory volume in the 1 s (FEV1) were measured using dry-rolling-seal spirometry. The associations between HDL cholesterol and pulmonary function were analyzed using multiple linear regression models. Among male adolescents, an increase of 1.0 mg/dL in HDL cholesterol was associated with 10 mL decrease in FVC (p = 0.013) and FEV1 (p = 0.013) after adjusting for age, height, weight, alcohol drinking, smoking, physical activity, systolic blood pressure, total cholesterol, triglyceride, and monthly household income. Percent predicted values of FVC (p = 0.036) and FEV1 (p = 0.017) were also inversely associated with HDL cholesterol. However, among female adolescents, HDL cholesterol level was not significantly associated with absolute or percent predictive value of FVC and FEV1. Higher HDL cholesterol level may be associated with decreased pulmonary function among healthy male adolescents. The sex differences observed in the association between HDL cholesterol and pulmonary function need further investigation.

The good and the bad: what researchers have learned about dietary cholesterol, lipid management and cardiovascular disease risk since the Harvard Egg Study.

PubMed

Constance, C

2009-10-01

The prevalence of cardiovascular diseases, while lower than it once was, remains a significant health consideration. To review the evolving evidence with respect to what role various factors play in the aetiology of coronary heart disease (CHD). While total cholesterol and low-density lipoprotein cholesterol (LDL-C) were previously believed to play central roles, it has now become clear that neither in isolation is highly significant. For example, some people with very high LDL-C levels do not develop CHD, while others with very low LDL-C levels do. Furthermore, there is a difference between dietary cholesterol and serum cholesterol. Dietary cholesterol, which is found in animal-based foods, raises blood cholesterol in only approximately one-third of people. Conversely, intake of saturated fatty acids and trans fatty acids can result in dyslipidaemia. Furthermore, obesity--particularly abdominal obesity--and metabolic syndrome both are strong independent risk factors for development of cardiovascular disease. Statin therapy and a diet comprising a portfolio of plant sterols and viscous fibres can both significantly reduce LDL-C levels and C-reactive protein. The latter is a key marker of inflammation and of elevated risk for cardiovascular disease.

Modulation of cholesterol levels in broiler meat by dietary garlic and copper.

PubMed

Konjufca, V H; Pesti, G M; Bakalli, R I

1997-09-01

Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2. Once the dose-response relationship was established, 3% garlic powder or 63 or 180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were observed in garlic-supplemented birds. Feeding either garlic powder or copper (63 and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol. Differences were significant at P < 0.05 in at least one experiment. 3-Hydroxy-3-methylglutaryl reductase activity was decreased due to dietary garlic (P = 0.0369), but not by pharmacological levels of dietary copper (P = 0.982). The activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035). Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase activity (P = 0.024 and P = 0.022, respectively). The results of these trials confirm the findings that garlic and copper alter lipid and cholesterol metabolism. However, they do not work by the same mechanism. Feeding dietary garlic or copper for 21 d reduced cholesterol levels of broiler meat without altering growth of the chickens or feed efficiency.

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects.

PubMed

Aptekmann, Nancy P; Cesar, Thais B

2013-08-06

This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet.

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects

PubMed Central

2013-01-01

Background This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. Methods The sample consisted of 103 men (18–66 y) and 26 women (18–65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Results Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (−11%, p <0.001), LDL-cholesterol (−18%, p < 0.001), apolipoprotein B (apo B) (−12%, p < 0.01) and LDL/HDL ratio (−12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (−5%, p <0.02), LDL-cholesterol (−12%, p <0.03), apolipoprotein B (−12%, p <0.01) and LDL/HDL ratio (−16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Conclusion Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. PMID:23919812

Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane.

PubMed

Rabani, Vahideh; Montange, Damien; Meneveau, Nicolas; Davani, Siamak

2017-10-11

Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treated by ticagrelor, or both. In ADP-stimulated and ticagrelor-treated groups, we found a decreased level of cholesterol in raft fractions of platelet plasma membrane compared to the control group. In addition, the peak of cholesterol in different experimental groups changed its localization on membrane fractions. In the control group, it was situated on fraction 2, while in ADP-stimulated platelets, it was located in fractions 3 to 5, and in fraction 4 in ticagrelor-treated group. The proteins studied also showed changes in their level of expression and localization in fractions of plasma membrane. Cholesterol levels of plasma membranes have a direct role in the organization of platelet membranes and could be modified by stimulation or drug treatment. Since ticagrelor and ADP both changed lipid composition and protein profile, investigating the lipid and protein composition of platelet membranes is of considerable importance as a focus for further research in anti-platelet management.

Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

PubMed

Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

2015-02-13

Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na⁺ loss.

PubMed

Oliveira, Fabiana S T; Vieira-Filho, Leucio D; Cabral, Edjair V; Sampaio, Luzia S; Silva, Paulo A; Carvalho, Vera C O; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Lima, Vera L M; Paixão, Ana D O

2013-04-01

It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats. Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration. Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls. Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.

Effects of Lycopene on the Initial State of Atherosclerosis in New Zealand White (NZW) Rabbits

PubMed Central

Lorenz, Mario; Fechner, Mandy; Kalkowski, Janine; Fröhlich, Kati; Trautmann, Anne; Böhm, Volker; Liebisch, Gerhard; Lehneis, Stefan; Schmitz, Gerd; Ludwig, Antje; Baumann, Gert; Stangl, Karl; Stangl, Verena

2012-01-01

Background Lycopene is the main carotenoid in tomatoes, where it is found in high concentrations. Strong epidemiological evidence suggests that lycopene may provide protection against cardiovascular diseases. We therefore studied the effects of lycopene on diet-induced increase in serum lipid levels and the initiation of atherosclerosis in New Zealand White (NZW) rabbits. Methodology/Principal Findings The animals, divided into four groups of 9 animals each, were fed either a standard diet, a high-cholesterol diet containing 0.5% cholesterol, a high-cholesterol diet containing placebo beadlets, or a high-cholesterol diet plus 5 mg/kg body weight/day of lycopene (in the form of lycopene beadlets), for a period of 4 weeks. We found significantly elevated lycopene plasma levels in the animal group treated with lycopene beadlets. Compared to the high-cholesterol and the placebo group, this was associated with a significant reduction of 50% in total cholesterol and LDL cholesterol serum levels in the lycopene group. The amount of cholesteryl ester in the aorta was significantly decreased by lycopene. However, we did not observe a significant decrease in the extent of aortic surface lipid accumulation in the lycopene group. In addition, no differences in the intima-media thickness among groups were observed. Endothelial-dependent and endothelial-independent vasodilation in isolated rabbit aortic and carotid rings did not differ among any of the animal groups. Conclusions Lycopene supplementation for 4 weeks increased lycopene plasma levels in the animals. Although we found strongly reduced total and LDL cholesterol serum levels as well as significantly lower amounts of cholesteryl ester in the aortae in the lycopene-treated group, no significant differences in initial lesions in the aortae were detected. PMID:22295112

Zonal differences in the distribution and morphology of lipid droplets using 4-amino-pyrazolo-(3,4 d) pyrimidine to lower cholesterol level in the rat adrenal.

PubMed

Szabó, D; Somogyi, J; Acs, Z; Mihály, K

1980-01-01

The effect of reduced blood and adrenal cholesterol levels on adrenocortical lipid droplets have been examined by treating adult rats with 4-amino-pyrazolo-(3,4 d) pyrimidine (4-APP), a drug that inhibits hepatic secretion of lipoproteins. Lowering the blood cholesterol level and the cholesterol content of the adrenals was associated with a marked reduction in the lipid droplets and with a simultaneous increase in their electron density in the inner cortical zones. In the zona glomerulosa cells, no perceptible differences were found in the quantity and morphology of lipid droplets. These data suggest that reduced blood and adrenal cholesterol levels do not affect lipids located in the zona glomerulosa and in the inner cortical zones in the same way, probably due to differences in their intracellular lipid dynamism. Noteworthy, that in spite of the marked lipid depletion, the adrenal glands retained their responsiveness to ACTH stimulation.

Effects of Diet High in Palmitoleic Acid on Serum Lipid Levels and Metabolism

DTIC Science & Technology

2000-07-01

cholesterol , high - density a typical American diet. lipoprotein cholesterol , and triglyceride ...group imbalance resulting from density lipoprotein ( HDL ) cholesterol , and triglyceride dropouts or exclusions during the run-in or early in the levels...Circulation 1997;95:69-75. 15. Austin MA, Rodriguez BL, McKnight B, JD Curb. Low- density lipoprotein (LDL) particle size and plasma triglyceride ( TG

The effects of vitamine C on lipid metabolism.

PubMed

Kotzé, J P

1975-09-20

Evidence is presented showing that vitamin C had definite effects on lipid metabolism. The stress of captivity on free-living baboons causes a decrease in serum vitamin C levels and an increase in serum cholesterol levels. Increased dietary intake of vitamin C during the initial stages of captivity significantly decreases the serum cholesterol values. Dietary vitamin C stimulates the synthesis of cholesterol from 14C-labelled acetate and mevalonate in baboon liver homogenates and increases the turnover rate of the cholesterol body pool. Vitamin C inhibits baboon cardiac lipoprotein lipase activity.

Serum cholesterol and triglyceride concentrations in diabetic patients with subclinical hypothyroidism.

PubMed

Díez, Juan J; Iglesias, Pedro

2014-10-01

To assess whether subclinical hypothyroidism is associated to elevations in serum cholesterol and triglyceride levels in patients with type 2 diabetes. From a total population of 1,112 patients with type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a group of 325 patients with normal thyroid function and another group of 29 patients with subclinical hypothyroidism were selected. No patient had known dyslipidemia or was taking lipid lowering medication. Patients with subclinical hypothyroidism had serum levels of total cholesterol (4.88 ± 0.74 mmol/L), HDL cholesterol (1.37 ± 0.34 mmol/L), LDL cholesterol (2.94 ± 0.58 mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly differ from those found in euthyroid patients (4.79 ± 0.83, 1.33 ± 0.36, 2.87 ± 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression analysis showed no association between TSH and serum lipid levels. These results suggest that, in our population, there are no significant differences in serum cholesterol and triglyceride levels between diabetic patients with normal and reduced thyroid function. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Ursodiol

MedlinePlus

... gallbladder. It works by decreasing the production of cholesterol and by dissolving the cholesterol in bile so that it cannot form stones. ... Atromid-S), colestipol (Colestid), medications that lower lipid or cholesterol levels, medications that contain estrogen (including birth control ...

Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.

PubMed

Abdelmaksoud, Abdallah A; Girerd, Philippe H; Garcia, Erin M; Brooks, J Paul; Leftwich, Lauren M; Sheth, Nihar U; Bradley, Steven P; Serrano, Myrna G; Fettweis, Jennifer M; Huang, Bernice; Strauss, Jerome F; Buck, Gregory A; Jefferson, Kimberly K

2017-01-01

Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome. To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity. The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol. In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.

Do perfluoroalkyl substances affect metabolic function and plasma lipids?--Analysis of the 2007-2009, Canadian Health Measures Survey (CHMS) Cycle 1.

PubMed

Fisher, Mandy; Arbuckle, Tye E; Wade, Mike; Haines, Douglas A

2013-02-01

Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism. The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels. Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007-2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models. We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters. This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON-HDL, TC/HDL ratio). Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake

PubMed Central

Yang, Muhua; Liu, Weidong; Pellicane, Christina; Sahyoun, Christine; Joseph, Biny K.; Gallo-Ebert, Christina; Donigan, Melissa; Pandya, Devanshi; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

2014-01-01

Dysregulation of cholesterol homeostasis is associated with various metabolic diseases, including atherosclerosis and type 2 diabetes. The sterol response element binding protein (SREBP)-2 transcription factor induces the expression of genes involved in de novo cholesterol biosynthesis and low density lipoprotein (LDL) uptake, thus it plays a crucial role in maintaining cholesterol homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells repressed SREBP-2 expression and protein level. miR-185-directed inhibition caused decreased SREBP-2-dependent gene expression, LDL uptake, and HMG-CoA reductase activity. In addition, we found that miR-185 expression was tightly regulated by SREBP-1c, through its binding to a single sterol response element in the miR-185 promoter. Moreover, we found that miR-185 expression levels were elevated in mice fed a high-fat diet, and this increase correlated with an increase in total cholesterol level and a decrease in SREBP-2 expression and protein. Finally, we found that individuals with high cholesterol had a 5-fold increase in serum miR-185 expression compared with control individuals. Thus, miR-185 controls cholesterol homeostasis through regulating SREBP-2 expression and activity. In turn, SREBP-1c regulates miR-185 expression through a complex cholesterol-responsive feedback loop. Thus, a novel axis regulating cholesterol homeostasis exists that exploits miR-185-dependent regulation of SREBP-2 and requires SREBP-1c for function. PMID:24296663

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells

PubMed Central

2014-01-01

Background Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). Methods MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. Results We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Conclusion Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment. PMID:25401046

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells.

PubMed

Benakanakere, Indira; Johnson, Tyler; Sleightholm, Richard; Villeda, Virgilio; Arya, Monika; Bobba, Ravi; Freter, Carl; Huang, Chunfa

2014-01-01

Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment.

Activated Charcoal

MedlinePlus

... is used to treat poisonings, reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile ... lower cholesterol levels in the blood. Decreasing gas (flatulence). Some studies show that activated charcoal is effective ...

Relationship of drinking water disinfectants to plasma cholesterol and thyroid hormone levels in experimental studies.

PubMed Central

Revis, N W; McCauley, P; Bull, R; Holdsworth, G

1986-01-01

The effects of drinking water containing 2 or 15 ppm chlorine (pH 6.5 and 8.5), chlorine dioxide, and monochloramine on thyroid function and plasma cholesterol were studied because previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels, as compared to controls, were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm (the exception was chlorine at pH 6.5) for 3 months. In most of the treatment groups, T4 levels were significantly lower following the exposure to drinking water containing the 2 ppm dose. Increases in plasma cholesterol were frequently observed in the groups with lower T4 levels. This association was most evident in pigeons fed the high-cholesterol diet and exposed to these disinfectants at a dose of 15 ppm. For example, after 3 months of exposure to deionized water or water containing 15 ppm monochloramine, plasma cholesterol was 1266 +/- 172 and 2049 +/- 212 mg/dl, respectively, a difference of 783 mg/dl. The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. We suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract. PMID:3456597

Identification of a novel polymorphism in X-linked sterol-4-alpha-carboxylate 3-dehydrogenase (Nsdhl) associated with reduced high-density lipoprotein cholesterol levels in I/LnJ mice.

PubMed

Bautz, David J; Broman, Karl W; Threadgill, David W

2013-10-03

Loci controlling plasma lipid concentrations were identified by performing a quantitative trait locus analysis on genotypes from 233 mice from a F2 cross between KK/HlJ and I/LnJ, two strains known to differ in their high-density lipoprotein (HDL) cholesterol levels. When fed a standard diet, HDL cholesterol concentration was affected by two significant loci, the Apoa2 locus on Chromosome (Chr) 1 and a novel locus on Chr X, along with one suggestive locus on Chr 6. Non-HDL concentration also was affected by loci on Chr 1 and X along with a suggestive locus on Chr 3. Additional loci that may be sex-specific were identified for HDL cholesterol on Chr 2, 3, and 4 and for non-HDL cholesterol on Chr 5, 7, and 14. Further investigation into the potential causative gene on Chr X for reduced HDL cholesterol levels revealed a novel, I/LnJ-specific nonsynonymous polymorphism in Nsdhl, which codes for sterol-4-alpha-carboxylate 3-dehydrogenase in the cholesterol synthesis pathway. Although many lipid quantitative trait locus have been reported previously, these data suggest there are additional genes left to be identified that control lipid levels and that can provide new pharmaceutical targets.

Randomized trial of the effects of cholesterol-lowering dietary treatment on psychological function.

PubMed

Wardle, J; Rogers, P; Judd, P; Taylor, M A; Rapoport, L; Green, M; Nicholson Perry, K

2000-05-01

Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning. This study was designed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [198 mg/dL]) to either a low-fat diet, a Mediterranean diet, or a waiting-list control. Cholesterol levels, psychological well-being (depression, anxiety, hostility), and cognitive function were assessed at baseline, 6 weeks, and 12 weeks. Total serum cholesterol levels fell significantly more in the intervention groups (8.2% reduction) than in the control group (P <0.001). All three groups showed a modest improvement in psychological well-being during the 12-week treatment period, but there were no differences among the groups. There were no between-group differences on three measures of cognitive function, but for a fourth measure, which involved the task with the greatest processing load, the two intervention groups did significantly worse (P <0.001) than the control group. The change in performance was correlated with the change in total serum cholesterol level (r = 0. 21, P = 0.01). Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood. There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests, but additional studies will be required to determine the relevance of this finding.

Strategies for increasing house staff management of cholesterol with inpatients.

PubMed

Boekeloo, B O; Becker, D M; Levine, D M; Belitsos, P C; Pearson, T A

1990-01-01

This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

[Serum lipids and blood pressure levels in the +Mapuche population living in the Chilean region of Araucanía].

PubMed

Stockins, B; Larenas, G; Charles, M; Standen, D; Espinoza, O; Illesca, M; Opazo, J A; Carrasco, B; Lanas, F; Davis, M

1998-11-01

Chilean aboriginal populations (Mapuche) predominantly live in the region of Araucanía, in the southern part of the country. Their cardiovascular risk factors have not been systematically assessed. To study the prevalence of cardiovascular risk factors in the Mapuche population. Blood pressure, weight, height, dietary habits, fasting serum total cholesterol, HDL cholesterol and triglycerides were measured in 1.948 adults living in 28 Mapuche communities. Thirteen percent of males and 16% of females had high blood pressure. Body mass index was 25.5 kg/m2 in males and 28.1 kg/m2 in females. Forty five percent of women and 24% of men were classified as obese. Mean serum total cholesterol was 186.7 +/- 9.6 mg/dl, HDL cholesterol was 58.7 +/- 30.7 mg/dl, total cholesterol/HDL cholesterol was 3.4 +/- 2 and triglycerides were 155.2 +/- 91.2 mg/dl. Twenty eight percent of males and 9.6% of females smoked. Mapuche individuals have higher levels of HDL cholesterol a better total cholesterol/HDL cholesterol ratio and lower frequency of smoking than non aboriginal Chileans subjects.

Cholesterol Regulates μ-Opioid Receptor-Induced β-Arrestin 2 Translocation to Membrane Lipid RaftsS⃞

PubMed Central

Qiu, Yu; Wang, Yan; Chen, Hong-Zhuan; Loh, Horace H.

2011-01-01

μ-Opioid receptor (OPRM1) is mainly localized in lipid raft microdomains but internalizes through clathrin-dependent pathways. Our previous studies demonstrated that disruption of lipid rafts by cholesterol-depletion reagent blocked the agonist-induced internalization of OPRM1 and G protein-dependent signaling. The present study demonstrated that reduction of cholesterol level decreased and culturing cells in excess cholesterol increased the agonist-induced internalization and desensitization of OPRM1, respectively. Further analyses indicated that modulation of cellular cholesterol level did not affect agonist-induced receptor phosphorylation but did affect membrane translocation of β-arrestins. The translocation of β-arrestins was blocked by cholesterol reduction, and the effect could be reversed by incubating with cholesterol. OptiPrep gradient separation of lipid rafts revealed that excess cholesterol retained more receptors in lipid raft domains and facilitated the recruitment of β-arrestins to these microdomains upon agonist activation. Moreover, excess cholesterol could evoke receptor internalization and protein kinase C-independent extracellular signal-regulated kinases activation upon morphine treatment. Therefore, these results suggest that cholesterol not only can influence OPRM1 localization in lipid rafts but also can effectively enhance the recruitment of β-arrestins and thereby affect the agonist-induced trafficking and agonist-dependent signaling of OPRM1. PMID:21518774

Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

PubMed Central

Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

2017-01-01

Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

[ECS guidelines 2016 - dyslipidaemias].

PubMed

Sinning, D; Landmesser, U

2016-12-01

Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies). In patients with a very high risk for cardiovascular events it is recommended to treat to an LDL cholesterol target of less than 70 mg/dl. Moreover, the new guidelines now additionally recommend a > 50% reduction of LDL cholesterol in patients with very high cardiovascular risk patients and baseline levels between 70 and 135 mg/dl as well as in patients with high cardiovascular risk and baseline LDL cholesterol levels between 100 and 200 mg/dl. Statins are recommended as first-line medicinal treatment and the LDL cholesterol goals given imply the more frequent use of maximum tolerated statin therapy, in particular for patients with very high cardiovascular risk. Treatment with ezetimibe in patients with substantially elevated LDL cholesterol levels despite maximum tolerated statin therapy has now received a stronger recommendation (currently IIa recommendation). The guidelines also now include the potential use of the novel proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and a recent ESC/EAS consensus document provides more detailed information on which patients can be considered for treatment with PCSK9 inhibitors, i. e. in particular patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL cholesterol levels despite maximum tolerated statin and ezetimibe therapy.

Statins attenuate but do not eliminate the reverse epidemiology of total serum cholesterol in patients with non-ischemic chronic heart failure.

PubMed

Fröhlich, Hanna; Raman, Nandita; Täger, Tobias; Schellberg, Dieter; Goode, Kevin M; Kazmi, Syed; Grundtvig, Morten; Hole, Torstein; Cleland, John G F; Katus, Hugo A; Agewall, Stefan; Clark, Andrew L; Atar, Dan; Frankenstein, Lutz

2017-07-01

In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).

PubMed

Ballantyne, Christie M; Bays, Harold E; Kastelein, John J; Stein, Evan; Isaacsohn, Jonathan L; Braeckman, Rene A; Soni, Paresh N

2012-10-01

AMR101 is an ω-3 fatty acid agent containing ≥96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid. The efficacy and safety of AMR101 were evaluated in this phase 3, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial (ANCHOR) in high-risk statin-treated patients with residually high triglyceride (TG) levels (≥200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (≥40 and <100 mg/dl). Patients (n = 702) on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p <0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p <0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-low-density lipoprotein cholesterol (24.4%), lipoprotein-associated phospholipase A(2) (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p <0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo. In conclusion, AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, lipoprotein-associated phospholipase A(2), and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations. Copyright © 2012 Elsevier Inc. All rights reserved.

High Blood Cholesterol

MedlinePlus

... high blood cholesterol: Chronic kidney disease Diabetes HIV Hypothyroidism Overweight and obesity Polycystic ovary syndrome Inflammatory diseases ... your thyroid hormone levels can help rule out hypothyroidism as a cause of high blood levels of ...

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial.

PubMed

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva ® ) and the reference formulation (Lipitor ® ) of atorvastatin, both at a dosage of 20 mg once daily. This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (-43.9%±15.3% in the generic group, -43.3%±17.0% in the reference group, P =0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P =0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P =0.804). The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia.

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial

PubMed Central

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

Purpose This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva®) and the reference formulation (Lipitor®) of atorvastatin, both at a dosage of 20 mg once daily. Methods This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Results Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (−43.9%±15.3% in the generic group, −43.3%±17.0% in the reference group, P=0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P=0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P=0.804). Conclusion The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia. PMID:28814835

High-alkali low-temperature polysulfide pulping (HALT) of Scots pine.

PubMed

Paananen, Markus; Sixta, Herbert

2015-10-01

High-alkali low-temperature polysulfide pulping (HALT) was effectively utilised to prevent major polysaccharide losses while maintaining the delignification rate. A yield increase of 6.7 wt% on wood was observed for a HALT pulp compared to a conventionally produced kappa number 60 pulp with comparable viscosity. Approximately 70% of the yield increase was attributed to improved galactoglucomannan preservation and 30% to cellulose. A two-stage oxygen delignification sequence with inter-stage peroxymonosulphuric acid treatment was used to ensure delignification to a bleachable grade. In a comparison to conventional pulp, HALT pulp effectively maintained its yield advantage. Diafiltration trials indicate that purified black liquor can be directly recycled, as large lignin fractions and basically all dissolved polysaccharides were separated from the alkali-rich BL. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S

PubMed Central

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.

2015-01-01

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 < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles. PMID:25964513

Depletion of cellular cholesterol interferes with intracellular trafficking of liposome-encapsulated ovalbumin.

PubMed

Rao, Mangala; Peachman, Kristina K; Alving, Carl R; Rothwell, Stephen W

2003-12-01

Cholesterol is a major constituent of plasma cell membranes and influences the functions of proteins residing in the membrane. To assess the role of cholesterol in phagocytosis and intracellular trafficking of liposomal antigen, macrophages were treated with inhibitors of cholesterol biosynthesis for various time periods and levels of cholesterol depletion were assessed by thin layer chromatography. In control macrophages, cholesterol was present in the plasma membrane and in intracellular stores, as visualised by staining with the cholesterol-binding compound filipin, whereas macrophages treated with cholesterol inhibitors failed to stain with filipin. However, these macrophages were still capable of phagocytosis as evidenced by their internalisation of fluorescent-labelled bacteria and liposome-encapsulated Texas red labelled-ovalbumin, L(TR-OVA). While fluorescent ovalbumin (OVA) was consistently transported to the Golgi in macrophages incubated with L(TR-OVA), in cells treated with cholesterol inhibitors, OVA remained spread diffusely throughout the cytoplasm. Even though the mean fluorescence intensity of MHC class I molecules on cholesterol inhibitor-treated macrophages was equivalent to that of the control macrophages, the amount of MHC class I-liposomal OVA-peptide complex detected on the cell surface of cholesterol inhibitor-treated macrophages, was only 45.6 +/- 7.4% (n = 4, mean +/- SEM) of control levels after intracellular processing of L(OVA). We conclude that cholesterol depletion does not eliminate phagocytosis or MHC class I surface expression, but does affect the trafficking and consequently the MHC class I antigen-processing pathway.

[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].

PubMed

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.

High cholesterol level is essential for myelin membrane growth.

PubMed

Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

2005-04-01

Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

An Ounce of Prevention

ERIC Educational Resources Information Center

Sternbach, David

2004-01-01

The quality of students' lives can be greatly enhanced through music, and teachers know that musicians at all levels risk injury when they practice and perform. Overuse injuries are painful, disrupt progress, and can even permanently halt performing careers. Expert treatment can be difficult to find on short notice, especially when an injured…

Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

PubMed

Zhang, Jifeng; Niimi, Manabu; Yang, Dongshan; Liang, Jingyan; Xu, Jie; Kimura, Tokuhide; Mathew, Anna V; Guo, Yanhong; Fan, Yanbo; Zhu, Tianqing; Song, Jun; Ackermann, Rose; Koike, Yui; Schwendeman, Anna; Lai, Liangxue; Pennathur, Subramaniam; Garcia-Barrio, Minerva; Fan, Jianglin; Chen, Y Eugene

2017-06-01

CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B-containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α-induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet-induced atherosclerosis in rabbits. © 2017 American Heart Association, Inc.

Effects of Chinese Dietary Pattern of Fat Content, n-6/n-3 Polyunsaturated Fatty Acid Ratio, and Cholesterol Content on Lipid Profile in Rats

PubMed Central

Zou, Xian-Guo; Huang, Yu-Hua; Xu, Tong-Cheng; Fan, Ya-Wei; Li, Jing

2018-01-01

This study aims to investigate the effect of Chinese diet pattern of fat content (30% or 36.06%), n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (5 : 1 or 9 : 1), and cholesterol content (0.04 or 0.057 g/kg total diet) on lipid profile using a rat model. Results showed that rats' body weights (BWs) were controlled by the simultaneous intakes of cholesterol level of 0.04 g/kg total diet and n-6/n-3 ratio of 5 : 1. In addition, under high-fat diet, increased cholesterol feeding led to increased total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels and decreased triacylglycerols (TG) in rats' plasma. However, high density lipoprotein cholesterol (HDL-C) level and the ratios of HDL-C/LDL-C and HDL-C/TC in rats' plasma increased in response to simultaneous intakes of low n-6/n-3 ratio (5 : 1) and cholesterol (0.04 g/kg total diet) even under high-fat diet. Moreover, as the n-6/n-3 PUFA ratio in the diet decreased, the proportion of n-3 PUFAs increased in plasma, liver, and muscle and resulted in the decrease of n-6/n-3 PUFA ratio. PMID:29744358

Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-rheumatoid arthritis patients.

PubMed

Liao, Katherine P; Liu, Jun; Lu, Bing; Solomon, Daniel H; Kim, Seoyoung C

2015-05-01

Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls. Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors. In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (≤91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [≤43.0 mg/dl] versus highest quintile [>71.0 mg/dl]). The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort. © 2015, American College of Rheumatology.

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

PubMed

Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying

2014-01-01

To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (P<0.05). A higher level of total cholesterol was associated with the E4 allele (adjusted odds ratio 1.689, 95% confidence interval 1.223-2.334, P<0.01). However, no association was found between APOE status and serum levels of glucose (adjusted odds ratio 0.981, 95% confidence interval 0.720-1.336, P=0.903) or total triglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759-1.429, P=0.800). A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides.

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels

PubMed Central

Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Sato, Akira; Miyake, Shogo; Morino, Yoshihiro; Yamauchi, Takao; Muramatsu, Toshiya; Hibi, Kiyoshi; Terashima, Mitsuyasu; Suzuki, Hiroshi; Michishita, Ichiro

2016-01-01

Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004]. Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline. University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311). PMID:27040362

Cholesterol, Triglycerides, and the Five-Factor Model of Personality

PubMed Central

Sutin, Angelina R.; Terracciano, Antonio; Deiana, Barbara; Uda, Manuela; Schlessinger, David; Lakatta, Edward G.; Costa, Paul T.

2010-01-01

Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.56–4.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality. PMID:20109519

High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

PubMed Central

Ossoli, Alice; Pavanello, Chiara

2016-01-01

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

Lipid profile in oral submucous fibrosis.

PubMed

Mehrotra, Ravi; Pandya, Shruti; Chaudhary, Ajay Kumar; Singh, Himanshu Pratap; Jaiswal, Ritesh Kumar; Singh, Mangal; Gupta, S C; Singh, Mamta

2009-07-24

Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption. In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed. A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF. The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.

Enzymatic measurement of free and esterified cholesterol levels in plasma and other biological preparations using the oxygen electrode in a modified glucose analyzer.

PubMed

Dietschy, J M; Weeks, L E; Delente, J J

1976-12-01

A method is described for assaying free and esterified cholesterol using the oxygen electrode in a modified glucose analyzer to measure the relative amount of oxygen utilization taking place during oxydation of free cholesterol by the enzyme, cholesterol oxidase. A second enzyme, cholesterol ester hydrolase, is utilized to generate free cholesterol from cholesterol esters. This assay procedure is rapid, specific, reproducible and applicable to the measurement of free and esterified cholesterol carried in the major plasma lipoprotein fractions of man and the rat and, in addition, it can be utilized for the assay of sterols in subcellular fractions of cells.

Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol levels and reduce liver cholesterol and triacylglycerol contents similar to PPARalpha activations in C57BL/6 mice.

PubMed

Miura, Yutaka; Hosono, Mayu; Oyamada, Chiaki; Odai, Hideharu; Oikawa, Shinichi; Kondo, Keiji

2005-04-01

The effects of dietary isohumulones, the main components accounting for the bitter taste of beer, on lipid metabolism were examined. Young female C57BL/6N mice were fed diets containing isomerized hop extract (IHE), which consists mainly of isohumulones. Administration of IHE with an atherogenic (high-fat and high-cholesterol) diet for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P<0.01), along with a concomitant reduction in the atherosclerosis index, an increase in liver weight and a decrease in body weight gain in a dose-dependent manner. When animals received IHE with either a cholesterol or a basal diet for 1 week, significant decreases in the liver content of cholesterol (P<0.01) and triacylglycerol (cholesterol diet, P<0.01) were observed. Quantitative analyses of hepatic mRNA levels revealed that IHE administration resulted in up-regulation of mRNA for acyl-CoA oxidase, acyl-CoA synthetase, hydroxymethylglutaryl-CoA synthetase, lipoprotein lipase and fatty acid transport protein, and down-regulation of mRNA for Apo CIII and Apo AI. Administration of purified isohumulones effectively resulted in the same changes as IHE. Administration of fenofibrate, an agonist for PPARalpha, with a cholesterol diet caused marked hepatomegaly, an increase in plasma HDL-cholesterol, a decrease in hepatic cholesterol content, and alterations in hepatic mRNA levels similar to those observed in mice given IHE. Taken together, these results suggest that the modulation of lipid metabolism observed in mice fed diets containing isohumulones is, at least in part, mediated by activation of PPARalpha.

Beta-glucan- or rice bran-enriched foods: a comparative crossover clinical trial on lipidic pattern in mildly hypercholesterolemic men.

PubMed

Rondanelli, M; Opizzi, A; Monteferrario, F; Klersy, C; Cazzola, R; Cestaro, B

2011-07-01

There has been growing interest in using dietary intervention to improve the lipid profile. This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men. The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods. After this adaptation period, volunteers were randomly assigned to follow a crossover, controlled trial that consisted of two treatment with beta-glucan- or rice bran-enriched foods, each of 4 weeks, with a 3-week wash-out, like the adaptation period, between periods. Fasted blood samples were collected on days 0, 21, 49, 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol (primary outcome), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B and glucose levels. Twenty-four men (mean age: 50.3±5.3, mean body mass index: 24.9±1.9) completed the 14-week trial. Subjects in the 3-week adaptation period experienced significant reductions in the mean level of LDL cholesterol, total cholesterol, total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, apo A-I, apo A-I/apo B and glucose. During the intervention diet periods, a difference was found between treatment groups for the mean change in LDL (0.21 (95% confidence interval (CI): 0.02-0.40), P=0.033) and total cholesterol (0.34 (95% CI: 0.20-0.47), P<0.001). Other parameters evaluated were not significantly affected by the diet consumed. The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels, compared with rice bran-enriched foods.

Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation

PubMed Central

Vest, Amanda R.; Kennel, Peter J.; Maldonado, Dawn; Young, James B.; Mountis, Maria M.; Naka, Yoshifumi; Colombo, Paolo C.; Mancini, Donna M.; Starling, Randall C.; Schulze, P. Christian

2017-01-01

Background Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure. Methods and Results A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125–150 mg/dL, 67–85 mg/dL, 32–42 mg/dL, and 97–126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212–0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092–0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support. Conclusions Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support. PMID:27623768

Effect of exercise training on plasma levels and functional properties of high-density lipoprotein cholesterol in the metabolic syndrome.

PubMed

Casella-Filho, Antonio; Chagas, Antonio Carlos P; Maranhão, Raul C; Trombetta, Ivani C; Cesena, Fernando H Y; Silva, Vanessa M; Tanus-Santos, Jose Eduardo; Negrão, Carlos E; da Luz, Protasio L

2011-04-15

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions' antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Relationship between Serum Ferritin Levels and Dyslipidemia in Korean Adolescents

PubMed Central

Kim, Young-Eun; Roh, Yong-Kyun; Ju, Sang-Yhun; Yoon, Yeo-Joon; Nam, Ga-Eun; Nam, Hyo-Yun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo

2016-01-01

Background Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. Methods We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. Results In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. Conclusion Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor. PMID:27070153

5 Tips: What You Should Know About High Blood Cholesterol

MedlinePlus

... marketed for improving cholesterol. The dietary supplements red yeast rice, flaxseed, and garlic, are among the many ... supplements are effective in reducing cholesterol levels. Red yeast rice. Some red yeast rice products contain substances ...

9 CFR 317.362 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2013 CFR

2013-01-01

... acids, and cholesterol content. 317.362 Section 317.362 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.362 Nutrient content claims for fat, fatty acids, and cholesterol content. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a product may only be...

9 CFR 381.462 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2013 CFR

2013-01-01

... acids, and cholesterol content. 381.462 Section 381.462 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.462 Nutrient content claims for fat, fatty acids, and cholesterol content. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a product may only be...

9 CFR 381.462 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2014 CFR

2014-01-01

... acids, and cholesterol content. 381.462 Section 381.462 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.462 Nutrient content claims for fat, fatty acids, and cholesterol content. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a product may only be...

9 CFR 317.362 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2014 CFR

2014-01-01

... acids, and cholesterol content. 317.362 Section 317.362 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.362 Nutrient content claims for fat, fatty acids, and cholesterol content. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a product may only be...

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

PubMed

Wang, I-Kuan; Liu, Chung-Hsiang; Yen, Tzung-Hai; Jeng, Jiann-Shing; Hsu, Shih-Pin; Chen, Chih-Hung; Lien, Li-Ming; Lin, Ruey-Tay; Chen, An-Chih; Lin, Huey-Juan; Chi, Hsin-Yi; Lai, Ta-Chang; Sun, Yu; Lee, Siu-Pak; Sung, Sheng-Feng; Chen, Po-Lin; Lee, Jiunn-Tay; Chiang, Tsuey-Ru; Lin, Shinn-Kuang; Muo, Chih-Hsin; Ma, Henry; Wen, Chi-Pang; Sung, Fung-Chang; Hsu, Chung Y

2017-06-01

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-01-01

Epidemiological studies show that people with low level of total cholesterol have a greater risk of death due to cancer, predominantly lung cancer. The aim of our study was to evaluate serum level of LDL cholesterol and lipoprotein electrophoresis pattern in patients with small cell lung cancer and their dependence on clinical stage of the neoplasm. The studied group consisted of 34 patients with newly diagnosed small cell lung cancer and 39 healthy controls. Fasting level of LDL cholesterol was analyzed and lipoprotein electrophoresis was performed. There were no statistically significant differences of evaluated serum lipid parameters between lung cancer patients and controls, and between the clinical stages of small cell lung cancer.

In Situ Probing of Cholesterol in Astrocytes at the Single Cell Level using Laser Desorption Ionization Mass Spectrometric Imaging with Colloidal Silver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perdian, D.C.; Cha, Sangwon; Oh, Jisun

2010-03-18

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

Ionizing radiation from Chernobyl affects development of wild carrot plants.

PubMed

Boratyński, Zbyszek; Arias, Javi Miranda; Garcia, Cristina; Mappes, Tapio; Mousseau, Timothy A; Møller, Anders P; Pajares, Antonio Jesús Muñoz; Piwczyński, Marcin; Tukalenko, Eugene

2016-12-16

Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.

Ionizing radiation from Chernobyl affects development of wild carrot plants

NASA Astrophysics Data System (ADS)

Boratyński, Zbyszek; Arias, Javi Miranda; Garcia, Cristina; Mappes, Tapio; Mousseau, Timothy A.; Møller, Anders P.; Pajares, Antonio Jesús Muñoz; Piwczyński, Marcin; Tukalenko, Eugene

2016-12-01

Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.

Regulation of neuronal APL-1 expression by cholesterol starvation.

PubMed

Wiese, Mary; Antebi, Adam; Zheng, Hui

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP). While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD), sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE) gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1), and lrp-1 (lipoprotein receptor-related protein 1), suggesting a potential interaction between apl-1 and cholesterol metabolism. Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

Higher HDL cholesterol is associated with better cognitive function: the Maine-Syracuse study.

PubMed

Crichton, Georgina E; Elias, Merrill F; Davey, Adam; Sullivan, Kevin J; Robbins, Michael A

2014-11-01

Few studies have examined associations between different subcategories of cholesterol and cognitive function. We examined relationships between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular risk factors. Cross-sectional analyses were undertaken on data from 540 participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and triglyceride levels were obtained. Cognitive function was assessed using a thorough neuropsychological test battery, including domains of cognitive function indexed by multiple cognitive tests. The cognitive outcomes studied were as follows: Visual-Spatial Memory and Organization, Verbal and Working Memory, Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini-Mental State Examination (MMSE). Significant positive associations were observed between HDL-cholesterol and the Global Composite score, Working Memory, and the MMSE after adjustment for demographic and cardiovascular risk factors. Participants with desirable levels of HDL (≥60 mg/dL) had the highest scores on all cognitive outcomes. There were no significant associations observed between TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL-cholesterol was related to a composite of Working Memory tests and for general measures of cognitive ability when adjusted for cardiovascular variables. We speculate that persons over 60 are survivors and thus less likely to show cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides. Longitudinal studies are needed to examine relations between specific cognitive abilities and the different subcategories of cholesterol.

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

PubMed Central

St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

2002-01-01

Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

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

NASA Astrophysics Data System (ADS)

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.

Association of CETP Gene Variants With Risk for Vascular and Nonvascular Diseases Among Chinese Adults

PubMed Central

Bennett, Derrick A.; Holmes, Michael V.; Boxall, Ruth; Guo, Yu; Bian, Zheng; Yang, Ling; Sansome, Sam; Chen, Yiping; Du, Huaidong; Yu, Canqing; Hacker, Alex; Reilly, Dermot F.; Tan, Yunlong; Hill, Michael R.; Chen, Junshi; Peto, Richard; Shen, Hongbing; Collins, Rory; Clarke, Robert; Li, Liming; Walters, Robin G.; Chen, Zhengming

2017-01-01

Importance Increasing levels of high-density lipoprotein (HDL) cholesterol through pharmacologic inhibition of cholesteryl ester transfer protein (CETP) is a potentially important strategy for prevention and treatment of cardiovascular disease (CVD). Objective To use genetic variants in the CETP gene to assess potential risks and benefits of lifelong lower CETP activity on CVD and other outcomes. Design, Setting, and Participants This prospective biobank study included 151 217 individuals aged 30 to 79 years who were enrolled from 5 urban and 5 rural areas of China from June 25, 2004, through July 15, 2008. All participants had baseline genotype data, 17 854 of whom had lipid measurements and 4657 of whom had lipoprotein particle measurements. Median follow-up of 9.2 years (interquartile range, 8.2-10.1 years) was completed January 1, 2016, through linkage to health insurance records and death and disease registries. Exposures Five CETP variants, including an East Asian loss-of-function variant (rs2303790), combined in a genetic score weighted to associations with HDL cholesterol levels. Main Outcomes and Measures Baseline levels of lipids and lipoprotein particles, cardiovascular risk factors, incidence of carotid plaque and predefined major vascular and nonvascular diseases, and a phenome-wide range of diseases. Results Among the 151 217 individuals included in this study (58.4% women and 41.6% men), the mean (SD) age was 52.3 (10.9) years. Overall, the mean (SD) low-density lipoprotein (LDL) cholesterol level was 91 (27) mg/dL; HDL cholesterol level, 48 (12) mg/dL. CETP variants were strongly associated with higher concentrations of HDL cholesterol (eg, 6.1 [SE, 0.4] mg/dL per rs2303790-G allele; P = 9.4 × 10−47) but were not associated with lower LDL cholesterol levels. Within HDL particles, cholesterol esters were increased and triglycerides reduced, whereas within very low-density lipoprotein particles, cholesterol esters were reduced and triglycerides increased. When scaled to 10-mg/dL higher levels of HDL cholesterol, the CETP genetic score was not associated with occlusive CVD (18 550 events; odds ratio [OR], 0.98; 95% CI, 0.91-1.06), major coronary events (5767 events; OR, 1.08; 95% CI, 0.95-1.22), myocardial infarction (3118 events; OR, 1.14; 95% CI, 0.97-1.35), ischemic stroke (13 759 events; OR, 0.94; 95% CI, 0.86-1.02), intracerebral hemorrhage (6532 events; OR, 0.94; 95% CI, 0.83-1.06), or other vascular diseases or carotid plaque. Similarly, rs2303790 was not associated with any vascular diseases or plaque. No associations with nonvascular diseases were found other than an increased risk for eye diseases with rs2303790 (4090 events; OR, 1.43; 95% CI, 1.13-1.80; P = .003). Conclusions and Relevance CETP variants were associated with altered HDL metabolism but did not lower LDL cholesterol levels and had no significant association with risk for CVD. These results suggest that in the absence of reduced LDL cholesterol levels, increasing HDL cholesterol levels by inhibition of CETP may not confer significant benefits for CVD. PMID:29141072

Plant sterols in food: No consensus in guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weingärtner, Oliver, E-mail: oweingartner@aol.com; Baber, Ronny; LIFE – Leipziger Forschungszentrum für Zivilisationserkrankungen, Universität Leipzig, Leipzig

2014-04-11

Highlights: • Plant sterols are used as food supplement to reduce serum cholesterol levels. • Reductions in serum cholesterol levels are achieved at the expense of increased plant sterol levels. • The potential atherogenicity of increased serum plant sterol levels is controversially debated. • This dispute is reflected by different guideline recommendations in regard to plant sterols. - Abstract: Plant sterols are supplemented in foods to reduce cardiovascular risk. Randomized controlled trials show 2 g of plant sterols a day reduce serum cholesterol by about 10%. This reduction in serum cholesterol levels is achieved at the expense of increased serummore » plant sterol levels. Findings in patients with phytosterolemia, in experimental studies and in clinical trials have lead to speculations that plant sterols might be atherogenic. In view of emerging safety issues the role of plant sterols in cardiovascular prevention has become controversial. This review reflects the ongoing controversial scientific debate and points out recent developments in guidelines of national and international societies.« less

Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol

PubMed Central

Dastani, Zari; Ruel, Isabelle L; Engert, James C; Genest, Jacques; Marcil, Michel

2007-01-01

Background Niemann-Pick disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol. Methods Two common coding polymorphisms in the SMPD1 gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5th percentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25th percentile. Results For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different. Conclusion These results suggest that the two common coding variants at the SMPD1 gene locus are not associated with low HDL-cholesterol levels in the French Canadian population. PMID:18088425

Inhibition of cholesterol absorption and synthesis in rats by sesamin.

PubMed

Hirose, N; Inoue, T; Nishihara, K; Sugano, M; Akimoto, K; Shimizu, S; Yamada, H

1991-04-01

The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin.

Novel gene-by-environment interactions: APOB and NPC1L1 variants affect the relationship between dietary and total plasma cholesterol[S

PubMed Central

Kim, Daniel S.; Burt, Amber A.; Ranchalis, Jane E.; Jarvik, Ella R.; Rosenthal, Elisabeth A.; Hatsukami, Thomas S.; Furlong, Clement E.; Jarvik, Gail P.

2013-01-01

Cardiovascular disease (CVD) is the leading cause of death in developed countries. Plasma cholesterol level is a key risk factor in CVD pathogenesis. Genetic and dietary variation both influence plasma cholesterol; however, little is known about dietary interactions with genetic variants influencing the absorption and transport of dietary cholesterol. We sought to determine whether gut expressed variants predicting plasma cholesterol differentially affected the relationship between dietary and plasma cholesterol levels in 1,128 subjects (772/356 in the discovery/replication cohorts, respectively). Four single nucleotide polymorphisms (SNPs) within three genes (APOB, CETP, and NPC1L1) were significantly associated with plasma cholesterol in the discovery cohort. These were subsequently evaluated for gene-by-environment (GxE) interactions with dietary cholesterol for the prediction of plasma cholesterol, with significant findings tested for replication. Novel GxE interactions were identified and replicated for two variants: rs1042034, an APOB Ser4338Asn missense SNP and rs2072183 (in males only), a synonymous NPC1L1 SNP in linkage disequilibrium with SNPs 5′ of NPC1L1. This study identifies the presence of novel GxE and gender interactions implying that differential gut absorption is the basis for the variant associations with plasma cholesterol. These GxE interactions may account for part of the “missing heritability” not accounted for by genetic associations. PMID:23482652

Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in Taiwan - a cohort study.

PubMed

Lee, Ya-Ling; Li, Wan-Chun; Tsai, Tung-Hu; Chiang, Hsin-Yu; Ting, Chin-Tsung

2016-04-19

Curative surgical resection (CSR) remains the most effective therapeutic intervention for patients with hepatocellular carcinoma (HCC); however, frequent post-surgical recurrence leads to high cancer related mortality. This study aimed to clarify the role of body mass index (BMI) and serum cholesterol level in predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC patients including 213 BMIhigh and 271 BMIlow patients were included. Overall survival (OS) and recurrence-free survival (RFS) rates were examined in patients with differential BMI and serum cholesterol level. The analysis showed that significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in groups with differential serum cholesterol levels among BMIlow and BMIhigh patients indicated that the BMIlow/Chollow patients exhibited the significant lower cumulative OS and RFS rates in comparison with the remaining subjects (P-value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the coexistence of low BMI and low serum cholesterol level could serve as prognostic factors to predict post-operative outcomes in HCC patients undergoing surgical hepatectomy.

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

PubMed

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

2005-04-30

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

Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

PubMed

Manti, S; Leonardi, S; Panasiti, I; Arrigo, T; Salpietro, C; Cuppari, C

2017-11-01

Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (p<0.05), LDL (p<0.05), and tryglicerides (p<0.001), but negatively with HDL (p<0.05). Serum levels of IL-10 were lower in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). Serum IL-10 levels significantly related also with serum cholesterol levels: negatively with total cholesterol (p<0.001), LDL (p<0.05), and triglycerides (p<0.05), but positively with HDL (p<0.05). Serum IL-17 and IL-23 levels showed the same trend. They were significantly higher in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). In particular, serum IL-17 and IL-23 values positively correlated with serum total IgE levels (p<0.05); serum total cholesterol levels (p<0.001); serum LDL levels (p<0.001); serum triglycerides levels (p<0.05). Although not statistically significant, an inverse correlation has been noted between serum IL-17, IL-23 and HDL levels. These findings support the notion that dyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study

PubMed Central

2013-01-01

Background The microsomal triglyceride transfer protein (MTTP) is encoded by the MTTP gene that is regulated by cholesterol in humans. Previous studies investigating the effect of MTTP on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in MTTP alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels. Methods The -164T > C polymorphism was genotyped in a case-cohort study (193 incident myocardial infarction (MI) and 131 incident ischemic stroke (IS) cases and 1 978 non-cases) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study, comprising 27 548 middle-aged subjects. The Heinz Nixdorf Recall study (30 CVD cases and 1 188 controls) was used to replicate our findings. Results Genotype frequencies were not different between CVD and CVD free subjects (P = 0.79). We observed an interaction between the -164T > C polymorphism and total cholesterol levels in relation to future CVD. Corresponding stratified analyses showed a significant increased risk of CVD (HRadditve = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HRadditive was 1.06, 95% CI: 0.33 to 3.40 for individuals in the Heinz Nixdorf Recall study. A borderline significant decrease in CVD risk was observed in subjects with cholesterol levels ≥200 mg/dL (HRadditve = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HRadditve = 0.60, 95% CI: 0.29 to 1.25). Conclusions Our study suggests an interaction between MTTP -164T > C functional polymorphism with total cholesterol levels. Thereby risk allele carriers with low cholesterol levels may be predisposed to an increased risk of developing CVD, which seems to be abolished among risk allele carriers with high cholesterol levels. PMID:23356586

A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis.

PubMed

Chua, Ngee Kiat; Howe, Vicky; Jatana, Nidhi; Thukral, Lipi; Brown, Andrew J

2017-12-08

Cholesterol biosynthesis in the endoplasmic reticulum (ER) is tightly controlled by multiple mechanisms to regulate cellular cholesterol levels. Squalene monooxygenase (SM) is the second rate-limiting enzyme in cholesterol biosynthesis and is regulated both transcriptionally and post-translationally. SM undergoes cholesterol-dependent proteasomal degradation when cholesterol is in excess. The first 100 amino acids of SM (designated SM N100) are necessary for this degradative process and represent the shortest cholesterol-regulated degron identified to date. However, the fundamental intrinsic characteristics of this degron remain unknown. In this study, we performed a series of deletions, point mutations, and domain swaps to identify a 12-residue region (residues Gln-62-Leu-73), required for SM cholesterol-mediated turnover. Molecular dynamics and circular dichroism revealed an amphipathic helix within this 12-residue region. Moreover, 70% of the variation in cholesterol regulation was dependent on the hydrophobicity of this region. Of note, the earliest known Doa10 yeast degron, Deg1, also contains an amphipathic helix and exhibits 42% amino acid similarity with SM N100. Mutating SM residues Phe-35/Ser-37/Leu-65/Ile-69 into alanine, based on the key residues in Deg1, blunted SM cholesterol-mediated turnover. Taken together, our results support a model whereby the amphipathic helix in SM N100 attaches reversibly to the ER membrane depending on cholesterol levels; with excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal. Our findings shed new light on the regulation of a key cholesterol synthesis enzyme, highlighting the conservation of critical degron features from yeast to humans. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial.

PubMed

Bundy, Rafe; Walker, Ann F; Middleton, Richard W; Wallis, Carol; Simpson, Hugh C R

2008-09-01

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.

Higher high-density lipoprotein cholesterol in African-American women with polycystic ovary syndrome compared with Caucasian counterparts.

PubMed

Koval, Kathryn W; Setji, Tracy L; Reyes, Eric; Brown, Ann J

2010-09-01

Studies have demonstrated lipid differences among African-Americans and Caucasians and between women with polycystic ovary syndrome (PCOS) and normally ovulating women. However, few studies have examined racial differences in lipoprotein levels in women with PCOS. This study compared lipoprotein levels in African-American and Caucasian women with PCOS. We performed a retrospective chart review of 398 subjects seen as new patients for PCOS at the Duke University Medical Center Endocrinology Clinic in Durham, NC. We identified 126 charts appropriate for review, based on a diagnosis of PCOS (using the 1990 National Institutes of Health criteria), a self-reported race of either Caucasian or African-American, and a body mass index (BMI) higher than 25. We excluded patients taking glucophage, oral contraceptives, or lipid-lowering medications. Age, BMI, total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, random triglycerides (TG), and oral glucose tolerance test measurements were collected and included in the analysis. African-American women with PCOS had higher HDL cholesterol levels (52.6 vs. 47.5 mg/dl, P = 0.019), lower non-HDL cholesterol (134.1 vs. 154.6 mg/dl, P = 0.046), and lower TG levels (97.5 vs. 168.2 mg/dl, P < 0.001) than Caucasian women. These differences could not be attributed to age, BMI, or differences in insulin resistance as determined by homeostasis model assessment of insulin resistance. African-American women with PCOS appear to have a more favorable lipid profile than Caucasian women with PCOS having higher HDL cholesterol, lower non-HDL cholesterol, and lower TG when BMI and insulin resistance are equal.

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study)

PubMed Central

Aguilar-Salinas, Carlos A; Assis-Luores-Vale, Andréia; Stockins, Benjamín; Rengifo, Hector Mario; Filho, José Dondici; Neto, Abrahão Afiune; Rabelo, Lísia Marcílio; Torres, Kerginaldo Paulo; Oliveira, José Egídio Paulo de; Machado, Carlos Alberto; Reyes, Eliana; Saavedra, Victor; Florenzano, Fernando; Hernández, Ma Victoria; Jiménez, Sergio Hernandez; Ramírez, Erika; Vazquez, Cuauhtémoc; Salinas, Saul; Hernández, Ismael; Medel, Octavio; Moreno, Ricardo; Lugo, Paula; Alvarado, Ricardo; Mehta, Roopa; Gutierrez, Victor; Gómez Pérez, Francisco J

2004-01-01

Background Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. Methods Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6–3.9 mM/l and HDL cholesterol ≤ 1.05 mM/l for women and ≤ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. Results After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m2) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. Conclusions Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated. PMID:15272932

APOC3 Loss-of-Function Mutations, Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Cardiovascular Risk: Mediation- and Meta-Analyses of 137 895 Individuals.

PubMed

Wulff, Anders B; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2018-03-01

Loss-of-function mutations in APOC3 associate with low remnant cholesterol levels and low risk of ischemic vascular disease (IVD). Because some studies show an additional association with low levels of low-density lipoprotein cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of-function heterozygotes. We tested to what extent the low risk of IVD in APOC3 loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and LDL-C. In APOC3 loss-of-function heterozygotes versus noncarriers, we first determined remnant cholesterol and LDL-C levels in meta-analyses of 137 895 individuals. Second, we determined whether the association with LDL-C was masked by lipid-lowering therapy. Finally, using mediation analysis, we determined the fraction of the low risk of IVD and ischemic heart disease mediated by remnant cholesterol and LDL-C. In meta-analyses, remnant cholesterol was 43% lower (95% confidence interval, 40%-47%), and LDL-C was 4% lower (1%-6%) in loss-of-function heterozygotes (n=776) versus noncarriers. In the general population, LDL-C was 3% lower in loss-of-function heterozygotes versus noncarriers, 4% lower when correcting for lipid-lowering therapy, and 3% lower in untreated individuals ( P values, 0.06-0.008). Remnant cholesterol mediated 37% of the observed 41% lower risk of IVD and 54% of the observed 36% lower risk of ischemic heart disease; corresponding values mediated by LDL-C were 1% and 2%. The low risk of IVD observed in APOC3 loss-of-function heterozygotes is mainly mediated by the associated low remnant cholesterol and not by low LDL-C. Furthermore, the contribution of LDL-C to IVD risk was not masked by lipid-lowering therapy. This suggests APOC3 and remnant cholesterol as important new targets for reducing cardiovascular risk. © 2018 American Heart Association, Inc.

Association of blood polychlorinated biphenyls and cholesterol levels among Canadian Inuit.

PubMed

Singh, Kavita; Chan, Hing Man

2018-01-01

It has generally been thought that Inuit populations have low risk of cardiovascular disease due to high consumption of omega-3 fatty acids found in traditional marine-based diets. However, results of recent surveys showed that Inuit populations are experiencing increasing rates of cardiovascular disease and related risk factors. The purpose of this study was to investigate if blood polychlorinated biphenyls (PCBs) are associated with high cholesterol and related parameters in Canadian Inuit, known risk factors for cardiovascular disease. The Adult Inuit Health Survey (IHS, 2007-2008) included 2595 Inuit participants from three regions of the Canadian Arctic, of which 2191 could be classified as with or without high cholesterol. The high cholesterol outcome was defined by LDL-C > 3.36mmol/L or taking medication(s) that reduce cholesterol, and was examined in adjusted logistic regression models with individual blood levels of PCB congeners, sum of dioxin-like PCBs (∑DL-PCBs), or sum of non-dioxin-like PCBs (∑NDL-PCBs). Statistically significant covariates for high cholesterol were ranked in importance according to the proportion of the model log likelihood explained. Continuous clinical parameters of total cholesterol, triglycerides, LDL-C, and HDL-C were examined in multiple linear regression models with ∑DL-PCBs or ∑NDL-PCBs. A total of 719 participants had high cholesterol (32.8%). PCBs were associated with increased risk of high cholesterol, and higher levels of serum triglycerides, total cholesterol, and LDL-C. No association was observed between PCBs and serum HDL-C. With respect to other statistically significant covariates for high cholesterol, the log likelihood ranking of PCBs generally fell between body mass index (BMI) and age. Further work is needed to corroborate the associations observed with PCBs and lipids in Canadian Inuit and to examine if they are causal in the direction anticipated. Copyright © 2017 Elsevier Inc. All rights reserved.

21 CFR 101.62 - Nutrient content claims for fat, fatty acid, and cholesterol content of foods.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cholesterol content of foods. 101.62 Section 101.62 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Nutrient Content Claims § 101.62 Nutrient content claims for fat, fatty acid, and cholesterol content of foods. (a) General requirements. A claim about the level of fat, fatty acid, and cholesterol in a food...

9 CFR 381.462 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2011 CFR

2011-01-01

... acids, and cholesterol content. 381.462 Section 381.462 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.462 Nutrient content claims for fat, fatty acids, and cholesterol content. Link to... level of fat, fatty acid, and cholesterol in a product may only be made on the label or in labeling of...

9 CFR 317.362 - Nutrient content claims for fat, fatty acids, and cholesterol content.

Code of Federal Regulations, 2011 CFR

2011-01-01

... acids, and cholesterol content. 317.362 Section 317.362 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.362 Nutrient content claims for fat, fatty acids, and cholesterol content. Link to... level of fat, fatty acid, and cholesterol in a product may only be made on the label or in labeling of...

[Lipid profile from low socioeconomic level preschool children. Valencia, Venezuela].

PubMed

Solano, Liseti; Velásquez, Emma; Naddaf, Gloria; Páez, María

2003-01-01

Overweight and obesity are a public health problem worldwide affecting adults and children as well. The aim of this study was to assess overweight, lipid profile and cardiovascular risk ratios in 390 preschool children from low socio-economic level from Valencia, Venezuela. Nutritional anthropometric evaluation measured by body dimensions, and serum determination of cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and cardiovascular risk factors, were determined. 95% of the children were in relative and critical poverty. 14.3% of undernutrition and 20.8% of overweight was found. Lipid profile was in normal range, with no significant differences by sex, but higher values for HDL-cholesterol and risk ratios were found in children aged 1 to 3.99 years. Even though no differences were found by nutritional status, overweight children had higher values for lipids, except HDL-cholesterol. 6.3% of overweight children had cholesterol > or =170 mg/dL, 16.5% LDL-cholesterol > or =110 mg/dL, 40.5% triglycerides > or =75mg/dL and 100% HDL-cholesterol <45 mg/dL. Overweight and lipid profile alterations were present in an important group of the children, which increase their risk of obesity and chronic non-transmissible diseases. Nutritional and educational intervention should be addressed.

Introducing inducible fluorescent split cholesterol oxidase to mammalian cells.

PubMed

Chernov, Konstantin G; Neuvonen, Maarit; Brock, Ivonne; Ikonen, Elina; Verkhusha, Vladislav V

2017-05-26

Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments. The addition of rapamycin reconstituted a fluorescent enzyme, termed split GFP-COase, the fluorescence level of which correlated with its oxidation activity. A rapid decrease of cellular cholesterol induced by intracellular expression of the split GFP-COase promoted the dissociation of a cholesterol biosensor D4H from the plasma membrane. The process was reversible as upon rapamycin removal, the split GFP-COase fluorescence was lost, and cellular cholesterol levels returned to normal. These data demonstrate that the split GFP-COase provides a novel tool to manipulate cholesterol in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantum Iterative Deepening with an Application to the Halting Problem

PubMed Central

Tarrataca, Luís; Wichert, Andreas

2013-01-01

Classical models of computation traditionally resort to halting schemes in order to enquire about the state of a computation. In such schemes, a computational process is responsible for signaling an end of a calculation by setting a halt bit, which needs to be systematically checked by an observer. The capacity of quantum computational models to operate on a superposition of states requires an alternative approach. From a quantum perspective, any measurement of an equivalent halt qubit would have the potential to inherently interfere with the computation by provoking a random collapse amongst the states. This issue is exacerbated by undecidable problems such as the Entscheidungsproblem which require universal computational models, e.g. the classical Turing machine, to be able to proceed indefinitely. In this work we present an alternative view of quantum computation based on production system theory in conjunction with Grover's amplitude amplification scheme that allows for (1) a detection of halt states without interfering with the final result of a computation; (2) the possibility of non-terminating computation and (3) an inherent speedup to occur during computations susceptible of parallelization. We discuss how such a strategy can be employed in order to simulate classical Turing machines. PMID:23520465

Effects of dalcetrapib in patients with a recent acute coronary syndrome.

PubMed

Schwartz, Gregory G; Olsson, Anders G; Abt, Markus; Ballantyne, Christie M; Barter, Philip J; Brumm, Jochen; Chaitman, Bernard R; Holme, Ingar M; Kallend, David; Leiter, Lawrence A; Leitersdorf, Eran; McMurray, John J V; Mundl, Hardi; Nicholls, Stephen J; Shah, Prediman K; Tardif, Jean-Claude; Wright, R Scott

2012-11-29

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons). In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.).

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study

PubMed Central

Saravanan, A. V.; Ravishankar, P. L.; Kumar, Pradeep; Rajapandian, K.; Kalaivani, V.; Rajula, M. Prem Blaisie

2017-01-01

Aim: The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. Materials and Methods: This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. Results: There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. Conclusion: It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease. PMID:28462181

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study.

PubMed

Saravanan, A V; Ravishankar, P L; Kumar, Pradeep; Rajapandian, K; Kalaivani, V; Rajula, M Prem Blaisie

2017-01-01

The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease.

Cyclosporine A impairs the macrophage reverse cholesterol transport in mice by reducing sterol fecal excretion.

PubMed

Zanotti, Ilaria; Greco, Daniela; Lusardi, Giulia; Zimetti, Francesca; Potì, Francesco; Arnaboldi, Lorenzo; Corsini, Alberto; Bernini, Franco

2013-01-01

Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.

Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population.

PubMed

Bazzaz, J T; Nazari, M; Nazem, H; Amiri, P; Fakhrzadeh, H; Heshmat, R; Abbaszadeh, S; Amoli, M M

2010-01-01

Apolipoprotein E (APOE) is known as a major regulator of blood lipid levels in humans. A number of APOE gene allelic variants have been reported including E2, E3 and E4. Recent studies suggested a role for APOE in obesity and increased Body Mass Index (BMI) and plasma lipid levels in obese children. The aim of this study was to examine the association between APOE genetic variants and the BMI and lipid profile in an Iranian cohort. Samples were obtained from subjects who participated in a study based on the WHO-designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study for coronary artery disease risk assessment in Zone 17 of Tehran. The study was approved by the local ethical committee. Informed consent was obtained from all subjects included in this study. Subjects (n=320) were recruited. The level of triglyceride (TG) and total serum cholesterol was tested for all subjects in this study. Genotyping for APOE was carried using polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP)technique. Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8) software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. The frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2). The association found in this study between allele E2 and lower total cholesterol level had been reported in previous studies. We have also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with abnormal cholesterol (P=0.003 OR 2.4 95% CI; 1.3-4.6). Our data needs to be repeated in a larger population with more information for serum LDL and HDL levels and their subgroups.

Dalcetrapib and anacetrapib differently impact HDL structure and function in rabbits and monkeys[S

PubMed Central

Brodeur, Mathieu R.; Rhainds, David; Charpentier, Daniel; Mihalache-Avram, Teodora; Mecteau, Mélanie; Brand, Geneviève; Chaput, Evelyne; Perez, Anne; Niesor, Eric J.; Rhéaume, Eric; Maugeais, Cyrille; Tardif, Jean-Claude

2017-01-01

Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol (HDL-C) levels. However, the circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased HDL-C, raised small and large α-migrating HDL, and increased ABCA1-induced cholesterol efflux. In vervet monkeys, although anacetrapib produced similar results, dalcetrapib caused opposite effects because the LDL-C level was increased by 42% and HDL-C decreased by 48% (P < 0.01). The levels of α- and preβ-HDL were reduced by 16% (P < 0.001) and 69% (P < 0.01), resulting in a decrease of the serum cholesterol efflux capacity. CETPis modulate the plasma levels of mature and small HDL in vivo and consequently the cholesterol efflux capacity. The opposite effects of dalcetrapib in different species indicate that its impact on HDL metabolism could vary greatly according to the metabolic environment. PMID:28515138

Reemphasizing the Role of Exercise in Preventing Heart Disease.

ERIC Educational Resources Information Center

Nash, Heyward L.

1989-01-01

A recent study suggests that high-density lipoprotein cholesterol (HDL-C) level may be a better predictor of heart disease than total cholesterol level. Even moderate amounts of aerobic exercise can raise the level of HDL-C and lower the risk of coronary artery disease. (SM)

Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives.

PubMed

Guazzelli, Christina Aparecida Falbo; Lindsey, Prescilla Chow; de Araújo, Fabio Fernando; Barbieri, Márcia; Petta, Carlos Alberto; Aldrighi, Jose Mendes

2005-02-01

The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 microg ethinyl estradiol and 75 microg gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different.

Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of cholesterol metabolic pathway.

PubMed

Sen, S; Mukherjee, S

1997-01-01

Effect of unsaturated and saturated fats on cholesterol metabolism was studied in ascorbate sufficient and deficient guineapigs. Experimental animals were made chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver microsomal cytochrome P-450 level was found to be low in ascorbate deficient animals. Polyunsaturated fat intake could not lower the serum cholesterol level in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all over the world for its hypocholesterolemic effect. This study indicates that polyunsaturated fat intake with ascorbic acid deficiency may produce hypercholesterolemia.

Food Ingredients That Inhibit Cholesterol Absorption

PubMed Central

Jesch, Elliot D.; Carr, Timothy P.

2017-01-01

Cholesterol is a vital component of the human body. It stabilizes cell membranes and is the precursor of bile acids, vitamin D and steroid hormones. However, cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause atherosclerotic plaques within artery walls, leading to heart attacks and strokes. The efficiency of cholesterol absorption in the small intestine is of great interest because human and animal studies have linked cholesterol absorption with plasma concentration of total and low density lipoprotein cholesterol. Cholesterol absorption is highly regulated and influenced by particular compounds in the food supply. Therefore, it is desirable to learn more about natural food components that inhibit cholesterol absorption so that food ingredients and dietary supplements can be developed for consumers who wish to manage their plasma cholesterol levels by non-pharmacological means. Food components thus far identified as inhibitors of cholesterol absorption include phytosterols, soluble fibers, phospholipids, and stearic acid. PMID:28702423

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.

PubMed

Berghoff, Stefan A; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M; Saher, Gesine

2017-01-24

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

PubMed Central

Berghoff, Stefan A.; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K.; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M.; Saher, Gesine

2017-01-01

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes. PMID:28117328

The "Mevalonate hypothesis": a cholesterol-independent alternative for the etiology of atherosclerosis.

PubMed

Keizer, Hiskias G

2012-11-05

The "cholesterol hypothesis" is the leading theory to explain the cause of atherosclerosis. The "cholesterol hypothesis" assumes that plasma (LDL) cholesterol is an important causal factor for atherosclerosis.However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the "mevalonate hypothesis", assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis.Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels) in all these cases free radical production is observed as well as cardiovascular disease. Since in the "mevalonate hypothesis" cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria.In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This "mevalonate hypothesis" provides a better explanation for results obtained from recent clinical studies with cholesterol lowering drugs than the "cholesterol hypothesis". Furthermore, this hypothesis explains how cholesterol can be correlated with cardiovascular disease without being a causal factor for it. Finally it provides a logical explanation for the etiology of this disease.

Dietary protein level and origin (casein and highly purified soybean protein) affect hepatic storage, plasma lipid transport, and antioxidative defense status in the rat.

PubMed

Madani, S; Prost, J; Belleville, J

2000-05-01

The effects of different proportions (10, 20, and 30%) of dietary casein or highly purified soybean protein on lipid metabolism were studied in growing Wistar rats. Hepatic, plasma and lipoprotein lipid, and protein concentrations, plasma thiobarbituric acid-reactive substance (TBARS) levels, and resistance of red blood cells against free-radical attack were determined after a 4-wk dietary regimen. Compared with the 20% casein diet, the 20% soybean protein diet exhibited similar cholesterolemia but lower plasma triacylglycerol concentrations and very-low-density lipoprotein (VLDL) particle number, as measured by diminished contents of VLDL-triacylglycerol, VLDL-protein, and VLDL-apolipoprotein (Apo) B (B-100 and B-48). The soybean protein diet raised high-density lipoprotein (HDL)(2-3) particle number, as measured by enhanced concentrations of HDL(2-3) cholesterol, HDL-phospholipid, and HDL-ApoA-I. Increasing casein or soybean protein level (from 10 to 30%) in the diet involved higher VLDL-ApoB (B-100 and B-48), indicating an increase in the number of VLDL particles. Feeding the 30% casein or 30% soybean protein diet enhanced LDL-HDL(1) cholesterol contents. Despite similar HDL(2-3)-ApoA-I levels, the 30% casein diet enhanced the HDL(2-3) mass and its cholesterol concentrations. In contrast, feeding either the 10 or 30% soybean protein diet significantly lowered HDL(2-3) cholesterol and ApoA-I levels. These effects on cholesterol distribution in lipoprotein fractions occurred despite unchanged total cholesterol concentrations in plasma. Feeding 20% soybean protein versus 20% casein involved lower plasma TBARS concentrations. Decreasing casein or soybean protein levels in the diet were associated with higher plasma TBARS concentrations and had a lower resistance of red blood cells against free-radical attack. The present study shows that dietary protein level and origin play an important role in lipoprotein metabolism and the antioxidative defense status but do not affect total cholesterol concentrations in plasma.

A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: evaluation of the diabetes-accelerated atherosclerosis risk.

PubMed

Huang, Qilin; An, Yarui; Tang, Linlin; Jiang, Xiaoli; Chen, Hua; Bi, Wenji; Wang, Zhongchuan; Zhang, Wen

2011-11-30

In this paper, a novel dual enzymatic-biosensor is described for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the risk of diabetes-accelerated atherosclerosis. The biosensor was constructed by a three-step method. First, a poly-thionine (PTH) film was assembled on the surface of glassy carbon electrode by cyclic voltammetric electropolymerization of thionine, which serves as an electron transfer mediator (ETM). Second, gold nanoparticles (GNPs) were covered on the surface of PTH facilitating the electron transfer between glucose oxidase (GOx), cholesterol oxidase (ChOx) and electrode. Finally, the enzymes, GOx, cholesterol esterase (ChE), and ChOx, were covalently attached to the PTH layer through a chitosan (CH) linker. The PTH coupled with GNPs provides good selectivity, high sensitivity and little crosstalk for the dual enzymatic-biosensor. The developed biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibiting a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 μM, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 μM. The results of the diabetic mice demonstrated that the cholesterol level did not change obviously with the increase of glucose level in serum, while the cholesterol level was induced with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, which is the hallmark of early atherosclerosis. This study provides useful further evidences for the development of diabetes-accelerated atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of Rosuvastatin on the expression of the genes involved in cholesterol metabolism in rats: adaptive responses by extrahepatic tissues.

PubMed

Ahmadi, Yasin; Haghjoo, Amir Ghorbani; Dastmalchi, Siavoush; Nemati, Mahboob; Bargahi, Nasrin

2018-06-30

Statins mostly target the liver; therefore, increase in the synthesis of cholesterol by extra-hepatic tissues and then transferring this cholesterol to the liver can be regarded as adaptive responses by these tissues. In addition to cholesterol, these adaptive responses can increase isoprenoid units as the byproducts of the cholesterol biosynthesis pathway; isoprenoids play a key role in regulating cell signaling pathways and cancer development. Thus, there is a primary need for in vivo investigation of the effects of statins on the cholesterol metabolism in the extra-hepatic tissues. Eighteen male Sprague-Dawley rats were randomly divided into control (n = 9) and treatment (n = 9) groups. The treatment group was orally given 10 mg/kg/day of Rosuvastatin for 6 weeks. Then, serum lipid profile, expression levels of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), ABCA1, ABCG1 and ApoA1, and activity of HMGCR were measured in the liver, intestine and adipose tissues. Rosuvastatin significantly reduced total cholesterol and LDL-C. The expression levels of ABCA1, ABCG1, and ApoA1 in the liver and HMGCR in both liver and intestine were significantly increased in the Rosuvastatin treated-group. However, in the intestine, there were no significant differences in the expression levels of ABCA1 and ABCG1 between the study groups. Rosuvastatin had no effect on the adipose tissue. The HMGCR activity was significantly increased in the liver and intestine of the Rosuvastatin-treated group. In spite of the adipose tissue, the intestine efficiently responses to the reduced levels of cholesterol and increases its cholesterogenesis capacity. However, adipose tissue seems to play a small role in correcting cholesterol deficiency during the course of statin therapy. Copyright © 2018. Published by Elsevier B.V.

[Effect of decamethoxine, decamine and levorin on the content of cholesterol, phospholipids and triglycerides in albino rat liver].

PubMed

Kovtuniak, N A; Bordiakovskaia, L G; Stadniĭchuk, R F

1983-01-01

It has been shown in experiments that intramuscular injection of guaternary ammonium compounds (decamethoxine and decamine) and levorin changed the content of cholesterol, phospholipids and triglycerides in the liver of white rats. Decamethoxine decreased the content of phospholipids and cholesterol and raised the concentration of triglycerides. Decamine decreased the level of phospholipids and raised the content of cholesterol and triglycerides, while levorin minimized the content of phospholipids, cholesterol and triglycerides.

Lack of effect of dietary fiber on serum lipids, glucose, and insulin in healthy young men fed high starch diets.

PubMed

Ullrich, I H; Albrink, M J

1982-07-01

Eight healthy young men were fed a 72% carbohydrate high starch diet either high or low in dietary fiber for 4 days in a double cross-over design. Both groups showed a slight transient increase in plasma triglyceride level and a decrease in total and high-density lipoprotein cholesterol. There were few differences in glucose and insulin levels after glucose and meal tolerance tests after each diet. Fasting triglycerides and high-density lipoprotein cholesterol were inversely related at base-line; insulin response to oral glucose was inversely related to high-density lipoprotein cholesterol levels at the end of the study. We conclude that a high carbohydrate high starch diet, whether high or low in fiber, caused little increase in triglycerides, with little difference between the high and low fiber diets. Dietary fiber did not influence the fall in plasma cholesterol or high-density lipoprotein cholesterol concentrations over and above that seen after the low fiber diet.

Amyloid precursor protein controls cholesterol turnover needed for neuronal activity

PubMed Central

Pierrot, Nathalie; Tyteca, Donatienne; D'auria, Ludovic; Dewachter, Ilse; Gailly, Philippe; Hendrickx, Aurélie; Tasiaux, Bernadette; Haylani, Laetitia El; Muls, Nathalie; N'Kuli, Francisca; Laquerrière, Annie; Demoulin, Jean-Baptiste; Campion, Dominique; Brion, Jean-Pierre; Courtoy, Pierre J; Kienlen-Campard, Pascal; Octave, Jean-Noël

2013-01-01

Perturbation of lipid metabolism favours progression of Alzheimer disease, in which processing of Amyloid Precursor Protein (APP) has important implications. APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid homeostasis. Here, we investigated whether up or down regulation of full-length APP expression affected neuronal lipid metabolism. Expression of APP decreased HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA levels, while its down regulation had opposite effects. APP and SREBP1 co-immunoprecipitated and co-localized in the Golgi. This interaction prevented Site-2 protease-mediated processing of SREBP1, leading to inhibition of transcription of its target genes. A GXXXG motif in APP sequence was critical for regulation of HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover, leading to inhibition of neuronal activity, which was rescued by geranylgeraniol, generated in the mevalonate pathway, in both APP expressing and mevastatin treated neurons. We conclude that APP controls cholesterol turnover needed for neuronal activity. PMID:23554170

Nutrigenetics of cholesterol metabolism: observational and dietary intervention studies in the postgenomic era.

PubMed

Abdullah, Mohammad M H; Jones, Peter J H; Eck, Peter K

2015-08-01

Cholesterol metabolism is a well-defined responder to dietary intakes and a classic biomarker of cardiovascular health. For this reason, circulating cholesterol levels have become key in shaping nutritional recommendations by health authorities worldwide for better management of cardiovascular disease, a leading cause of mortality and one of the most costly health problems globally. Data from observational and dietary intervention studies, however, highlight a marked between-individual variability in the response of cholesterol metabolism to similar dietary protocols, a phenomenon linked to genetic heterogeneity. This review summarizes the postgenomic evidence of polymorphisms within cholesterol-associated genes relative to fasting circulating cholesterol levels under diverse nutritional conditions. A number of cholesterol-related gene-diet interactions are confirmed, which may have clinical importance, supporting a deeper look into the rapidly emerging field of nutrigenetics for meaningful conclusions that may eventually lead to genetically targeted dietary recommendations in the era of personalized nutrition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Photonic modulation of EGFR: 280nm low level light arrests cancer cell activation and migration

NASA Astrophysics Data System (ADS)

Botelho, Cláudia M.; Marques, Rogério; Viruthachalam, Thiagarajan; Gonçalves, Odete; Vorum, Henrik; Gomes, Andreia C.; Neves-Petersen, Maria Teresa

2017-02-01

Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.

Epidemiology as a Guide to Clinical Decisions—II. Diet and Coronary Heart Disease

PubMed Central

Hulley, Stephen B.; Sherwin, Roger; Nestle, Marion; Lee, Philip R.

1981-01-01

Should clinicians prescribe fat-controlled diets to prevent coronary heart disease (CHD), and, if so, which patients should be given this advice? In this report, we use a three-step model to explain the hypothesis that dietary fats are a cause of CHD: dietary saturated fat and cholesterol raise serum cholesterol levels (step 1), which are a cause of subclinical coronary atherosclerosis (step 2), and, in turn, clinically manifest CHD (step 3). An evaluation of the scientific evidence for each step leads us to conclude that dietary fats definitely influence the level of serum cholesterol, and that serum cholesterol is probably a cause of atherosclerosis and CHD. To determine the clinical implications, we examined the potential of various foods to keep cholesterol levels lower, as well as the projected magnitude of reduction in CHD risk. The likelihood of benefit varies among patients, ranging from uncertain or trivial (for those with lower serum cholesterol levels, those who are free of other risk factors and the elderly) to substantial (for patients with higher serum cholesterol levels, those who have other risk factors and those who are young). This analysis supports an individualized approach to clinical management; each decision to prescribe a fat-controlled diet should be a judgment that depends on art—the therapeutic philosophy of each clinician and the particular needs of each patient—as well as on science. The implication for public health policies is that they should promote rather than a uniform eating pattern for all Americans, a uniform environment that enhances individual choices. This should include efforts to educate the medical profession and the public, and more comprehensive and informative foodlabeling practices. PMID:7257376

Anti-atherogenic effect of chromium picolinate in streptozotocin-induced experimental diabetes.

PubMed

Sundaram, Bhuvaneshwari; Singhal, Kirti; Sandhir, Rajat

2013-03-01

Several studies have implicated changes in the levels of trace elements in diabetes. Chromium is one such element that seems to potentiate insulin action, thereby regulating carbohydrate and lipid metabolism. The aim of the present study was to evaluate the effect of chromium supplementation as chromium picolinate on the lipid profile of streptozotocin (STZ)-induced diabetic rats. Rats were rendered diabetic by a single injection of STZ (50 mg/kg, i.p.). Chromium picolinate (1 mg/kg per day, p.o.) was administered to rats for a period of 4 weeks. At the end of the treatment period, plasma total lipids, triglycerides, total cholesterol and lipoprotein levels were determined, as was hepatic glucose-6-phosphate dehydrogenase activity. Total plasma lipids increased significantly in diabetic rats and this increase was ameliorated by chromium treatment for 4 weeks. Elevated total lipids in diabetic rats were due to increased plasma triglyceride and cholesterol levels. Chromium supplementation lowered plasma triglyceride and cholesterol levels to near normal. Chromium treatment also normalized low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol levels and improved the total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and HDL-C:LDL-C ratios, suggesting an anti-atherogenic effect. In addition to improving the plasma lipid profile, chromium supplementation normalized liver glucose-6-phosphate dehydrogenase activity in diabetic rats. These results provide evidence that chromium picolinate effectively attenuates the dyslipidemia associated with diabetes and thus can be used as an adjuvant therapy in the treatment of diabetes and its associated complications. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

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

PubMed

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

2010-04-30

Mass spectrometric imaging has been utilized to localize individual astrocytes and to obtain cholesterol populations at the single-cell level in laser desorption ionization (LDI) with colloidal silver. The silver ion adduct of membrane-bound cholesterol was monitored to detect individual cells. Good correlation between mass spectrometric and optical images at different cell densities indicates the ability to perform single-cell studies of cholesterol abundance. The feasibility of quantification is confirmed by the agreement between the LDI-MS ion signals and the results from a traditional enzymatic fluorometric assay. We propose that this approach could be an effective tool to study chemical populations at the cellular level. Published in 2010 by John Wiley & Sons, Ltd.

Posttesticular sperm maturation, infertility, and hypercholesterolemia

PubMed Central

Whitfield, Marjorie; Pollet-Villard, Xavier; Levy, Rachel; Drevet, Joël R; Saez, Fabrice

2015-01-01

Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia) affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa. PMID:26067871

Small, qualitative changes in fatty acid intake decrease plasma low-density lipoprotein-cholesterol levels in mildly hypercholesterolemic outpatients on their usual high-fat diets.

PubMed

Lecerf, Jean-Michel; Luc, Gérald; Marécaux, Nadine; Bal, Sylvie; Bonte, Jean-Paul; Lacroix, Brigitte; Cayzeele, Amélie

2009-01-01

The diet is the first step in managing hypercholesterolemia. The objective of the present study is to assess whether moderate changes in dietary fatty acids improve plasma lipid parameters in mildly hypercholesterolemic outpatients. Using a randomized double-blind study, 121 outpatients within two groups received an isocaloric amount of unsaturated margarine or butter. Clinical and anthropometric measurements and a 3-day food record were made. Chi-square and Fisher's tests were used to compare qualitative variables and the general linear procedure was used to compare the groups. Additional analyses were performed after adjustment. There was a significant difference (P <0.03) in low-density lipoprotein-cholesterol levels between the groups. Total cholesterol, low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol and apolipoprotein B values decreased in the unsaturated group in comparison with the saturated group. Low-density lipoprotein-cholesterol changes were correlated with the variation in polyunsaturated fatty acid intake and with plasma phospholipid linoleic acid levels. A small change in saturated by polyunsaturated fatty acid intake may improve plasma lipid parameters in mildly hypercholesterolemic subjects.

Envelope lipid-packing as a critical factor for the biological activity and stability of alphavirus particles isolated from mammalian and mosquito cells.

PubMed

Sousa, Ivanildo P; Carvalho, Carlos A M; Ferreira, Davis F; Weissmüller, Gilberto; Rocha, Gustavo M; Silva, Jerson L; Gomes, Andre M O

2011-01-21

Alphaviruses are enveloped arboviruses. The viral envelope is derived from the host cell and is positioned between two icosahedral protein shells (T = 4). Because the viral envelope contains glycoproteins involved in cell recognition and entry, the integrity of the envelope is critical for the success of the early events of infection. Differing levels of cholesterol in different hosts leads to the production of alphaviruses with distinct levels of this sterol loaded in the envelope. Using Mayaro virus, a New World alphavirus, we investigated the role of cholesterol on the envelope of alphavirus particles assembled in either mammalian or mosquito cells. Our results show that although quite different in their cholesterol content, Mayaro virus particles obtained from both cells share a similar high level of lateral organization in their envelopes. This organization, as well as viral stability and infectivity, is severely compromised when cholesterol is depleted from the envelope of virus particles isolated from mammalian cells, but virus particles isolated from mosquito cells are relatively unaffected by cholesterol depletion. We suggest that it is not cholesterol itself, but rather the organization of the viral envelope, that is critical for the biological activity of alphaviruses.

Cholesterol homeostasis: How do cells sense sterol excess?

PubMed

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model.

PubMed

Littleton, Robert M; Miller, Matthew; Hove, Jay R

2012-07-23

Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4-30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model. Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output. In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P < 0.05, Student's t-test). We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w) high cholesterol diet-treated cardiac output significant at P < 0.05, 1-way ANOVA). Using this model, we found hawthorn leaves and flowers significantly reduce intravascular cholesterol levels (P < 0.05, 1-way ANOVA) and interact with cholesterol to impact cardiac output in hypercholesterolemic fish (2-way ANOVA, P < 0.05 for interaction effect). The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels. Further, our observation that hawthorn leaves and flowers interact with cholesterol to impact cardiac output indicates that the physiological effects of hawthorn may depend on diet.

A novel role for CRTC2 in hepatic cholesterol synthesis through SREBP‐2

PubMed Central

Li, Yujie; Song, Yongfeng; Zhao, Meng; Guo, Yanjing; Yu, Chunxiao; Chen, Wenbin; Shao, Shanshan; Xu, Chao; Zhou, Xinli; Zhao, Lifang; Zhang, Zhenhai; Bo, Tao; Xia, Yu; Proud, Christopher G.; Wang, Xuemin; Wang, Li; Zhao, Jiajun

2017-01-01

Cholesterol synthesis is regulated by the transcription factor sterol regulatory element binding protein 2 (SREBP‐2) and its target gene 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR), which is the rate‐limiting enzyme in cholesterol synthesis. Cyclic adenosine monophosphate–responsive element (CRE) binding protein–regulated transcription coactivator (CRTC) 2 is the master regulator of glucose metabolism. However, the effect of CRTC2 on cholesterol and its potential molecular mechanism remain unclear. Here, we demonstrated that CRTC2 expression and liver cholesterol content were increased in patients with high serum cholesterol levels who underwent resection of liver hemangiomas, as well as in mice fed a 4% cholesterol diet. Mice with adenovirus‐mediated CRTC2 overexpression also showed elevated lipid levels in both serum and liver tissues. Intriguingly, hepatic de novo cholesterol synthesis was markedly increased under these conditions. In contrast, CRTC2 ablation in mice fed a 4% cholesterol diet (18 weeks) showed decreased lipid levels in serum and liver tissues compared with those in littermate wild‐type mice. The expression of lipogenic genes (SREBP‐2 and HMGCR) was consistent with hepatic CRTC2 levels. In vivo imaging showed enhanced adenovirus‐mediated HMGCR‐luciferase activity in adenovirus‐mediated CRTC2 mouse livers; however, the activity was attenuated after mutation of CRE or sterol regulatory element sequences in the HMGCR reporter construct. The effect of CRTC2 on HMGCR in mouse livers was alleviated upon SREBP‐2 knockdown. CRTC2 modulated SREBP‐2 transcription by CRE binding protein, which recognizes the half‐site CRE sequence in the SREBP‐2 promoter. CRTC2 reduced the nuclear protein expression of forkhead box O1 and subsequently increased SREBP‐2 transcription by binding insulin response element 1, rather than insulin response element 2, in the SREBP‐2 promoter. Conclusion: CRTC2 regulates the transcription of SREBP‐2 by interfering with the recognition of insulin response element 1 in the SREBP‐2 promoter by forkhead box O1, thus inducing SREBP‐2/HMGCR signaling and subsequently facilitating hepatic cholesterol synthesis. (Hepatology 2017;66:481–497). PMID:28395113

Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes-The Update.

PubMed

Maekawa, Masashi

2017-03-03

The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking) in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine). Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4) of Perfringolysin O (PFO, theta toxin), a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling

PubMed Central

Wasser, Catherine R; Ertunc, Mert; Liu, Xinran; Kavalali, Ege T

2007-01-01

Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-β-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-β-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis. PMID:17170046

High density lipoprotein cholesterol is associated with serum cortisol in older people.

PubMed

Varma, V K; Rushing, J T; Ettinger, W H

1995-12-01

To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people. A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS). A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina. Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound. Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes. Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.

Achievement of cholesterol targets and prescribing of higher-cost statins: a cross-sectional study in general practice.

PubMed

Fleetcroft, Robert; Schofield, Peter; Duerden, Martin; Ashworth, Mark

2012-12-01

There is conflicting evidence as to whether achievement of cholesterol targets at the population level is dependent on the choice and cost of statin. To investigate the practice-level relationship between cholesterol quality indicators in patients with heart disease, stroke, and diabetes and prescribing of low-cost statins. Correlations and linear regression modelling of retrospective cross-sectional practice-level data with potential explanatory variables in 7909 (96.4%) general practices in England in 2008-2009. Quality indicator data were obtained from the Information Centre and prescribing data from the NHS Business Authority. A 'cholesterol quality indicator' score was constructed by dividing the numbers of patients achieving the target for cholesterol control of ≤5 mmol/l in stroke, diabetes, and heart disease by the numbers on each register. A 'low-cost statin' ratio score was constructed by dividing the numbers of defined daily doses of simvastatin and pravastatin by the total numbers of defined daily doses of statins. Simvastatin accounted for 83.3% (standard deviation [SD] = 15.7%) of low-cost statins prescribed and atorvastatin accounted for 85.7% (SD = 14.8%) of high-cost statins prescribed. The mean cholesterol score was 73.7% (SD = 6.0%). Practices using a higher proportion of the low-cost statins were less successful in achieving cholesterol targets. An increase of 10% in the prescribing of low-cost statins was associated with a decrease of 0.46% in the cholesterol quality indicator score (95% confidence interval = -0.54% to -0.38%, P<0.001). Greater use of low-cost statins was associated with a small reduction in cholesterol control.

Cholesterol complacency in Australia: time to revisit the basics of cardiovascular disease prevention.

PubMed

Carrington, Melinda J; Retegan, Claudia; Johnston, Colin I; Jennings, Garry L; Stewart, Simon

2009-03-01

Community awareness of the importance of hypercholesterolemia and the need for appropriate therapy is an important part of global efforts to reduce the population burden of cardiovascular disease. The aim of this study was to assess the knowledge and attitudes about cholesterol and to determine adherence to taking cholesterol-lowering medication among patients at high risk for cardiovascular events. In spite of the availability of lifestyle and medical treatments for lipid management, an estimated 50% of adult Australians (6.4 million) remain at risk for a cardiovascular-related event because they have total blood cholesterol levels which exceed recommended limits. It is within this context that a significant gap remains in meeting cholesterol goals, despite easy to meet targets with readily available therapeutic options. A two-page national self-report postal survey was conducted from August-October 2006. A total of 508 Australian adults previously treated for hypercholesterolemia were surveyed to determine their understanding about cholesterol and their adherence to treatment. The mean age of participants was 67 (SD 10) years (72% male). Many participants (72%) were at risk of a cardiovascular event based on a prior history and 18% had type II diabetes. Participants had been prescribed lipid-lowering therapy (94% statin therapy) for an average of 10 years and visited their general practitioner on average three times per year. For those who knew their most recent cholesterol reading (67%), the total cholesterol was on average 4.5 (SD 1.1) mmol/l. This level was above the recommended limits for 40% of participants. Overall, 85% of participants reported knowing that there was high- and low-density lipoprotein forms of cholesterol, but only 56% and 38%, respectively, said that they understood or showed signs of clearly understanding the different types of cholesterol when their knowledge was assessed further. On the whole, therefore, participants had a limited understanding about cholesterol and its potential impact on cardiovascular events. Moreover, 25% of participants admitted to being non-compliant in taking their medication and only 51% correctly identified modifiable risk factors as most important for heart disease. Encouragingly, despite 85% of participants finding lifestyle changes challenging, most still identified their potential benefits. This study highlights that there are many unresolved issues in relation to educating high-risk patients who regularly visit their general practitioner to learn about and optimise their cholesterol levels via appropriate treatment and monitoring. There is a need for urgent public education and management by individuals and the health community. Strategies to address 'cholesterol complacency', in the sense of a willingness to accept sub-optimal standards of cholesterol control at both the patient and healthcare system levels (general practitioners in particular), are urgently needed to truncate an anticipated rising tide of cardiovascular disease in Australia.

Application of short message service to control blood cholesterol: a field trial.

PubMed

Sadeghian, Saeed; Shams, Mohsen; Alipour, Zahra; Saadat, Soheil; Hamidian, Reza; Shahrzad, Maryam

2017-03-28

Despite recommendations, many middle-age adults neglect to check their blood cholesterol levels. Short message service (SMS, also known as texting) has been seldom studied for preventive education. We estimated how SMS can be a cost-effective method in encouraging people to check their blood cholesterol levels. In a field trial, 3600 cell phone users (age > 30) were randomly assigned to the intervention (N: 1200) and the control groups (N: 2400). An SMS was sent to the intervention group for five rounds every two weeks, which targeted the cognitive and affective learning and finally advised the blood cholesterol level to be checked, if not checked during the past twelve months. Two weeks after the last round, both groups were asked for the time/level of their latest blood cholesterol, family history of early cardiac death and having a family member with coronary heart disease (CHD), and to report their attitude about whether annual blood sampling is worth the cost and time to prevent CHD. Moreover, the intervention group was asked if they remembered the SMS content. The cost-effectiveness was evaluated by estimating the "number needed to treat" (NNT) and calculating the cost of sending SMS to that number of people. In the intervention group, 629 individuals (72.0%) recalled the SMS content. The factors associated with cholesterol screening during the past two years were older age, diabetes, family history of coronary disease, higher education, female gender and being non-smoker. In both groups, women were significantly more aware of their blood cholesterol level (68.7% vs. 53.6%). The relative frequency of respondents who believed it was not worth checking their cholesterol annually was significantly lower in the intervention group (P < 0.001). The intervention group was significantly more likely to check its blood cholesterol levels (OR:1.22) after adjustment for age, diabetes, family history of CHD and smoking. The NNT was estimated ≈ 25 for the general population and ≈ 11 for those who received SMS and had a family member with CHD. We would postulate that SMS could affect people's adherence to preventive programs. Relatives of patients admitted with a diagnosis of CHD should be prioritized for superior cost-effectiveness and logistical feasibility.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

PubMed

Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

2017-09-28

Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).

Excess cholesterol inhibits glucose-stimulated fusion pore dynamics in insulin exocytosis.

PubMed

Xu, Yingke; Toomre, Derek K; Bogan, Jonathan S; Hao, Mingming

2017-11-01

Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β-cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β-cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β-cells and contribute to β-cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β-cell function remain largely unknown. Here, we used total internal reflection fluorescence microscopy to address, at the single-granule level, the role of cholesterol in regulating fusion pore dynamics during insulin exocytosis. We focused particularly on the effects of cholesterol overload, which is relevant to type 2 diabetes. We show that excess cholesterol reduced the number of glucose-stimulated fusion events, and modulated the proportion of full fusion and kiss-and-run fusion events. Analysis of single exocytic events revealed distinct fusion kinetics, with more clustered and compound exocytosis observed in cholesterol-overloaded β-cells. We provide evidence for the involvement of the GTPase dynamin, which is regulated in part by cholesterol-induced phosphatidylinositol 4,5-bisphosphate enrichment in the plasma membrane, in the switch between full fusion and kiss-and-run fusion. Characterization of insulin exocytosis offers insights into the role that elevated cholesterol may play in the development of type 2 diabetes. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Association between non-high-density lipoprotein cholesterol concentrations and mortality from coronary heart disease among Japanese men and women: the Ibaraki Prefectural Health Study.

PubMed

Noda, Hiroyuki; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Ohtaka, Emiko; Ohta, Hitoshi

2010-02-01

The aim of this study was to examine whether non-high-density lipoprotein cholesterol (non-HDL-cholesterol) raises the risk of coronary heart disease in a dose-response fashion in a non-obese population with low total cholesterol levels and high HDL-cholesterol levels, such as Japanese. A total of 30,802 men and 60,417 women, aged 40 to 79 years with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance through 2003 identified 539 coronary heart disease deaths. The mean values for non-HDL-cholesterol were 140 mg/dL for men and 151 mg/dL for women. The corresponding mean values were 193 mg/dL and 208 mg/dL total cholesterol and 52 mg/dL and 57 mg/dL HDL-cholesterol, respectively. Men with non-HDL-cholesterol > or = 180 mg/dL had a two-fold higher age-adjusted risk of mortality from coronary heart disease than did those with non-HDL-cholesterol <100 mg/dL, whereas no such association was found for women. The multivariable hazard ratio for > or = 180 mg/dL versus <100 mg/dL of non-HDL-cholesterol was 2.22 (95% confidence interval: 1.37 to 3.62) for men and 0.71 (0.37 to 1.34) for women. Higher concentrations of non-HDL-cholesterol were associated with an increased risk of mortality from coronary heart disease for men, but not for women.

Ambient and at-the-ear occupational noise exposure and serum lipid levels.

PubMed

Arlien-Søborg, Mai C; Schmedes, Astrid S; Stokholm, Z A; Grynderup, M B; Bonde, J P; Jensen, C S; Hansen, Å M; Frederiksen, T W; Kristiansen, J; Christensen, K L; Vestergaard, J M; Lund, S P; Kolstad, H A

2016-10-01

Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels. This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear. Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors. No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.

Lactobacillus acidophilus K301 Inhibits Atherogenesis via Induction of 24 (S), 25-Epoxycholesterol-Mediated ABCA1 and ABCG1 Production and Cholesterol Efflux in Macrophages

PubMed Central

Kim, Hye Sun; Park, Woo Jung; Kim, Joo-Yun; Chung, Dae Kyun

2016-01-01

Lactobacillus acidophilus species are well-known probiotics with the beneficial activity of regulating cholesterol levels. In this study, we showed that L. acidophilus K301 reduced the level of cholesterol through reverse transport in macrophages. L. acidophilus K301 upregulated the mRNA and protein levels of genes such as ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) under the control of liver X receptor (LXR), resulting in increased apoA-I-dependent cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. L. acidophilus K301 induced both ABCA1 and ABCG1 through the endogenous LXR agonist 24(S), 25-epoxcycholesterol, which is synthesized by intracellular cholesterol synthetic pathways. In vivo studies using L. acidophilus K301-treated ApoE-/- mice showed reduced accumulation of lipoproteins in the arterial lumen. The inhibitory effects of L. acidophilus K301 on accumulation of lipoprotein in atherosclerotic plaques were mediated by the induction of squalene reductase (SQLE) and oxidosqualene cyclase (OSC) and resulted in ABCA1-mediated cholesterol efflux. Taken together, our findings revealed that Lactobacillus acidophilus K301 regulates the expression of genes related to cholesterol reverse transport via the induction of endogenous LXR agonist, suggesting the therapeutic potential of Lactobacillus acidophilus K301 as an anti-atherosclerotic agent. PMID:27120199

Lactobacillus acidophilus K301 Inhibits Atherogenesis via Induction of 24 (S), 25-Epoxycholesterol-Mediated ABCA1 and ABCG1 Production and Cholesterol Efflux in Macrophages.

PubMed

Hong, Yi-Fan; Kim, Hangeun; Kim, Hye Sun; Park, Woo Jung; Kim, Joo-Yun; Chung, Dae Kyun

2016-01-01

Lactobacillus acidophilus species are well-known probiotics with the beneficial activity of regulating cholesterol levels. In this study, we showed that L. acidophilus K301 reduced the level of cholesterol through reverse transport in macrophages. L. acidophilus K301 upregulated the mRNA and protein levels of genes such as ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) under the control of liver X receptor (LXR), resulting in increased apoA-I-dependent cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. L. acidophilus K301 induced both ABCA1 and ABCG1 through the endogenous LXR agonist 24(S), 25-epoxcycholesterol, which is synthesized by intracellular cholesterol synthetic pathways. In vivo studies using L. acidophilus K301-treated ApoE-/- mice showed reduced accumulation of lipoproteins in the arterial lumen. The inhibitory effects of L. acidophilus K301 on accumulation of lipoprotein in atherosclerotic plaques were mediated by the induction of squalene reductase (SQLE) and oxidosqualene cyclase (OSC) and resulted in ABCA1-mediated cholesterol efflux. Taken together, our findings revealed that Lactobacillus acidophilus K301 regulates the expression of genes related to cholesterol reverse transport via the induction of endogenous LXR agonist, suggesting the therapeutic potential of Lactobacillus acidophilus K301 as an anti-atherosclerotic agent.

Physical activity, sedentary behavior time and lipid levels in the Observation of Cardiovascular Risk Factors in Luxembourg study.

PubMed

Crichton, Georgina E; Alkerwi, Ala'a

2015-08-11

Recently attention has been drawn to the health impacts of time spent engaging in sedentary behaviors. While many studies have investigated general physical activity (PA) in relation to blood lipid levels, the current study aimed to examine the intensity of activity, including sedentary behavior time, and time spent engaging in moderate and intense PA, with concentrations of HDL and LDL-cholesterol, total cholesterol, and triglycerides. Participants comprised 1331 individuals, aged 18 to 70 years, from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study, who underwent objective cardiovascular health assessments and completed the International Physical Activity Questionnaire (IPAQ). Time spent engaging in sedentary behaviors (screen time on a workday and a day off, and total sitting time on a work day), and moderate and intense PA, were related to levels of HDL and LDL-cholesterol, total cholesterol, and triglycerides. Analyses were conducted in the whole sample, and then with stratification according to BMI (normal weight versus overweight/obese). Both lower screen time during days off and higher intense PA time were significantly associated with higher HDL-cholesterol after full adjustment for socio-demographic factors, dietary factors and smoking (both p < 0.05). In normal weight individuals, consistent positive relations between triglycerides, LDL, and total cholesterol with all sedentary behavior time variables were observed (all p < 0.05; adjusted for age, education, gender). There were no statistically significant associations between any intensity level of PA or sedentary behavior time variable and lipid levels in those overweight or obese. Spending less time in sedentary behaviors, and engaging in medium levels of intense physical activity may be associated with a more favorable blood lipid profile, particularly with regard to levels of HDL and triglycerides.

Consumption of Probiotic Lactobacillus fermentum MTCC: 5898-Fermented Milk Attenuates Dyslipidemia, Oxidative Stress, and Inflammation in Male Rats Fed on Cholesterol-Enriched Diet.

PubMed

Yadav, Radha; Khan, Suhail Hakeem; Mada, Sanusi Bello; Meena, Sunita; Kapila, Rajeev; Kapila, Suman

2018-05-13

There is a growing and alarming prevalence that increased serum cholesterol is closely related to increased cardiovascular disease risk. Probiotic consumption could be a safe and natural strategy to combat. Therefore, we sought to examine the cholesterol-lowering potential of co-supplementation of probiotic bacteria Lactobacillus fermentum MTCC: 5898-fermented buffalo milk (2.5% fat) in rats fed cholesterol-enriched diet. Male Wistar rats were divided into three groups on the basis of feed, viz. group 1, fed standard diet (SD); group 2, fed cholesterol-enriched diet (CED); and group 3, fed cholesterol-enriched diet along with L. fermentum MTCC: 5898-fermented milk (CED+LF) for 90 days. At the endpoint, significantly higher levels of serum total cholesterol, low-density lipoprotein cholesterol, triacylglycerols, very low density lipoprotein cholesterol, atherogenic index, coronary artery risk index, hepatic lipids, lipid peroxidation, and mRNA expression of inflammatory cytokines (TNF-α and IL-6) in the liver while significantly lower levels of serum high-density lipoprotein cholesterol and anti-oxidative enzyme activities, catalase, superoxide dismutase, and glutathione peroxidase in the liver and kidney were observed in the CED group compared to the SD group. Compared to the CED group, these adverse physiological alterations were found significantly improved in the CED+LF group. Hence, this study proposes that L. fermentum MTCC: 5898 is a potential probiotic bacteria that can be consumed to tackle hypercholesterolemia. Graphical Abstract ᅟ.

Interaction between statin use and saturated fat intake in relation to cognitive test performance

USDA-ARS?s Scientific Manuscript database

Strokes, microvascular disease, and Alzheimer’s disease adversely affect cognitive function in older people. High circulating cholesterol levels and amyloid-beta peptide deposition contribute to these conditions. Statins lower serum cholesterol by interfering with cholesterol biosynthesis, and they ...

Influence of biological factors on lipid and fibrinogen measurements in young men. An epidemiological study in 2009 recruits.

PubMed

Pitsavos, C; Skoumas, J; Dernellis, J; Toutouza, M; Doulalas, A; Stefanadis, C; Toutouzas, P

1998-11-01

The aim of the present study was to detect significant relationships between lipid and fibrinogen measurements and several biological factors in young men. Medical history was obtained, and plasma lipids, lipoprotein (a) and fibrinogen levels were measured in 2009 male Greek army recruits (mean age 22.37+/-3.03 years) not taking any drugs. Plasma levels were as follows: total cholesterol, 171+/-34 mg x dl(-1), low density lipoprotein (LDL) cholesterol, 111+/-34 mg x dl(-1), high density lipoprotein (HDL) cholesterol, 45+/-10 mg x dl(1), and triglycerides, 74+/-32 mg x dl(-1). Lipoprotein (a) and fibrinogen were 18+/-13 and 278+/-67 mg x dl(-1). The atherosclerotic index, calculated as the ratio of total cholesterol/HDL, was 4+/-1. Analysis of multivariate models that included potentially confounding factors revealed the following: body mass index, season of year during which blood examinations were performed, alcohol consumption, and place of residence were found to be significantly associated with plasma levels of total cholesterol, LDL-cholesterol, fibrinogen and the atherosclerotic index in the pooled population. Season and physical activity were significantly associated with HDL-cholesterol, whereas season and family history of acute myocardial infarction were associated with triglycerides levels. Body mass index, family history of myocardial infarction and physical activity were associated with lipoprotein (a). Body mass index, season, alcohol consumption and place of residence are markers of plasma lipid profile and fibrinogen in young men. A family history of acute myocardial infarction and physical activity are related to lipoprotein (a).

Characterization of starter kimchi fermented with Leuconostoc kimchii GJ2 and its cholesterol-lowering effects in rats fed a high-fat and high-cholesterol diet.

PubMed

Jo, Se Yeon; Choi, Eun A; Lee, Jae Joon; Chang, Hae Choon

2015-10-01

The hypocholesterolemic effects of lactic acid bacteria and kimchi have been demonstrated previously. However, the kimchi fermentation process still relies on naturally present microorganisms. To obtain functional kimchi with consistent quality, we validated the capacity of Leuconostoc kimchii GJ2 as a starter culture to control kimchi fermentation. Moreover, cholesterol-lowering effects of starter kimchi as a health-promoting product were explored. Bacteriocin production by Lc. kimchii GJ2 was highly enhanced in the presence of 5% Lactobacillus sakei NJ1 cell fractions. When kimchi was fermented with bacteriocin-enhanced Lc. kimchii GJ2, Lc. kimchii GJ2 became overwhelmingly predominant (98.3%) at the end of fermentation and maintained its dominance (up to 82%) for 84 days. Growing as well as dead cells of Lc. kimchii GJ2 showed high cholesterol assimilation (in vitro). Rats were fed a high-fat and high-cholesterol diet supplemented with starter kimchi. The results showed that feeding of starter kimchi significantly reduced serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels. Additionally, atherogenic index, cardiac risk factor and triglyceride and total cholesterol levels in liver and epididymal adipose tissue decreased significantly in rats fed starter kimchi. Kimchi fermented with Lc. kimchii GJ2 as a starter culture has efficient cholesterol-lowering effects. © 2014 Society of Chemical Industry.

2-heptyl-formononetin increases cholesterol and induces hepatic steatosis in mice.

PubMed

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.

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

PubMed Central

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

Aerobic exercise improves reverse cholesterol transport in cholesteryl ester transfer protein transgenic mice.

PubMed

Rocco, D D F M; Okuda, L S; Pinto, R S; Ferreira, F D; Kubo, S K; Nakandakare, E R; Quintão, E C R; Catanozi, S; Passarelli, M

2011-07-01

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of ¹⁴C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [³H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [³H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [³H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.

A comparison of the impact of amaranth flour and squalene on plasma cholesterol in mice with diet-induced dyslipidemia.

PubMed

Chmelík, Zdenek; Kotolová, Hana; Piekutowská, Zuzana; Horská, Katerina; Bartosová, Ladislava; Suchý, Pavel; Kollár, Peter

2013-01-01

Amaranth was identified as a possible component of an anti-sclerotic diet. To date, particular substances responsible for this effect have not been exactly specified. Squalene, which is contained in amaranth, could be responsible for this effect. However, there are also other potential substances and the hypolipidemic effect of amaranth can be caused by a synergistic effect of several components. This study investigated and compared the impact of amaranth flour and squalene on the total cholesterol (CHOL(TOT)) and LDL cholesterol (CHOL(LDL)) levels in mice with dyslipidemia induced by a cholesterol- and sugar-rich diet. The experiment included 40 inbred mice (C57Bl/6J SPF). After a 7-days acclimatization period, animals were divided into four groups by random. Individual groups were fed different diets for 49 days: control (group C), high energy diet (group HED), high energy diet with amaranth flour (group HED+A) and high energy diet with squalene (group HED+S). The sugar- and cholesterol-rich diet in HED resulted in the significant increase in the levels of CHOL(TOT) by 125% (P < 0.05) and CHOL(LDL) by 304% (P < 0.05), and at the same time in a decrease of HDL cholesterol (CHOL(HDL)) levels by 58% (P < 0.05) compared to group C. To the contrary, amaranth flour enriched diet in group HED+A led to a decrease of CHOL(TOT) levels by 33% (P < 0.05) and CHOL(LDL) by 37% (P < 0.05), compared to HED. Both, amaranth flour and squalene, had a positive impact on CHOL(HDL) levels. Compared to group HED, there was a 47% increase in HED+A and a 60% increase in HED+S. Results proved the favorable impact of amaranth flour on the levels of total cholesterol CHOL(TOT) and also on CHOL(LDL). Furthermore, the results imply that amaranth flour contains besides squalene other substances, which can actively participate in its hypolipidemic effect.

Cholesterol-lowering effects of dietary pomegranate extract and inulin in mice fed an obesogenic diet.

PubMed

Yang, Jieping; Zhang, Song; Henning, Susanne M; Lee, Rupo; Hsu, Mark; Grojean, Emma; Pisegna, Rita; Ly, Austin; Heber, David; Li, Zhaoping

2018-02-01

It has been demonstrated in animal studies that both polyphenol-rich pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic changes induced by a high-fat diet, but little is known about the specific mechanisms. This study evaluated the effect of PomX (0.25%) and inulin (9%) alone or in combination on cholesterol and lipid metabolism in mice. Male C57BL/6 J mice were fed high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose)] diets supplemented with PomX (0.25%) and inulin (9%) alone or in combination for 4 weeks. At the end of intervention, serum and hepatic cholesterol, triglyceride levels, hepatic gene expression of key regulators of cholesterol and lipid metabolism as well as fecal cholesterol and bile acid excretion were determined. Dietary supplementation of the HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol. Supplementation with PomX and inulin together resulted in lower hepatic and serum total cholesterol compared to individual treatments. Compared to HF/HS control, PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid synthesis pathways. Inulin decreased gene expression of key regulators of cholesterol de novo synthesis Srebf2 and Hmgcr and significantly increased fecal elimination of total bile acids and neutral sterols. Only PomX in combination with inulin reduced liver and lipid weight significantly compared to the HF/HS control group. PomX showed a trend to decrease liver triglyceride (TG) levels, while inulin or PomX-inulin combination had no effect on either serum or liver TG levels. Dietary PomX and inulin supplementation decreased hepatic and serum total cholesterol by different mechanisms and the combination leading to a significant enhancement of the cholesterol-lowering effect. Copyright © 2017 Elsevier Inc. All rights reserved.

[Polymorphism in the regulatory part of the cholesterol 7 alpha hydroxylase gene in children with high and low levels of cholesterol].

PubMed

Hubácek, J A; Pistulková, H; Skodová, Z; Lánská, V; Poledne, R

2003-01-01

High plasma cholesterol is one of the risk factors of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been concerned in the development of hypercholesterolemia. Cholesterol 7 alpha hydroxylase (CYP-7A1) is a key enzyme in the bile acid synthesis and it plays an important role in cholesterol catabolism. The aim of the study was to establish the role of A-204-->C polymorphism in CYP-7A1 gene in plasma lipid determination in children. Using PCR and restriction analysis (BsaI) we have measured A-204-->C polymorphism in CYP-7A1 gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high- (HCG) and eighty-six children in low- (LCG) cholesterolemic groups participated in the study. No significant difference was found in the frequencies of the genotypes or alleles of the A-204-->C polymorphism in the CYP-7A1 gene between HCG and LCG. In HCG, C/C-204 homozygotes have the highest and A/A homozygotes the lowest levels of LDL-cholesterol (4.21 +/- 0.68 mmol/l vers. 3.69 +/- 0.60 mmol/l, p < 0.05). No associations between lipid parameters and genotypes within the LCG group were found. The A-204-->C polymorphism in the gene for CYP-7A1 is not the major determinant of plasma lipid levels in childhood. Its impact is expressed only on high cholesterol background.

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

PubMed

Papazyan, Romeo; Liu, Xueqing; Liu, Jingwen; Dong, Bin; Plummer, Emily M; Lewis, Ronald D; Roth, Jonathan D; Young, Mark A

2018-06-01

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia.

PubMed

Stein, Evan A; Bays, Harold; O'Brien, Dennis; Pedicano, Jim; Piper, Edward; Spezzi, Andrea

2011-05-10

Lapaquistat acetate is a squalene synthase inhibitor investigated for the treatment of hypercholesterolemia. This report summarizes the phase 2 and 3 results from the lapaquistat clinical program, which was halted at an advanced stage as a result of potential hepatic safety issues. Efficacy and safety data were pooled from 12 studies (n=6151). These were 6- to 96-week randomized, double-blind, parallel, placebo- or active-controlled trials with lapaquistat monotherapy or coadministration with other lipid-altering drugs in dyslipidemic patients, including a large (n=2121) 96-week safety study. All studies included lapaquistat 100 mg daily; 5 included 50 mg; and 1 included 25 mg. The main outcome measures were the percent change in low-density lipoprotein cholesterol, secondary lipid/metabolic parameters, and overall safety. Lapaquistat 100 mg significantly decreased low-density lipoprotein cholesterol by 21.6% in monotherapy and by 18.0% in combination with a statin. It also reduced other cardiovascular risk markers, such as C-reactive protein. Total adverse events were higher for lapaquistat than placebo, although individual events were generally similar. At 100 mg, there was an increase in alanine aminotransferase value ≥3 times the upper limit of normal on ≥2 consecutive visits (2.0% versus 0.3% for placebo in the pooled efficacy studies; 2.7% versus 0.7% for low-dose atorvastatin in the long-term study). Two patients receiving lapaquistat 100 mg met the Hy Law criteria of alanine aminotransferase elevation plus increased total bilirubin. Squalene synthase inhibition with lapaquistat acetate, alone or in combination with statins, effectively lowered low-density lipoprotein cholesterol in a dose-dependent manner. Elevations in alanine aminotransferase, combined with a rare increase in bilirubin, presented potential hepatic safety issues, resulting in termination of development. The lapaquistat experience illustrates the current challenges in lipid-altering drug development. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00487994, NCT00143663, NCT00143676, NCT00864643, NCT00263081, NCT00286481, NCT00249899, NCT00249912, NCT00813527, NCT00256178, NCT00268697, and NCT00251680.

Chromium picolinate inhibits cholesterol-induced stimulation of platelet aggregation in hypercholesterolemic rats.

PubMed

Seif, A A

2015-06-01

Hypercholesterolemia indirectly increases the risk of myocardial infarction by enhancing platelet aggregation. Chromium has been shown to lower plasma lipids. This study was designed to investigate whether chromium inhibits platelet aggregation under hypercholesterolemic conditions. Albino rats were divided into four groups: control rats fed with a normolipemic diet (NLD group), chromium-supplemented rats fed with NLD (NLD + Cr group), rats fed with a high-fat diet (HF group), and chromium-supplemented rats fed with HF (HF + Cr group). After 10 weeks, blood was collected to determine adenosine diphosphate and collagen-induced platelet aggregation and plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, and thromboxane B2. Low-density lipoprotein cholesterol was calculated by Friedewald formula. High-fat diet animals displayed significant elevation of plasma lipids and platelet aggregation which was normalized to control levels by chromium supplementation. Chromium supplementation in normolipemic (NLD + Cr) rats did not produce significant changes in either plasma lipids or platelet activity. Chromium supplementation to hypercholesterolemic rats improves the lipid profile and returns platelet hyperaggregability to control levels. This normalization is mostly due to a reduction in plasma cholesterol level.

Trans fatty acids and cholesterol levels: an evidence map of the available science

USDA-ARS?s Scientific Manuscript database

High intakes of industrial trans fatty acids (iTFA) increase circulating low density lipoprotein cholesterol (LDL-C) levels, which has implicated iTFA in coronary heart disease (CHD) risk. Published data on iTFA and LDL-C, however, represent higher intake levels than the U.S. population currently co...

Targeted Lipidomic Analysis of Oxysterols in the Embryonic Central Nervous System

PubMed Central

Wang, Yuqin; Sousa, Kyle M.; Bodin, Karl; Theofilopoulos, Spyridon; Sacchetti, Paola; Hornshaw, Martin; Woffendin, Gary; Karu, Kersti; Sjövall, Jan; Arenas, Ernest; Griffiths, William J.

2009-01-01

Summary In this study two regions of embryonic (E11) mouse central nervous system (CNS) have been profiled for their unesterified sterol content. Using high-performance liquid chromatography (HPLC) – mass spectrometry (MS) and tandem mass spectrometry (MSn) low levels of oxysterols (estimated 2 – 165 ng/g wet weight) were identified in cortex (Ctx) and spinal cord (Sc). The identified oxysterols include 7α-, 7β-, 22R-, 24S-, 25- and 27-hydroxycholesterol; 24,25- and 24,27-dihydroxycholesterol; and 24S,25-epoxycholesterol. Of these, 24S-hydroxycholesterol is biosynthesised exclusively in brain. In comparison to adult mouse where the 24S-hydroxycholesterol level is about 40 μg/g in brain the level of 24S-hydroxycholesterol reported here (estimated 26 ng/g in Ctx and 13 ng/g in Sc) is extremely low. Interestingly, the level of 24S,25-epoxycholesterol in both CNS regions (estimated 165 ng/g in Ctx and 91 ng/g in Sc) is somewhat higher than the levels of the hydroxycholesterols. This oxysterol is formed in parallel to cholesterol via a shunt of the mevalonate pathway and its comparatively high abundance may be a reflection of a high rate of cholesterol synthesis at this stage of development. Levels of cholesterol (estimated 1.25 mg/g in Ctx and 1.15 mg/g in Sc) and its precursors were determined by gas chromatography – mass spectrometry (GC-MS). In both CNS regions cholesterol levels were found to be lower than those reported in the adult, but in relation to cholesterol the levels of cholesterol precursors were higher than found in adult indicating a high rate of cholesterol synthesis. In summary, our data provide evidence for the presence of endogenous oxysterols in two brain regions of the developing CNS. Moreover, while most of the enzymes involved in hydroxysterol synthesis are minimally active at E11, our results suggest that the mevalonate pathway is significantly active, opening up the possibility for a function of 24S,25-epoxycholesterol during brain development. PMID:19381367

78 FR 48516 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... Rotations, Halts and Suspensions'' and Rule 1047A, entitled ``Trading Rotations, Halts or Reopenings'' to... trading for technical issues on Phlx. \\3\\ See Rule 1. An ``Option Exchange Official'' is an Exchange staff...

Effect of adiponectin-encoding gene ADIPOQ single nucleotide polymorphisms +45 and +276 on serum lipid levels after antiretroviral therapy in Japanese patients with HIV-1-infection.

PubMed

Kato, Hideaki; Ohata, Aya; Samukawa, Sei; Ueda, Atsuhisa; Ishigatsubo, Yoshiaki

2016-04-01

To investigate the association between single nucleotide polymorphisms (SNPs) in the adiponectin-encoding gene ADIPOQ and changes in serum lipid levels in HIV-1-infected patients after antiretroviral therapy (ART). ART-naïve HIV-1-infected patients were recruited to this prospective analysis. SNP +45 and SNP +276 genotype was determined by direct sequencing. Multivariate linear regression analysis was performed to analyse the effects of genotype, and predisposing conditions on serum total cholesterol and triglyceride in the 4 months before and after ART initiation. The study enrolled 78 patients with HIV-1-infection (73 male, five female; age range 22-67 years). HIV-1 viral load ≥5 log10 copies/ml, baseline total cholesterol ≥160 mg/dl, and CD4(+) lymphocyte count <200/µl were associated with increased serum total cholesterol levels after ART initiation. Protease inhibitor treatment and body mass index ≥25 kg/m(2) were associated with increased triglyceride levels after ART initiation. There were no significant associations between SNP +45 or SNP +276 genotype and serum total cholesterol or triglyceride levels. SNP +45 and SNP +276 genotype is not associated with changes in serum total cholesterol or triglyceride levels after ART initiation. © The Author(s) 2016.

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

PubMed

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.

Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Di-xian, E-mail: luodixian_2@163.com; Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan; First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan

Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different staticmore » pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. Conclusion: Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1.« less

Commonwealth Power in Respect of Vocational Education in Australia: Some Historical Vignettes with Future Potential

ERIC Educational Resources Information Center

Ryan, Robin J.

2007-01-01

Intervention in vocational education and training by the federal level of government in Australia (the Commonwealth) expanded exponentially in the last quarter of the 20th century, after halting and intermittent involvement in earlier decades. Such intervention in a field of public policy once considered the exclusive preserve of the States…

Population-Level Effect of Cholera Vaccine on Displaced Populations, South Sudan, 2014.

PubMed

Azman, Andrew S; Rumunu, John; Abubakar, Abdinasir; West, Haley; Ciglenecki, Iza; Helderman, Trina; Wamala, Joseph Francis; Vázquez, Olimpia de la Rosa; Perea, William; Sack, David A; Legros, Dominique; Martin, Stephen; Lessler, Justin; Luquero, Francisco J

2016-06-01

Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.

Halting Dropouts: To Be or Not To Be, There Can Be No Question!

ERIC Educational Resources Information Center

Henry, Mildred Dalton

This article explores the dropout problem at national, regional, and local levels. The demographics of dropouts are examined with particular emphasis on cultural variables and the plight of minorities. The need for community-based education is explored, and a model that has proved successful is outlined for dropout prevention, intervention, and…

Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

PubMed

Wu, T; Trevisan, M; Genco, R J; Falkner, K L; Dorn, J P; Sempos, C T

2000-02-01

Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and meta-analysis.

PubMed

Schwingshackl, Lukas; Hoffmann, Georg

2013-12-01

Dietary fat plays an important role in the primary prevention of cardiovascular disease, but long-term (≥12 months) effects of different percentages of fat in the diet on blood lipid levels remain to be established. Our systematic review and meta-analysis focused on randomized controlled trials assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels. Relevant randomized controlled trials were identified searching MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two studies were included in the meta-analysis. Decreases in total cholesterol (weighted mean difference -4.55 mg/dL [-0.12 mmol/L], 95% CI -8.03 to -1.07; P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference -3.11 mg/dL [-0.08 mmol/L], 95% CI -4.51 to -1.71; P<0.0001) were significantly more pronounced following low-fat diets, whereas rise in high-density lipoprotein (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29 to 3.42; P<0.0001) and reduction in triglyceride levels (weighted mean difference -8.38 mg/dL [-0.095 mmol/L], 95% CI -13.50 to -3.25; P=0.001) were more distinct in the high-fat diet groups. Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. Meta-regression revealed that lower total cholesterol level was associated with lower intakes of saturated fat and higher intakes of polyunsaturated fat, and increases in HDL cholesterol levels were related to higher amounts of total fat largely derived from monounsaturated fat (of either plant or animal origin) in high-fat diets (composition of which was ~17% of total energy content in the form of monounsaturated fatty acids, ~8% of total energy content in the form of polyunsaturated fatty acids), whereas increases in triglyceride levels were associated with higher intakes of carbohydrates. In addition, lower LDL cholesterol level was marginally associated with lower saturated fat intake. The results of our meta-analysis do not allow for an unequivocal recommendation of either low-fat or high-fat diets in the primary prevention of cardiovascular disease. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study

PubMed Central

Spigoni, Valentina; Antonini, Monica; Micheli, Maria Maddalena; Fantuzzi, Federica; Fratter, Andrea; Pellizzato, Marzia; Derlindati, Eleonora; Zavaroni, Ivana; Bonadonna, Riccardo C.; Dei Cas, Alessandra

2017-01-01

Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels are independent risk factors for cardiovascular (CV) mortality with no documented threshold. A new combination of nutraceuticals (berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid-lowering properties has become available. The aim of the study is to test the efficacy of the nutraceutical formulation (one daily) in lowering non-HDL cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. 39 subjects (age 52 ± 11 years; 54% females; body mass index 27 ± 4 kg/m2) were randomized (3:1) in a double blind phase II placebo-controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC) number were assessed. Baseline characteristics were comparable in the two groups. The intervention significantly decreased non-HDL cholesterol (−30 ± 20 mg/dL; p = 0.012), LDL cholesterol (−31 ± 18 mg/dL, p = 0.011) and apolipoprotein (Apo) B (−14 ± 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory, hormonal, PCSK9 and EPC levels remained stable throughout the study in both groups. The intervention was well tolerated. Three adverse events occurred: Epstein Barr virus infection, duodenitis and asymptomatic but significant increase in creatine phosphokinase (following intense physical exercise) which required hospitalization. The tested nutraceutical formulation may represent a possible therapeutic strategy in dyslipidemic individuals in primary prevention. PMID:28704936

Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study

PubMed Central

2013-01-01

Background Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. Methods Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. Results The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05). Conclusions Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. Trial registration Current Controlled Trials ISRCTN89549017 PMID:23297818

Effects of climatic factors on plasma lipid levels: A 5-year longitudinal study in a large Chinese population.

PubMed

Zhou, Xiaoming; Lin, Haiyan; Zhang, Shigang; Ren, Jianwei; Wang, Zhe; Zhang, Yun; Wang, Mansen; Zhang, Qunye

2016-01-01

The rules and mechanisms of seasonal changes in plasma lipid levels, which may be related to annual rhythmicity of incidence and mortality of cardiovascular diseases, are still controversial. The objectives of this study were to study the effects of climatic factors on plasma lipid levels and to preliminarily reveal mechanisms of annual rhythmicity of plasma lipid levels. A longitudinal study was performed using health examination data of 5 consecutive years (47,270 subjects) in Jinan, China. The climate in Jinan is typical temperate continental monsoon climate with huge temperature difference between winter and summer (>30°C). After considering and adjusting those classical lipid-associated risk factors, such as age, gender, diet, exercise, blood pressure, body weight, change of body weight, body mass index, glycemia, alanine aminotransferase, and creatinine, only air temperature could still significantly affect plasma lipid levels among the main climatic factors (humidity, precipitation, and so forth). For men, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was decreased significantly 0.35, 0.18, and 0.06 mmol/L, respectively, whereas triglyceride was increased significantly 0.12 mmol/L for every 10°C increase in air temperature. For women, total cholesterol and high-density lipoprotein cholesterol were decreased notably 0.73 and 0.32 mmol/L, and low-density lipoprotein cholesterol was increased significantly 0.26 mmol/L for every 10°C increase in air temperature, whereas triglyceride was not significantly affected by air temperature. Air temperature is an independent risk factor for plasma lipid levels besides those classical lipid-associated risk factors. The annual air temperature fluctuations might be an important mechanism of the seasonal changes of lipids. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study.

PubMed

Spigoni, Valentina; Aldigeri, Raffaella; Antonini, Monica; Micheli, Maria Maddalena; Fantuzzi, Federica; Fratter, Andrea; Pellizzato, Marzia; Derlindati, Eleonora; Zavaroni, Ivana; Bonadonna, Riccardo C; Dei Cas, Alessandra

2017-07-12

Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels are independent risk factors for cardiovascular (CV) mortality with no documented threshold. A new combination of nutraceuticals (berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid-lowering properties has become available. The aim of the study is to test the efficacy of the nutraceutical formulation (one daily) in lowering non-HDL cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. 39 subjects (age 52 ± 11 years; 54% females; body mass index 27 ± 4 kg/m²) were randomized (3:1) in a double blind phase II placebo-controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC) number were assessed. Baseline characteristics were comparable in the two groups. The intervention significantly decreased non-HDL cholesterol (-30 ± 20 mg/dL; p = 0.012), LDL cholesterol (-31 ± 18 mg/dL, p = 0.011) and apolipoprotein (Apo) B (-14 ± 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory, hormonal, PCSK9 and EPC levels remained stable throughout the study in both groups. The intervention was well tolerated. Three adverse events occurred: Epstein Barr virus infection, duodenitis and asymptomatic but significant increase in creatine phosphokinase (following intense physical exercise) which required hospitalization. The tested nutraceutical formulation may represent a possible therapeutic strategy in dyslipidemic individuals in primary prevention.

Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet

PubMed Central

2011-01-01

Background Inflammation process plays an important role in the development of atherosclerosis. Hypercholesterolemia is one of the major risk factors for atherosclerosis. The present study aimed to evaluate the effect of aqueous extract of Piper sarmentosum (P.s) on inflammatory markers like vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and C-reactive protein (CRP). Methods Forty two male New Zealand white rabbits were divided equally into seven groups; (i) C- control group fed normal rabbit chow (ii) CH- cholesterol diet (1%cholesterol) (iii) X1- 1% cholesterol with water extract of P.s (62.5 mg/kg) (iv) X2- 1% cholesterol with water extract of P.s (125 mg/kg (v) X3- 1% cholesterol with water extract of P.s (250 mg/kg) (vi) X4- 1% cholesterol with water extract of P.s (500 mg/kg) and (vii) SMV group fed with 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. Blood serum was taken for observing the inflammatory markers at the beginning and end of the experiment. Results Rabbits fed with 1% cholesterol diet (CH) showed significant increase in the level of VCAM-1, ICAM-1 and CRP compared to the C group. The levels of VCAM-1, ICAM-1 and CRP in the 1% cholesterol group and supplemented with P.s (500 mg/kg) were significantly reduced compared to the cholesterol group. Similar results were also reported with simvistatin group. Conclusion These results suggest that the supplementation of Piper sarmentosum extract could inhibit inflammatory markers which in turn could prevent atherosclerosis. PMID:21214952

Effects of dietary cholesterol on antioxidant capacity, non-specific immune response, and resistance to Aeromonas hydrophila in rainbow trout (Oncorhynchus mykiss) fed soybean meal-based diets.

PubMed

Deng, Junming; Kang, Bin; Tao, Linli; Rong, Hua; Zhang, Xi

2013-01-01

This study evaluated the effects of dietary cholesterol on antioxidant capacity, non-specific immune response and resistance to Aeromonas hydrophila in rainbow trout (Oncorhynchus mykiss) fed soybean meal-based diets. Fish were fed diets supplemented with graded cholesterol levels (0 [control], 0.3, 0.6, 0.9, 1.2, and 1.5%) for nine weeks. The fish were then challenged by A. hydrophila and their survival rate recorded for the next week. Dietary cholesterol supplementation generally increased the serum and hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (TAC) activities, but decreased the serum and hepatic malondialdehyde (MDA) contents. Further, the hepatic CAT and serum SOD, CAT, and TAC activities were significantly higher in fish fed diets supplemented with 0.9 or 1.2% cholesterol compared to those fed the control diet, whereas the serum and hepatic MDA contents were significantly lower. The respiratory burst activity, alternative complement activity, and hepatic lysozyme activity increased steadily when the supplemental cholesterol was increased by up to 1.2% and then declined with further addition. The serum lysozyme activity and phagocytic activity increased steadily with increasing dietary supplemental cholesterol level up to 0.9% and then declined with further addition. Dietary cholesterol supplementation generally enhanced the protection against A. hydrophila infection, and fish fed diets supplemented with 0.9 or 1.2% cholesterol exhibited the highest post-challenge survival rate. The results indicated that cholesterol may be under-supplied in rainbow trout fed soybean meal-based diets, and dietary cholesterol supplementation (0.9-1.2%) contributed to improved immune response and disease resistance of rainbow trout against A. hydrophila. Published by Elsevier Ltd.

A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.

PubMed

Werner, Hauke B; Krämer-Albers, Eva-Maria; Strenzke, Nicola; Saher, Gesine; Tenzer, Stefan; Ohno-Iwashita, Yoshiko; De Monasterio-Schrader, Patricia; Möbius, Wiebke; Moser, Tobias; Griffiths, Ian R; Nave, Klaus-Armin

2013-04-01

The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2015-03-01

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.

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

PubMed

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. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

PubMed Central

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

2008-01-01

Background Coronary heart disease is increasing in urban Indian subjects and lipid abnormalities are important risk factors. To determine secular trends in prevalence of various lipid abnormalities we performed studies in an urban Indian population. Methods Successive epidemiological Jaipur Heart Watch (JHW) studies were performed in Western India in urban locations. The studies evaluated adults ≥ 20 years for multiple coronary risk factors using standardized methodology (JHW-1, 1993–94, n = 2212; JHW-2, 1999–2001, n = 1123; JHW-3, 2002–03, n = 458, and JHW-4 2004–2005, n = 1127). For the present analyses data of subjects 20–59 years (n = 4136, men 2341, women 1795) have been included. In successive studies, fasting measurements for cholesterol lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol) and triglycerides were performed in 193, 454, 179 and 252 men (n = 1078) and 83, 472, 195, 248 women (n = 998) respectively (total 2076). Age-group specific levels of various cholesterol lipoproteins, triglycerides and their ratios were determined. Prevalence of various dyslipidemias (total cholesterol ≥ 200 mg/dl, LDL cholesterol ≥ 130 mg/dl, non-HDL cholesterol ≥ 160 mg/dl, triglycerides ≥ 150 mg/dl, low HDL cholesterol <40 mg/dl, high cholesterol remnants ≥ 25 mg/dl, and high total:HDL cholesterol ratio ≥ 5.0, and ≥ 4.0 were also determined. Significance of secular trends in prevalence of dyslipidemias was determined using linear-curve estimation regression. Association of changing trends in prevalence of dyslipidemias with trends in educational status, obesity and truncal obesity (high waist:hip ratio) were determined using two-line regression analysis. Results Mean levels of various lipoproteins increased sharply from JHW-1 to JHW-2 and then gradually in JHW-3 and JHW-4. Age-adjusted mean values (mg/dl) in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed a significant increase in total cholesterol (174.9 ± 45, 196.0 ± 42, 187.5 ± 38, 193.5 ± 39, 2-stage least-squares regression R = 0.11, p < 0.001), LDL cholesterol (106.2 ± 40, 127.6 ± 39, 122.6 ± 44, 119.2 ± 31, R = 0.11, p < 0.001), non-HDL cholesterol (131.3 ± 43, 156.4 ± 43, 150.1 ± 41, 150.9 ± 32, R = 0.12, p < 0.001), remnant 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 < 0.001) and 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 ≥ 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol < 40 mg/dl (46.2, 53.3, 55.4, 33.7, R = 0.136). Increase was observed in prevalence of high non-HDL 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 ≥ 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and ≥ 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 < 0.05). Greater educational level, as marker of socioeconomic status, correlated significantly with increasing obesity (r2 men 0.98, women 0.99), and truncal obesity (r2 men 0.71, women 0.90). Conclusion In an urban Indian population, trends reveal increase in mean total-, non-HDL-, remnant-, and total:HDL 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. PMID:18950504

Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation

PubMed Central

Mumford, Sunni L.; Schisterman, Enrique F.; Siega-Riz, Anna Maria; Gaskins, Audrey J.; Steiner, Anne Z.; Daniels, Julie L.; Olshan, Andrew F.; Hediger, Mary L.; Hovey, Kathleen; Wactawski-Wende, Jean; Trevisan, Maurizio; Bloom, Michael S.

2011-01-01

BACKGROUND Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation. METHODS The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18–44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles. RESULTS Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005). CONCLUSIONS These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome. PMID:21115506

Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis.

PubMed

Shen, Li; Peng, Hongchun; Peng, Ran; Fan, Qingsong; Zhao, Shuiping; Xu, Danyan; Morisseau, Christophe; Chiamvimonvat, Nipavan; Hammock, Bruce D

2015-04-01

Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease. The sEH is highly expressed in adipocytes, and it converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids. We previously showed that increasing EETs levels with a sEH inhibitor (sEHI) (t-AUCB) resulted in elevated ABCA1 expression and promoted ABCA1-mediated cholesterol efflux from 3T3-L1 adipocytes. The present study investigates the impacts of t-AUCB in mice deficient for the low density lipoprotein (LDL) receptor (Ldlr(-/-) mice) with established atherosclerotic plaques. The sEH inhibitor delivered in vivo for 4 weeks decreased the activity of sEH in adipose tissue, enhanced ABCA1 expression and cholesterol efflux from adipose depots, and consequently increased HDL levels. Furthermore, t-AUCB enhanced RCT to the plasma, liver, bile and feces. It also showed the reduction of plasma LDL-C levels. Consistently, t-AUCB-treated mice showed reductions in the size of atherosclerotic plaques. These studies establish that raising adipose ABCA1 expression, cholesterol efflux, and plasma HDL levels with t-AUCB treatment promotes RCT, decreasing LDL-C and atherosclerosis regression, suggesting that sEH inhibition may be a promising strategy to treat atherosclerotic vascular disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hypolipidemic, antioxidant and antiatherogenic property of sardine by-products proteins in high-fat diet induced obese rats.

PubMed

Affane, Fouad; Louala, Sabrine; El Imane Harrat, Nour; Bensalah, Fatima; Chekkal, Hadjera; Allaoui, Amine; Lamri-Senhadji, Myriem

2018-04-15

Fish by-products valorization on account of their richness in bioactive compounds may represent a better alternative to marine products with a view to economic profitability and sustainable development. In this study, we compared the effect of sardine by-product proteins (SBy-P), with those of the fillets (SF-P) or casein (Cas), on growth parameters, serum leptin level, lipids disorders, lipid peroxidation and reverse cholesterol transport, in diet-induced obese rats. Obesity was induced by feeding rats a high-fat diet (20% sheep fat), during 12 weeks. At body weight (BW) of 400 ± 20 g, eighteen obese rats were divided into three homogenous groups and continue to consume the high-fat diet for 4 weeks containing either, 20% SBy-P, SF-P or Cas. The results showed that SBy-P, compared to SF-P and Cas, efficiently reduced food intake (FI), BW gain and serum leptin level, and improved blood lipids levels and reverse cholesterol transport by reducing total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-HDL 1 -C) serum levels, increasing the level of high-density lipoprotein cholesterol (HDL 2 -C and HDL 3 -C), and enhancing lecithin: cholesterol acyltransferase (LCAT) activity. Furthermore, they attenuated lipid peroxidation by increasing atheroprotective activity of the paraoxonase-1 (PON-1). Sardine by-product proteins due to their richness in certain essential amino acids, highlight weight-loss, lipid-lowering, antioxidant and anti-atherogenic potentials, contributing to the improvement of the complications associated with obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

PubMed Central

Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

2015-01-01

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia. PMID:26694461

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.

PubMed

Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

2015-12-17

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

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

PubMed

Beena, A; Prasad, V

1997-08-01

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

Barley β-glucan reduces blood cholesterol levels via interrupting bile acid metabolism.

PubMed

Wang, Yanan; Harding, Scott V; Thandapilly, Sijo J; Tosh, Susan M; Jones, Peter J H; Ames, Nancy P

2017-11-01

Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosity β-glucan consumption in those individuals.

Effect of clot aging and cholesterol content on ultrasound-assisted thrombolysis.

PubMed

Zhou, Yufeng; Murugappan, Suresh Kanna; Sharma, Vijay Kumar

2014-10-01

Exposure to 2-MHz transcranial diagnostic ultrasound enhances the thrombolytic activity of intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (sonothrombolysis). However, rates of arterial recanalization vary widely, depending upon the clot burden, its location, and stroke subtype. We evaluated the influence of age and cholesterol level of the blood clots on sonothrombolysis in an in vitro model. To "age" the clots, serum was replaced by fresh blood periodically. We increased the cholesterol content of the clots by adding cholesterin to the blood. The clots were lysed by tPA and/or transcranial Doppler ultrasound sonication for 1 h. The extent of thrombolysis induced by various treatment protocols (controls, sonication, tPA, and sonothrombolysis) was evaluated with relative changes in the clot weights and in the clot structure by scanning electron microscopy (SEM) at end of the experiment. Sonothrombolysis induced significantly higher weight reduction in fresh clots (37.3 % in 2-h old clots versus 24.8 % in 10-h ones, p < 0.005) as well as the clots with higher cholesterol levels (41.7 versus 30.6 % in normal cholesterol clots, p < 0.005). SEM demonstrated patterns of clot dissolution among various treatment modalities. Sonothrombolysis induced better clot lysis in fresh thrombi with high cholesterol levels.

[Potential role of cholesterol in distinguishing malignant from benign pleural effusion].

PubMed

Plavec, Goran; Tomić, Ilija; Nidzović, Natasa; Radojcić, Branko; Aćimović, Slobodan; Bokun, Radojka

2004-01-01

Cholesterol and carcinoembryonic antigen (CEA) levels in pleural effusion and sera, were measured in 199 patients with pleural effusions of various origins. Malignant cause was found in 93, and nonmalignant in 106 patients. Mean cholesterol level in sera of patient with malignant disease was 5.0 +/- 0.93 mmol/L, and in nonmalignant group 4.34 +/- 1.32 mmol/L. The difference was not statistically significant. Mean cholesterol level in nonmalignant pleural effusions was higher thAn those in malignant (2.51 +/- 1.23 mmol/L; and 2.28 +/- 1.06 mmol/L), but the difference was also not significant. Average pleural fluid/serum cholesterol ratio (Holl/S) in nonmalignant group was 0.61 +/- 0.32 and in malignant group 0.46 +/- 0.22. The difference between those mean values was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106 and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%, positive predictive value 76%, negative predictive value 65% and accuracy 69%. Significant negative correlation between Holi/S and pleural fluid CEA was found (p < 0.05). It was assumed that pleural fluid/serum cholesterol ratio lower than 0.5 could be of great benefit, as an additional test in the differentiation of malignant from benign pleural effusion.

Effects of different fibre sources and fat addition on cholesterol and cholesterol-related lipids in blood serum, bile and body tissues of growing pigs.

PubMed

Kreuzer, M; Hanneken, H; Wittmann, M; Gerdemann, M M; Machmuller, A

2002-04-01

Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that the use of citrus pulp increased serum cholesterol concentrations when levels were low in the corresponding low-BFS diets (low-fat and soy bean diets), but caused no further increase in the coconut-oil/palm kernel oil blend diet. From the present results it seems that fermentable hemicelluloses have a more favourable effect of decreasing metabolic cholesterol and related traits than hardly digestible fibre, fermentable cellulose or, particularly, pectin. Furthermore, some types of fibre expressed a certain potential to reduce cholesterol content of fat pork and pork products by up to 10% (experiment 1) and 25% (experiment 2).

Identification of the active protein in rice bran protein having an inhibitory activity of cholesterol micellar solubility.

PubMed

Wang, Jilite; Shimada, Masaya; Nagaoka, Satoshi

2017-06-01

In our previous study, rice bran protein (RBP) inhibited cholesterol micellar solubility in vitro and decreased serum cholesterol level in rats. In the present study, RBP was separated and purified by size-exclusion chromatography and reversed-phase chromatography. The active protein of RBP related to cholesterol micellar solubility was identified as lectin and non-specific lipid-transfer protein 1 using MALDI-TOF mass spectrometry analysis.

Operation Everest II. Plasma Lipid and Hormonal Responses

DTIC Science & Technology

1988-01-01

cholesterol [TC] and high density lipoprotein cholesterol [ HDL -C] concentrations are shown in Fig 2. Pre-ascent...of altitude on fasting total cholesterol and high density lipoprotein ( HDL ) cholesterol concentrations. ** = p<O.Ol from 760 Torr Figure 3: The effect...157.7*9.7 mg/dl, decreased by 25% to .6 118.3*13.5 mg/dl following the 40-day exposure (p<O.Ol). High density lipoprotein [ HDL -C] levels

Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus

PubMed Central

Freeman, Linnea R.; Haley-Zitlin, Vivian; Stevens, Cheryl; Granholm, Ann-Charlotte

2014-01-01

Consumption of a high-fat and/or high-cholesterol diet can have detrimental effects on the brain. In the present study, dietary treatment with saturated fats, trans fats, or cholesterol to middle-aged Fischer 344 rats resulted in alterations to serum triglyceride and cholesterol levels, organ weights, and hippocampal morphology. Previously, we demonstrated that a 10% hydrogenated coconut oil and 2% cholesterol diet resulted in worse performance on the 12-day water radial arm maze, increased cholesterol and triglyceride levels, and decreased dendritic microtubule associated protein 2 (MAP2) staining in the hippocampus. The diets administered herein were used to examine components from the previous diet and further examine their effects on hippocampal morphology. Specifically, neuronal morphology, dendritic integrity, fatty acid metabolism, microgliosis, and blood vessel structure in the hippocampus and/or adjacent structures were explored. Our results indicate alterations to peripheral and neural systems following each of the diets. PMID:21535919

Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders

PubMed Central

Akerblom, Jennifer L.; Costa, Rosann; Luchsinger, Jose A.; Manly, Jennifer J.; Tang, Ming-Xin; Lee, Joseph H; Mayeux, Richard; Schupf, Nicole

2009-01-01

Objectives to investigate the relation of plasma lipids to all-cause mortality in a multi-ethnic cohort of non-demented elderly. Setting community-based sample of Medicare recipients, 65 years and older, residing in Northern Manhattan. Participants about two thousand five hundred and fifty-six non-demented elderly, 65–103 years. Among participants, 66.1% were women, 27.6% were White/non-Hispanic, 31.2% were African-American and 41.2% were Hispanic. Methods a standardised assessment, including functional ability, medical history, physical and neurological examination and a neuropsychological battery was conducted. Vital status was ascertained through the National Death Index (NDI). We used survival analyses stratified by race and ethnicity to examine the relation of plasma lipids to subsequent all-cause mortality. Results hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile (White HR: 2.2, for lowest total cholesterol quartile; HR: 2.3, for lowest non-HDL cholesterol quartile; and HR: 1.8, for lowest LDL cholesterol quartile. African-American HR: 1.9, for lowest total cholesterol, HR: 2.0, for lowest non-HDL cholesterol and HR: 1.9, for lowest LDL cholesterol). In contrast, plasma lipid levels were not related to mortality risk among Hispanics. Conclusions hispanic ethnicity modifies the associations between lipid levels and all-cause mortality in the elderly. PMID:18349015

Android and gynoid fat percentages and serum lipid levels in United States adults.

PubMed

Min, Kyoung-Bok; Min, Jin-Young

2015-03-01

Accumulating evidence suggests that fat distribution is a better predictor of cardiovascular disease than body mass index (BMI). The aim of this study was to investigate the association of android and gynoid fat percentages with lipid profiles to determine whether android and/or gynoid fat percentages are associated with serum lipid levels. A population-based cross-sectional study. Five thousand six hundred and ninety-six adults (20 years and older) who participated in the National Health and Nutrition Examination Survey 2003-2006. The regional body composition in the android and gynoid regions was defined by dual energy X-ray absorptiometry (DXA). The estimation of lipid risk profiles included total cholesterol, high-density lipoprotein (HDL) -cholesterol, low-density lipoprotein (LDL) -cholesterol and triglycerides (TG). Regardless of gender, android and gynoid body fat percentages were positively and significantly correlated with BMI and waist circumference. After adjustment for age, ethnicity, education, smoking, alcohol consumption, dyslipidaemia and BMI, increases in android fat percentage were significantly associated with total cholesterol, TG and HDL cholesterol in males, and total cholesterol, HDL cholesterol and LDL cholesterol in females. The gynoid fat percentages showed a positive correlation with total cholesterol in males, whereas gynoid fat accumulation in females showed a favourable association with TG and HDL cholesterol. The observed associations differed according to ethnic groups. Our results suggest that regional fat distribution in the android and gynoid regions have different effects on lipid profiles, and that fat in the android region, rather than the gynoid region, may be an important factor in determining the risk of cardiovascular disease. © 2014 John Wiley & Sons Ltd.

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis.

PubMed

Feillet, C; Cristol, J P; Michel, F; Kanouni, T; Navarro, R; Navarro, M; Monnier, L; Descomps, B

1997-01-01

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

PubMed

Dean, Bonnie B; Borenstein, Jeff E; Henning, James M; Knight, Kevin; Merz, C Noel Bairey

2004-06-01

The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction. A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated. Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction (P =.08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity (P =.20). Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.

Moderate consumption of beer reduces liver triglycerides and aortic cholesterol deposit in LDLr-/- apoB100/100 mice.

PubMed

Degrace, Pascal; Moindrot, Bastien; Mohamed, Ismaël; Gresti, Joseph; Clouet, Pierre

2006-12-01

This study was designed to address the effects of a moderate consumption of beer on serum and liver lipid parameters and on the development of aortic lesions in a mouse model associated with a human atherogenic lipoprotein profile. LDLr(-/-) apoB(100/100) mice received each day during 12 weeks either water, mild beer (0.570g of ethanol/kg of body weight) or ethanol-free beer in a single pure dose. Serum and liver lipid parameters were analyzed and atherosclerotic lesions were estimated in heart and aorta through their total cholesterol content. mRNA levels of enzymes and receptors involved in lipoprotein uptake, in fatty acid esterification and oxidation, and in reverse cholesterol transport were also measured in the liver. Serum glucose, triglyceride (TG) and cholesterol levels were altered neither by ethanol-free beer nor by mild beer. Nevertheless, both beer treatments significantly increased HDL-cholesterol (HDL-C) and VLDL-C levels by reference to controls with no change in LDL-C levels. Liver TG contents were significantly decreased by either beer treatment. Cholesterol accumulation was attenuated in the whole aorta of mice treated with mild beer at p<0.05 and not significantly with ethanol-free beer. Heart cholesterol contents were comparable in the three series. Among the genes studied, only scavenger receptor-B1 was downregulated by both beer-based beverages. LDL receptor related protein, lecithin-cholesterol acyltransferase and sterol regulatory element-binding protein 2 were downregulated only by mild beer. The expression of other genes assayed was not altered. When administered in chronic and moderate dose, unidentified components of beer may exert beneficial effects towards atherosclerosis development through alteration of lipoprotein metabolism in LDLr(-/-) apoB(100/100) mice. This effect was slightly amplified by the presence of ethanol in beer.

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study.

PubMed

Borgquist, Signe; Giobbie-Hurder, Anita; Ahern, Thomas P; Garber, Judy E; Colleoni, Marco; Láng, István; Debled, Marc; Ejlertsen, Bent; von Moos, Roger; Smith, Ian; Coates, Alan S; Goldhirsch, Aron; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Regan, Meredith M; Thürlimann, Beat

2017-04-10

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer-free interval, and distant recurrence-free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM‐INSULIN randomized trial

PubMed Central

Cariou, Bertrand; Müller‐Wieland, Dirk; Colhoun, Helen M.; Del Prato, Stefano; Tinahones, Francisco J.; Ray, Kausik K.; Bujas‐Bobanovic, Maja; Domenger, Catherine; Mandel, Jonas; Samuel, Rita; Henry, Robert R.

2017-01-01

Aims To investigate the efficacy and safety of alirocumab in participants with type 2 (T2D) or type 1 diabetes (T1D) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy. Methods Participants at high cardiovascular risk with T2D (n = 441) or T1D (n = 76) and LDL cholesterol levels ≥1.8 mmol/L (≥70 mg/dL) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks, for 24 weeks' double‐blind treatment. Alirocumab‐treated participants received 75 mg every 2 weeks, with blinded dose increase to 150 mg every 2 weeks at week 12 if week 8 LDL cholesterol levels were ≥1.8 mmol/L. Primary endpoints were percentage change in calculated LDL cholesterol from baseline to week 24, and safety assessments. Results Alirocumab reduced LDL cholesterol from baseline to week 24 by a mean ± standard error of 49.0% ± 2.7% and 47.8% ± 6.5% vs placebo (both P < .0001) in participants with T2D and T1D, respectively. Significant reductions were observed in non‐HDL cholesterol (P < .0001), apolipoprotein B (P < .0001) and lipoprotein (a) (P ≤ .0039). At week 24, 76.4% and 70.2% of the alirocumab group achieved LDL cholesterol <1.8 mmol/L in the T2D and T1D populations (P < .0001), respectively. Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration. Treatment‐emergent adverse events were observed in 64.5% of alirocumab‐ vs 64.1% of placebo‐treated individuals (overall population). Conclusions Alirocumab produced significant LDL cholesterol reductions in participants with insulin‐treated diabetes regardless of diabetes type, and was generally well tolerated. Concomitant administration of alirocumab and insulin did not raise any safety concerns (NCT02585778). PMID:28905478

Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH.

PubMed

Caballero, Francisco; Fernández, Anna; De Lacy, Antonio M; Fernández-Checa, Jose C; Caballería, Juan; García-Ruiz, Carmen

2009-04-01

Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. Filipin staining, indicative of FC accumulation, and real-time PCR analyses were performed in 31 NAFLD patients and in seven controls. All NASH patients (n=14) and 4 out of 17 patients with steatosis exhibited filipin staining compared to controls (0 out of 7 subjects with normal liver histology and BMI). Sterol regulatory element-binding protein-2 (SREBP-2) mRNA levels were 7- and 3-fold higher in NASH and steatosis patients, respectively, compared to controls. Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients. Fatty acid synthase (FAS) and SREBP-1c expression were not significantly induced in NAFLD, while ATP-binding cassette sub-family G member 1 (ABCG1), a transporter involved in cholesterol egress, and acyl-CoA-cholesterol acyltransferase mRNA levels were modestly increased (1.5- to 2.5-fold, p<0.05), regardless of fibrosis. Interestingly, mRNA levels of steroidogenic acute regulatory protein (StAR), a mitochondrial-cholesterol transporting polypeptide, increased 7- and 15-fold in steatosis and NASH patients, respectively, compared to controls. FC increases in NASH and correlates with SREBP-2 induction. Moreover, StAR overexpression in NASH suggests that mitochondrial FC may be a player in disease progression and a novel target for intervention.

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

PubMed

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Identification of a Novel Hypocholesterolemic Protein, Major Royal Jelly Protein 1, Derived from Royal Jelly

PubMed Central

Asai, Saori; Kusada, Mio; Watanabe, Suzuyo; Kawashima, Takuji; Nakamura, Tadashi; Shimada, Masaya; Goto, Tsuyoshi; Nagaoka, Satoshi

2014-01-01

Royal jelly (RJ) intake lowers serum cholesterol levels in animals and humans, but the active component in RJ that lowers serum cholesterol level and its molecular mechanism are unclear. In this study, we set out to identify the bile acid-binding protein contained in RJ, because dietary bile acid-binding proteins including soybean protein and its peptide are effective in ameliorating hypercholesterolemia. Using a cholic acid-conjugated column, we separated some bile acid-binding proteins from RJ and identified the major RJ protein 1 (MRJP1), MRJP2, and MRJP3 as novel bile acid-binding proteins from RJ, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Purified MRJP1, which is the most abundant protein of the bile acid-binding proteins in RJ, exhibited taurocholate-binding activity in vitro. The micellar solubility of cholesterol was significantly decreased in the presence of MRJP1 compared with casein in vitro. Liver bile acids levels were significantly increased, and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein tended to increase by MRJP1 feeding compared with the control. CYP7A1 mRNA and protein levels were significantly increased by MRJP1 tryptic hydrolysate treatment compared with that of casein tryptic hydrolysate in hepatocytes. MRJP1 hypocholesterolemic effect has been investigated in rats. The cholesterol-lowering action induced by MRJP1 occurs because MRJP1 interacts with bile acids induces a significant increase in fecal bile acids excretion and a tendency to increase in fecal cholesterol excretion and also enhances the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ. Interestingly, MRJP1 exhibits greater hypocholesterolemic activity than the medicine β-sitosterol in rats. PMID:25144734

Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling

PubMed Central

Qin, Li; Yang, Yun-bo; Yang, Yi-xin; Zhu, Neng; Gong, Yong-zhen; Zhang, Cai-ping; Li, Shun-xiang; Liao, Duan-fang

2014-01-01

Aim: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro. Methods: VSMCs of SD rats were cultured in the presence of Chol:MβCD (10 μg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence. Results: Treatment with Chol:MβCD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:MβCD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 μmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 μmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did. Conclusion: Ezetimibe suppresses cholesterol accumulation in rat VSMCs in vitro by regulating SREBP-1 and caveolin-1 expression, possibly via the MAPK signaling pathway. PMID:25087996

Hypogonadism Makes Dyslipidemia in Klinefelter's Syndrome.

PubMed

Lee, Hyo Serk; Park, Chan Woo; Lee, Joong Shik; Seo, Ju Tae

2017-11-01

Klinefelter's syndrome (KS) is a genetic syndrome that presents with hypogonadism and is associated with metabolic syndrome. Patients demonstrating hypogonadism show a greater prevalence of metabolic syndrome due to changes in body composition. We aimed to determine the association between KS and dyslipidemia. The KS group comprised 55 patients who visited the infertility clinic for an infertility evaluation and were confirmed as having a diagnosis of KS. The control group comprised 120 patients who visited the clinic for health screening. Patient characteristics were compared between the two groups with respect to height, weight, body mass index (BMI), testosterone, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels. Height and weight were significantly greater in patients belonging to the KS group, but no statistically significant difference was found with respect to the BMI. Testosterone levels in patients belonging to the KS group were significantly lower compared to the control group (2.4 ± 2.6 vs. 5.2 ± 1.8 ng/mL, P < 0.001). Compared to the control group, TG levels in patients belonging to the KS group were increased (134.9 ± 127.8 vs. 187.9 ± 192.1 mg/dL, P = 0.004) and HDL cholesterol was significantly decreased (51.2 ± 22.0 vs. 44.0 ± 9.5 mg/dL, P = 0.009). LDL cholesterol and total cholesterol were not significantly different between the two groups (P = 0.076 and P = 0.256, respectively). Significant differences were noted between patients belonging to the KS group and normal control group with respect to elevated TG and decreased HDL cholesterol levels. © 2017 The Korean Academy of Medical Sciences.

PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

PubMed

Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

2017-09-01

Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

PubMed

Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

2017-08-01

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [ 3 H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels.

PubMed

Keleş, Telat; Akar Bayram, Nihal; Kayhan, Tuğba; Canbay, Alper; Sahin, Deniz; Durmaz, Tahir; Ozdemir, Ozcan; Aydoğdu, Sinan; Diker, Erdem

2008-12-01

In this study, we aimed at comparing the effects of standard once daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered every other day on serum lipids and high sensitive C-reactive protein (hs-CRP) levels. Sixty-one patients with serum total cholesterol levels of above 200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130 mg/dl were included in this prospective, randomized study. The patients were randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20 mg atorvastatin every other day (every other day treatment) groups. Before the treatment and at each visit, serum lipids and hs-CRP levels of all the patients were measured. Statistical analyses were performed Chi-square, unpaired t and two-way repeated measurements ANOVA tests. In the every other day treatment group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first month (p<0.01). At the end of three months there was further decrease of 10.2% in LDL-cholesterol levels when compared to 1 month levels (p>0.05). The LDL cholesterol levels of the group receiving 20 mg atorvastatin every day was reduced by %41 by the end of 1 month (p<0.01). At the end of three months, the difference between the changes in the all lipid parameters of the two groups was not found to be of statistical significance. In the group receiving the medication every other day, there was a 21% decrease in hs-CRP levels compared to the basal measurements at the end of first month (p<0.05). In the group, receiving the medication every day the decrease in hs-CRP levels at the end of one month was more striking (37%, p<0.05). However, the effects of both treatment arms on hs-CRP levels, did not differ significantly (p>0.05). Alternate-day dosing of atorvastatin causes a significant lipid-lowering and antiinflammatory effects similar to that of daily administration and yet may provide some cost savings.

Identification of the Best Anthropometric Predictors of Serum High- and Low-Density Lipoproteins Using Machine Learning.

PubMed

Lee, Bum Ju; Kim, Jong Yeol

2015-09-01

Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are associated with risk factors for various diseases and are related to anthropometric measures. However, controversy remains regarding the best anthropometric indicators of the HDL and LDL cholesterol levels. The objectives of this study were to identify the best predictors of HDL and LDL cholesterol using statistical analyses and two machine learning algorithms and to compare the predictive power of combined anthropometric measures in Korean adults. A total of 13,014 subjects participated in this study. The anthropometric measures were assessed with binary logistic regression (LR) to evaluate statistically significant differences between the subjects with normal and high LDL cholesterol levels and between the subjects with normal and low HDL cholesterol levels. LR and the naive Bayes algorithm (NB), which provides more reasonable and reliable results, were used in the analyses of the predictive power of individual and combined measures. The best predictor of HDL was the rib to hip ratio (p =< 0.0001; odds ratio (OR) = 1.895; area under curve (AUC) = 0.681) in women and the waist to hip ratio (WHR) (p =< 0.0001; OR = 1.624; AUC = 0.633) in men. In women, the strongest indicator of LDL was age (p =< 0.0001; OR = 1.662; AUC by NB = 0.653 ; AUC by LR = 0.636). Among the anthropometric measures, the body mass index (BMI), WHR, forehead to waist ratio, forehead to rib ratio, and forehead to chest ratio were the strongest predictors of LDL; these measures had similar predictive powers. The strongest predictor in men was BMI (p =< 0.0001; OR = 1.369; AUC by NB = 0.594; AUC by LR = 0.595 ). The predictive power of almost all individual anthropometric measures was higher for HDL than for LDL, and the predictive power for both HDL and LDL in women was higher than for men. A combination of anthropometric measures slightly improved the predictive power for both HDL and LDL cholesterol. The best indicator for HDL and LDL might differ according to the type of cholesterol and the gender. In women, but not men, age was the variable that strongly predicted HDL and LDL cholesterol levels. Our findings provide new information for the development of better initial screening tools for HDL and LDL cholesterol.

The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes

PubMed Central

Fredericks, William J.; Sepulveda, Jorge; Lal, Priti; Tomaszewski, John E.; Lin, Ming-Fong; McGarvey, Terry; Rauscher, Frank J; Malkowicz, S. Bruce

2013-01-01

Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phenotype of CRPC and the TERE1 tumor suppressor protein, a prenyltransferase that synthesizes vitamin K-2, which is a potent endogenous ligand for the SXR nuclear hormone receptor. We show that 50% of primary and metastatic prostate cancer specimens exhibit a loss of TERE1 expression and we establish a correlation between TERE1 expression and cholesterol in the LnCaP-C81 steroidogenic cell model of the CRPC. LnCaP-C81 cells also lack TERE1 protein, and show elevated cholesterol synthetic rates, higher steady state levels of cholesterol, and increased expression of enzymes in the de novo cholesterol biosynthetic pathways than the non-steroidogenic prostate cancer cells. C81 cells also show decreased expression of the SXR nuclear hormone receptor and a panel of directly regulated SXR target genes that govern cholesterol efflux and steroid catabolism. Thus, a combination of increased synthesis, along with decreased efflux and catabolism likely underlies the CRPC phenotype: SXR might coordinately regulate this phenotype. Moreover, TERE1 controls synthesis of vitamin K-2, which is a potent endogenous ligand for SXR activation, strongly suggesting a link between TERE1 levels, K-2 synthesis and SXR target gene regulation. We demonstrate that following ectopic TERE1 expression or induction of endogenous TERE1, the elevated cholesterol levels in C81 cells are reduced. Moreover, reconstitution of TERE1 expression in C81 cells reactivates SXR and switches on a suite of SXR target genes that coordinately promote both cholesterol efflux and androgen catabolism. Thus, loss of TERE1 during tumor progression reduces K-2 levels resulting in reduced transcription of SXR target genes. We propose that TERE1 controls the CPRC phenotype by regulating the endogenous levels of Vitamin K-2 and hence the transcriptional control of a suite of steroidogenic genes via the SXR receptor. These data implicate the TERE1 protein as a previously unrecognized link affecting cholesterol and androgen accumulation that could govern acquisition of the CRPC phenotype. PMID:23919967

Taiwanese female vegetarians have lower lipoprotein-associated phospholipase A2 compared with omnivores.

PubMed

Chen, Chih-Wei; Lin, Chih-Ta; Lin, Ying-Lung; Lin, Tin-Kwang; Lin, Chin-Lon

2011-01-01

Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores. One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP). Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 μmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 μmol/min/mL vs. 20.22 8.13 10-3 μmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity. In addition to lower total cholesterol, LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.

Potential effects of reclassifying CKD as a coronary heart disease risk equivalent in the US population.

PubMed

Foster, Meredith C; Rawlings, Andreea M; Marrett, Elizabeth; Neff, David; Grams, Morgan E; Kasiske, Bertram L; Willis, Kerry; Inker, Lesley A; Coresh, Josef; Selvin, Elizabeth

2014-05-01

Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. Nationally representative cross-sectional study. 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. CKD and LDL cholesterol defined using a single laboratory value. Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of the hypolipidemic effects of coconut water and lovastatin in rats fed fat-cholesterol enriched diet.

PubMed

Sandhya, V G; Rajamohan, T

2008-12-01

The coconut water presents a series of nutritional and therapeutic properties, being a natural, acid and sterile solution, which contains several biologically active components, l-arginine, ascorbic acid, minerals such as calcium, magnesium and potassium, which have beneficial effects on lipid levels. Recent studies in our laboratory showed that both tender and mature coconut water feeding significantly (P<0.05) reduced hyperlipidemia in cholesterol fed rats [Sandhya, V.G., Rajamohan, T., 2006. Beneficial effects of coconut water feeding on lipid metabolism in cholesterol fed rats. J. Med. Food 9, 400-407]. The current study evaluated the hypolipidemic effect of coconut water (4ml/100g body weight) with a lipid lowering drug, lovastatin (0.1/100g diet) in rats fed fat-cholesterol enriched diet ad libitum for 45 days. Coconut water or lovastatin supplementation lowered the levels of serum total cholesterol, VLDL+LDL cholesterol, triglycerides and increased HDL cholesterol in experimental rats (P<0.05). Coconut water feeding decreased activities of hepatic lipogenic enzymes and increased HMG CoA reductase and lipoprotein lipase activity (P<0.05). Incorporation of radioactive acetate into free and ester cholesterol in the liver were higher in coconut water treated rats. Coconut water supplementation increased hepatic bile acid and fecal bile acids and neutral sterols (P<0.05). Coconut water has lipid lowering effect similar to the drug lovastatin in rats fed fat-cholesterol enriched diet.

Hypoxia-ischemia brain damage disrupts brain cholesterol homeostasis in neonatal rats.

PubMed

Yu, Z; Li, S; Lv, S H; Piao, H; Zhang, Y H; Zhang, Y M; Ma, H; Zhang, J; Sun, C K; Li, A P

2009-08-01

The first 3 weeks of life is the peak time of oligodendrocytes development and also the critical period of cholesterol increasing dramatically in central nervous system in rats. Neonatal hypoxia-ischemia (HI) brain damage happening in this period may disturb the brain cholesterol balance as well as white matter development. To test this hypothesis, postnatal day 7 (P7) Sprague-Dawley rats were subjected to HI insult. Cholesterol concentrations from brain and plasma were measured. White matter integrity was evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining and electron microscopy. Brain TNF-alpha and IL-6 levels were also measured. HI-induced brain cholesterol, but not the plasma cholesterol, levels decreased significantly during the first three days after HI compared with naïve and sham operated rats (p<0.05). Obvious hypomyelination was indicated by marked reductions in MBP immunostaining on both P10 and P14 (p<0.01) and less and thinner myelinated axons were detected on P21 by electron microscopy observation. High expressions of brain TNF-alpha and IL-6 12 h after HI (p<0.05) were also observed. The present work provides evidence that HI insult destroyed brain cholesterol homeostasis, which might be important in the molecular pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol balance may be effective for the recovery of white matter function. Georg Thieme Verlag KG Stuttgart New York.

Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats.

PubMed

Del Bas, Josep Maria; Fernández-Larrea, Juan; Blay, Mayte; Ardèvol, Anna; Salvadó, Maria Josepa; Arola, Lluis; Bladé, Cinta

2005-03-01

Moderate consumption of red wine reduces risk of death from cardiovascular disease. The polyphenols in red wine are ultimately responsible for this effect, exerting antiatherogenic actions through their antioxidant capacities and modulating intracellular signaling pathways and transcriptional activities. Lipoprotein metabolism is crucial in atherogenesis, and liver is the principal organ controlling lipoprotein homeostasis. This study was intended to identify the primary effects of procyanidins, the most abundant polyphenols in red wine, on both plasma lipoprotein profile and the expression of genes controlling lipoprotein homeostasis in the liver. We show that procyanidins lowered plasma triglyceride, free fatty acids, apolipoprotein B (apoB), LDL-cholesterol and nonHDL:nonLDL-cholesterol levels and slightly increased HDL-cholesterol. Liver mRNA levels of small heterodimer partner (SHP), cholesterol 7alpha-hydroxylase (CYP7A1), and cholesterol biosynthetic enzymes increased, whereas those of apoAII, apoCI, and apoCIII decreased. Lipoprotein lipase (LPL) mRNA levels increased in muscle and decreased in adipose tissue. In conclusion, procyanidins improve the atherosclerotic risk index in the postprandial state, inducing in the liver the overexpression of CYP7A1 (suggesting an increase of cholesterol elimination via bile acids) and SHP, a nuclear receptor emerging as a key regulator of lipid homeostasis at the transcriptional level. These results could explain, at least in part, the beneficial long-term effects associated with moderate red wine consumption.

The fat and protein fractions of freshwater clam ( Corbicula fluminea) extract reduce serum cholesterol and enhance bile acid biosynthesis and sterol excretion in hypercholesterolaemic rats fed a high-cholesterol diet.

PubMed

Chijimatsu, Takeshi; Umeki, Miki; Okuda, Yuji; Yamada, Koji; Oda, Hiroaki; Mochizuki, Satoshi

2011-02-01

We investigated whether the fat and protein fractions of freshwater clam (Corbicula fluminea) extract (FCE) could ameliorate hypercholesterolaemia in rats fed a high-cholesterol diet. We also explored the mechanism and the components that exert the hypocholesterolaemic effect of FCE. The doses of the fat and protein fractions were equivalent to those in 30 % FCE. The fat and protein fractions of FCE, two major components of FCE, significantly reduced the serum and hepatic cholesterol levels. The fat fraction more strongly reduced serum cholesterol levels than the same level of total FCE. The excretion of faecal neutral sterols increased in rats fed the total the FCE and the fat fraction of FCE. On the other hand, faecal bile acid levels were greater in rats fed the total FCE and the fat and protein fractions of FCE than in control animals. The hepatic gene expression of ATP-binding cassette transporter G5 and cholesterol 7α-hydroxylase was up-regulated by the administration of the total FCE and both the fat and protein fractions of FCE. These results showed that the fat and protein fractions of FCE had hypocholesterolaemic properties, and that these effects were greater with the fat fraction than with the protein fraction. The present study indicates that FCE exerts its hypocholesterolaemic effects through at least two different mechanisms, including enhanced excretion of neutral sterols and up-regulated biosynthesis of bile acids.

Evaluation of Cholesterol as a Biomarker for Suicidality in a Veteran Sample.

PubMed

Reuter, Chuck; Caldwell, Barbara; Basehore, Heather

2017-08-01

A reduction in total cholesterol may alter the microviscosity of the brain-cell-membrane, reducing serotonin receptor exposure. The resulting imbalance between serotonin and dopamine may lead to an increased risk for suicidality. The objective of this research was to evaluate total cholesterol as a biological marker for suicidality in a sample of US military veterans. The study population consisted of veterans who received care at the Coatesville Veterans Affairs Medical Center (VAMC) and were included in the Suicide Prevention Coordinator's database for having suicidal ideation with evidence of escalating intent, a documented suicide attempt, or committed suicide between 2009 and 2015. The veterans' medical data were obtained from the facility's computerized patient record system. The final sample was 188 observations from 128 unique veterans. Veterans with total cholesterol levels below 168 mg/dl appeared to have a higher suicide risk than those with higher levels. The cholesterol levels of veterans reporting suicidal ideation or attempt were significantly lower than the group reporting neither [F(2, 185) = 30.19, p < .001]. When data from multiple visits were available, veterans reporting suicidal ideation or attempt had experienced a significant (20%) decrease in cholesterol levels from an earlier visit in which they did not report suicidality. A latent class analysis revealed that among other differences, suicidal veterans were younger, leaner, and had more anxiety, sleep problems, and higher education than those being seen for an issue unrelated to suicidality. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of Hibiscus sabdariffa L. on serum lipids: a systematic review and meta-analysis.

PubMed

Aziz, Zoriah; Wong, Su Yuen; Chong, Nyuk Jet

2013-11-25

Prevention of cardiovascular disease by modifying its major risk factors, including serum cholesterol levels, is an important strategy. Hibiscus sabdariffa L. has been promoted for reducing cholesterol levels, but its reported impact on cholesterol levels has been inconsistent. The study aimed to assess systematically the evidence and quality of current research on the effect of Hibiscus sabdariffa L. on blood lipids and its adverse effects. Electronic databases were searched up to June 2013 for relevant randomised controlled trials (RCTs). Journals and conference proceedings were also searched. The quality of the selected trials was assessed using the Cochrane Risk of Bias Assessment Tool. The efficacy results of similar studies were pooled if they used the same comparator. Outcomes examined were levels of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. Six studies involving 474 subjects met our inclusion criteria. These studies varied in terms of the types of interventions, comparators used, and duration of trials. Overall, Hibiscus sabdariffa L. did not produce any significant effect on any of the outcomes examined, when compared with placebo, black tea or diet. With short-term use it is well tolerated. The available evidence from RCTs does not support the efficacy of Hibiscus sabdariffa L. in lowering serum lipids. Further rigorously designed trials with larger sample sizes are warranted to confirm the effects of HS on serum lipids. © 2013 Elsevier Ireland Ltd. All rights reserved.

Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients

PubMed Central

2010-01-01

Multiple Sclerosis (MS) patients present a decrease of antioxidants and neuroprotective and immunoregulatory vitamins and an increase of total homocysteine (tHcy), cholesterol (CHL), HDL-cholesterol, and of cellular stress markers, variably associated with the different phases of the disease. We compared the blood levels of uric acid, folic acid, vitamins B12, A, and E, tHcy, CHL, HDL-cholesterol, and triglycerides in forty MS patients during a phase of clinical inactivity with those of eighty healthy controls, matched for age and sex. We found higher levels of tHcy (p = 0.032) and of HDL-cholesterol (p = 0.001) and lower levels of vitamin E (p = 0.001) and the ratio vitamin E/CHL (p = 0.001) in MS patients. In conclusion, modifications of some biochemical markers of cell damage were detected in MS patients during a phase of clinical inactivity. PMID:20163740

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

PubMed

Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 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. Lemongrass oil (100 and 200 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 atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Further LDL cholesterol lowering through targeting PCSK9 for coronary artery disease.

PubMed

Cao, Guoqing; Qian, Yue-Wei; Kowala, Mark C; Konrad, Robert J

2008-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density lipoprotein receptor (LDLR) levels in vitro and in vivo. Thus PCSK9 has emerged as an important player modulating LDLR levels and plasma LDL cholesterol. Furthermore, PCSK9 deficiency leads to significantly lowered LDL cholesterol levels in humans and provides dramatic protection against coronary heart disease. We review here the current understanding of PCSK9 and its potential as a therapeutic target through which to reduce LDL cholesterol for prevention and treatment of coronary heart disease.

Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

PubMed Central

2010-01-01

Background Previous observations demonstrate that Cftr-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased de novo synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by de novo cholesterol synthesis. Methods Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age. Results Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTRinh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. De novo cholesterol synthesis contributes to membrane cholesterol accessibility. Conclusions The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in de novo cholesterol synthesis to restore membrane content. PMID:20487541

Essentially All Excess Fibroblast Cholesterol Moves from Plasma Membranes to Intracellular Compartments

PubMed Central

Lange, Yvonne; Ye, Jin; Steck, Theodore L.

2014-01-01

It has been shown that modestly increasing plasma membrane cholesterol beyond its physiological set point greatly increases the endoplasmic reticulum and mitochondrial pools, thereby eliciting manifold feedback responses that return cell cholesterol to its resting state. The question arises whether this homeostatic mechanism reflects the targeting of cell surface cholesterol to specific intracellular sites or its general equilibration among the organelles. We now show that human fibroblast cholesterol can be increased as much as two-fold from 2-hydroxypropyl-β-cyclodextrin without changing the size of the cell surface pool. Rather, essentially all of the added cholesterol disperses rapidly among cytoplasmic membranes, increasing their overall cholesterol content by as much as five-fold. We conclude that the level of plasma membrane cholesterol is normally at capacity and that even small increments above this physiological set point redistribute essentially entirely to intracellular membranes, perhaps down their chemical activity gradients. PMID:25014655

Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model

PubMed Central

2012-01-01

Background Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4–30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model. Methods Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output. Results In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P < 0.05, Student’s t-test). We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w) high cholesterol diet-treated cardiac output significant at P < 0.05, 1-way ANOVA). Using this model, we found hawthorn leaves and flowers significantly reduce intravascular cholesterol levels (P < 0.05, 1-way ANOVA) and interact with cholesterol to impact cardiac output in hypercholesterolemic fish (2-way ANOVA, P < 0.05 for interaction effect). Conclusions The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels. Further, our observation that hawthorn leaves and flowers interact with cholesterol to impact cardiac output indicates that the physiological effects of hawthorn may depend on diet. PMID:22824306

Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster.

PubMed

Spady, D K; Dietschy, J M

1985-07-01

The liver plays a key role in the regulation of circulating levels of low density lipoproteins (LDL) because it is both the site for the production of and the major organ for the degradation of this class of lipoproteins. In this study, the effects of feeding polyunsaturated or saturated triacylglycerols on receptor-dependent and receptor-independent hepatic LDL uptake were measured in vivo in the hamster. In control animals, receptor-dependent LDL transport manifested an apparent Km value of 85 mg/dl (plasma LDL-cholesterol concentration) and reached a maximum transport velocity of 131 micrograms of LDL-cholesterol/hr per g, whereas receptor-independent uptake increased as a linear function of plasma LDL levels. Thus, at normal plasma LDL-cholesterol concentrations, the hepatic clearance rate of LDL equaled 120 and 9 microliter/hr per g by receptor-dependent and receptor-independent mechanisms, respectively. As the plasma LDL-cholesterol was increased, the receptor-dependent (but not the receptor-independent) component declined. When cholesterol (0.12%) alone or in combination with polyunsaturated triacylglycerols was fed for 30 days, receptor-dependent clearance was reduced to 36-42 microliter/hr per g, whereas feeding of cholesterol plus saturated triacylglycerols essentially abolished receptor-dependent LDL uptake (5 microliter/hr per g). When compared to the appropriate kinetic curves, these findings indicated that receptor-mediated LDL transport was suppressed approximately equal to 30% by cholesterol feeding alone and this was unaffected by the addition of polyunsaturated triacylglycerols to the diet. In contrast, receptor-dependent uptake was suppressed approximately equal to 90% by the intake of saturated triacylglycerols. As compared to polyunsaturated triacylglycerols, the intake of saturated lipids was also associated with significantly higher plasma LDL-cholesterol concentrations and lower levels of cholesteryl esters in the liver.

Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

PubMed

Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

2017-06-01

Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Mean age  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Potential use of cholesterol lipoprotein profile to confirm obesity status in dogs.

PubMed

Mori, Nobuko; Lee, Peter; Kondo, Kazuo; Kido, Toshimi; Saito, Terumasa; Arai, Toshiro

2011-04-01

A common sign of obesity, in dogs, is hyperlipidemia, which is characterized by hypercholesterolemia and/or hypertriglycemia. Hyperlipidemia can be caused by a quantitative increase in circulating lipoproteins (LP) or by a higher lipid concentration in the various LP classes. In this study, we sought to determine whether aberrations occur with cholesterol lipoprotein profile, especially with sub HDL-cholesterol fraction % in obese dogs. Using clinically healthy and disease free (no overt signs) body condition score classified obese dogs, of all ages, we attempted to determine the influence of age, gender and obesity status on cholesterol lipoprotein profiling. Overall, no aberration in pattern was observed in obese dogs <8 years of age. However, in older obese animals (≥8 years of age), the general aberration pattern to cholesterol lipoprotein observed was that a significant decrease in HDL2 and 3 fraction % occurs with a concomitant increase in either HDL1-Cho or VLDL and LDL -Cho fraction % depending on gender. Linear regression analysis indicated that obesity status appears to significantly affect total cholesterol, HDL2 and 3-Cho, VLDL and LDL-Cho levels (P=0.02, 0.046, and 0.045, respectively), whereas it is borderline with HDL1-Cho (P=0.062). On the other hand, age significantly influenced TG, Total cholesterol, and HDL1-Cho levels (P=0.009, 0.006, and 0.002, respectively), while gender influenced VLDL and LDL-Cho (P=0.024) level. Therefore, aberrations in cholesterol lipoprotein profile pattern might be of potential use to assess and diagnose obesity status, in conjunction with BCS, especially of older overweight animals which might be considered borderline obese. © Springer Science+Business Media B.V. 2011

Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.

PubMed

Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Montagnani, Marco; Locatelli, Marcello; Diani, Erika; Giavarini, Flavio; Caruso, Donatella; Roda, Enrico; Roda, Aldo; Sirtori, Cesare R; Chiesa, Giulia

2012-10-01

Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines. © 2012 John Wiley & Sons A/S.

Plant sterol ester diet supplementation increases serum plant sterols and markers of cholesterol synthesis, but has no effect on total cholesterol levels.

PubMed

Weingärtner, Oliver; Bogeski, Ivan; Kummerow, Carsten; Schirmer, Stephan H; Husche, Constanze; Vanmierlo, Tim; Wagenpfeil, Gudrun; Hoth, Markus; Böhm, Michael; Lütjohann, Dieter; Laufs, Ulrich

2017-05-01

This double-blind, randomized, placebo-controlled, cross-over intervention-study was conducted in healthy volunteers to evaluate the effects of plant sterol ester supplemented margarine on cholesterol, non-cholesterol sterols and oxidative stress in serum and monocytes. Sixteen volunteers, average age 34 years, with no or mild hypercholesterolemia were subjected to a 4 week period of daily intake of 3g plant sterols per day supplied via a supplemented margarine on top of regular eating habits. After a wash-out period of one week, volunteers switched groups. Compared to placebo, a diet supplementation with plant sterols increased serum levels of plant sterols such as campesterol (+0.16±0.19mg/dL, p=0.005) and sitosterol (+0.27±0.18mg/dL, p<0.001) and increased markers of cholesterol synthesis such as desmosterol (+0.05±0.07mg/dL, p=0.006) as well as lathosterol (+0.11±0.16mg/dL, p=0.012). Cholesterol serum levels, however, were not changed significantly (+18.68±32.6mg/dL, p=0.052). These findings could not be verified in isolated circulating monocytes. Moreover, there was no effect on monocyte activation and no differences with regard to redox state after plant sterol supplemented diet. Therefore, in a population of healthy volunteers with no or mild hypercholesterolemia, consumption of plant sterol ester supplemented margarine results in increased concentrations of plant sterols and cholesterol synthesis markers without affecting total cholesterol in the serum, activation of circulating monocytes or redox state. Copyright © 2016 Elsevier Ltd. All rights reserved.

National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report.

PubMed

Jacobson, Terry A; Ito, Matthew K; Maki, Kevin C; Orringer, Carl E; Bays, Harold E; Jones, Peter H; McKenney, James M; Grundy, Scott M; Gill, Edward A; Wild, Robert A; Wilson, Don P; Brown, W Virgil

2015-01-01

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy.

PubMed

Guo, Yitian; Luo, Hanwen; Wu, Yimeng; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2018-05-22

Epidemiological surveys suggest that adult hypercholesterolemia has an intrauterine origin and exhibits gender differences. Our previous study demonstrated that adult rats with intrauterine growth retardation (IUGR) offspring rats induced by prenatal caffeine exposure (PCE) had a higher serum total cholesterol (TCH) level. In this study, we aimed to analyze the influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy. Pregnant rats were administered caffeine (120 mg/kg d) from gestational day 11 until delivery. Offspring rats fed a normal diet or a high-fat diet (HFD) were euthanized at postnatal week 24, and blood and liver samples were collected. The results showed that PCE could increase the serum levels of TCH and low-density lipoprotein-cholesterol (LDL-C), and the hepatic expression of HMG CoA reductase (HMGCR) and apolipoprotein B (ApoB), but decreased the high-density lipoprotein-cholesterol (HDL-C) level and the hepatic expression of scavenger receptor B1 (SR-B1) and LDL receptor (LDLR). Furthermore, PCE, HFD and gender interact with each other to influence the serum cholesterol phenotype and expression of hepatic cholesterol metabolic genes. These results suggest that the hypercholesterolemia in adult offspring rats induced by PCE mainly resulted from enhanced synthesis and the weakened reverse transport of cholesterol in the liver, furthermore HFD could aggravate this effect, which is caused by hepatic cholesterol metabolic disorders. Moreover, cholesterol metabolism in female rats was more sensitive to neuroendocrine changes and HFD than that in males. This study confirmed the influencing factors (such as a HFD and female gender) of hypercholesterolemia in IUGR offspring providing theoretical and experimental bases for the effective prevention of fetal-originated hypercholesterolemia. Copyright © 2018 Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

2002-01-01

During hibernation, fat is known to be the preferred source of energy. A detailed analysis of different phospholipids, as well as free and esterified cholesterol, was conducted to investigate lipid abnormalities during hibernation. The levels of total phospholipids and total cholesterol in the serum of black bears were found to increase significantly in hibernation as compared with the active state. Both free and esterified cholesterol were increased in the hibernating state in comparison with the active state (P < 0.05). The percentage increase during hibernation was more in free cholesterol (57%) than in esterified cholesterol (27%). Analysis of subclasses of serum phospholipids showed that choline containing phospholipids, i.e., sphingomyelin (SPG) (14%) and phosphatidylcholine (PC) (76%), are the major phospholipids in the serum of bear. The minor phospholipids included 8% of phosphatidylserine (PS) + phosphatidylinositol (PI), while phosphatidylethanolamine (PE) was only 2% of the total phospholipids. A comparison of phospholipid subclasses showed that PC, PS + PI and SPG were significantly increased, while PE was significantly decreased (P < 0.05) in the hibernating state as compared with the active state in black bears. These results suggest that the catabolism of phospholipids and cholesterol is decreased during hibernation in black bears, leading to their increased levels in the hibernating state as compared with the active state. In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears. It is proposed that the increase of these lipids may be due to the altered metabolism of lipoproteins that are responsible for the clearance of the lipids. ?? 2002 E??ditions scientifiques et me??dicales Elsevier SAS and Socie??te?? franc??aise de biochimie et biologie mole??culaire. All rights reserved.

Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality.

PubMed

Ulmer, Hanno; Kelleher, Cecily; Diem, Günter; Concin, Hans

2004-01-01

To assess the impact of sex-specific patterns in cholesterol levels on all-cause and cardiovascular mortality in the Vorarlberg Health Monitoring and Promotion Programme (VHM&PP). In this study, 67413 men and 82237 women (aged 20-95 years) underwent 454448 standardized examinations, which included measures of blood pressure, height, weight, and fasting samples for cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and glucose in the 15-year period 1985-1999. Relations between these variables and risk of death were analyzed using two approaches of multivariate analyses (Cox proportional hazard and GEE models). Patterns of cholesterol levels showed marked differences between men and women in relation to age and cause of death. The role of high cholesterol in predicting death from coronary heart disease could be confirmed in men of all ages and in women under the age of 50. In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases. Triglycerides > 200 mg/dl had an effect in women 65 years and older but not in men. This large-scale population-based study clearly demonstrates the contrasting patterns of cholesterol level in relation to risk, particularly among those less well studied previously, that is, women of all ages and younger people of both sexes. For the first time, we demonstrate that the low cholesterol effect occurs even among younger respondents, contradicting the previous assessments among cohorts of older people that this is a proxy or marker for frailty occurring with age.

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases.

PubMed

Keever-Taylor, Carolyn A; Heimfeld, Shelly; Steinmiller, Kaitlyn C; Nash, Richard A; Sullivan, Keith M; Czarniecki, Christine W; Granderson, Tomeka C; Goldstein, Julia S; Griffith, Linda M

2017-09-01

To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases-sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with "Critical Elements." We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34 + HPC) graft specifications included ≥70% viable CD34 + cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34 + HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 10 6 viable CD34 + cells/kg (range, 3.9 to 12.8)  for HALT-MS and 5.6 × 10 6 viable CD34 + cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34 + cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34 + /kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34 + HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34 + cells. Manufacturing of Auto-CD34 + HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets. Published by Elsevier Inc.

Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

ERIC Educational Resources Information Center

Cohen, Jonathan C.; And Others

1988-01-01

Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Lipid profiles and determinants of total cholesterol and hypercholesterolaemia among 25–74 year-old urban and rural citizens of the Yangon Region, Myanmar: a cross-sectional study

PubMed Central

Htet, Aung Soe; Aung, Wai Phyo; Moe Myint, Aye Nyein; Aye, Win Thuzar; Wai, Myint Myint; Nu, Than Than; Hla, Ei Mon; Soe, Pyone Pyone; Tun, Nan Wut Yi; Angela, Naw; Khaing, Mya Mya; Htoo, Aung Kyaw; Tun, Soe; Thitsar, Pai; Lwin, Theeoo; Wai, San San; Aung, Thi Thi; Thant, Khin Aye; Aung Po, Wai Wai; Gauzam, Seng Taung; Naing, Tun Tun; Tun, Thet Min; Myint, Khin San; Oo, Kyi Kyi; Mang, Nang Kee Myu; Naing, Soe Moe; Zaw, Ko Ko; Bjertness, Marius Bergsmark; Sherpa, Lhamo Yangchen; Oo, Win Myint; Stigum, Hein; Bjertness, Espen

2017-01-01

Objective The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol. Design Two cross-sectional studies using the WHO STEPS methodology. Setting Both the urban and rural areas of the Yangon Region, Myanmar. Participants A total of 1370 men and women aged 25–74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded. Results Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001). Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women. Conclusion The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed. PMID:29146640

Low childhood high density lipoprotein cholesterol levels and subsequent risk for chronic inflammatory bowel disease.

PubMed

Voutilainen, Markku; Hutri-Kähönen, Nina; Tossavainen, Päivi; Sipponen, Taina; Pitkänen, Niina; Laitinen, Tomi; Jokinen, Eero; Rönnemaa, Tapani; Viikari, Jorma S A; Raitakari, Olli T; Juonala, Markus

2018-04-01

Several genetic and environmental risk factors have been linked to chronic inflammatory bowel disease (IBD). The incidence of IBD has significantly increased in developed countries during last decades. The aim of the present study was to examine childhood risk factors for subsequent IBD diagnosis in a longitudinal cohort study of children and adolescents. A Finnish study population consisting of 3551 children and adolescents originally evaluated as part of the Cardiovascular Risk in Young Finns study in 1980. At baseline, participant BMI, insulin, lipid, C-reactive protein and blood pressure levels, socioeconomic position, dietary habits, and physical activity, were evaluated. In addition, information was gathered on rural residency, severe infections, breast feeding, parental smoking and birth weight. Subsequent IBD diagnosis status was evaluated based on nationwide registries on hospitalisations and drug imbursement decisions. Altogether, 49 participants (1.4%) had IBD diagnosed during the 34 years of register follow-up, of which 31 had ulcerative colitis, 12 Crohn's disease and 6 undetermined colitis. In univariate analyses, significant correlations were observed between childhood HDL-cholesterol (risk ratio (95% CI) for 1-SD change (0.58 (0.42-0.79)) and CRP concentrations (1.20 (1.01-1.43)) with IBD. The inverse association between HDL-cholesterol and IBD remained significant (0.57 (0.39-0.82)) in a multivariable model including data on age, sex and CRP. In addition, a weighted genetic z-score of 71 single nucleotide polymorphisms associated with elevated HDL-cholesterol levels was significantly lower in IBD patients, P=0.01). Low childhood HDL-cholesterol levels are associated with subsequent IBD diagnosis. In addition, a genetic risk score associated with low HDL-cholesterol levels predict later IBD suggesting that HDL-cholesterol metabolism might have a role in the pathogenesis of IBD. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The effect of sauna bathing on lipid profile in young, physically active, male subjects.

PubMed

Gryka, Dorota; Pilch, Wanda; Szarek, Marta; Szygula, Zbigniew; Tota, Łukasz

2014-08-01

The aim of the study was to evaluate effects of Finnish sauna bathing on lipid profile in healthy, young men. Sixteen male subjects (20-23 years) were subjected to 10 sauna bathing sessions in a Finnish sauna every 1 or 2 days. The mean sauna temperature was 90±2°C, while humidity was 5-16%. Each session consisted of three 15-minute parts and a 2-minute cool-down between them. The following measurements were taken before and after the sauna sessions: body mass, heart rate, body skinfold thickness. The percentage fat content and then, the lean body mass were calculated. Total cholesterol, triacylglycerols, lipoprotein cholesterol LDL and HDL were measured in blood samples. A statistically significant decrease of total cholesterol and LDL cholesterol was observed during 3 weeks of sauna treatment and in the week afterwards. A significant decline in triacylglycerols was found directly after the 1st and 24 h directly after the 10th sauna session. After the 10th sauna session the level of HDL cholesterol remained slightly increased, but this change was not statistically significant. A decrease in blood plasma volume was found directly after the 1st and the last sauna bathing session due to perspiration. An adaptive increase in blood plasma volume was also found after the series of 10 sauna sessions. Ten complete sauna bathing sessions in a Finnish sauna caused a reduction in total cholesterol and LDL cholesterol fraction levels during the sessions and a gradual return of these levels to the initial level during the 1st and the 2nd week after the experiment. A small, statistically insignificant increase in HDL-C level and a transient decline in triacylglycerols were observed after those sauna sessions. The positive effect of sauna on lipid profile is similar to the effect that can be obtained through a moderate-intensity physical exercise.

Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro.

PubMed

Lammel Lindemann, Jan A; Angajala, Anusha; Engler, David A; Webb, Paul; Ayers, Stephen D

2014-05-05

Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor β1 (TRβ1) in liver to regulate metabolic gene sets. In rodents, one important TH regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450 family, which enhances cholesterol to bile acid conversion and plays a crucial role in regulation of serum cholesterol levels. Current models suggest, however, that Cyp7a1 has lost the capacity to respond to THs in humans. We were prompted to re-examine TH effects on cholesterol metabolic genes in human liver cells by a recent study of a synthetic TH mimetic which showed that serum cholesterol reductions were accompanied by increases in a marker for bile acid synthesis in humans. Here, we show that TH effects upon cholesterol metabolic genes are almost identical in mouse liver, mouse and human liver primary cells and human hepatocyte cell lines. Moreover, Cyp7a1 is a direct TR target gene that responds to physiologic TR levels through a set of distinct response elements in its promoter. These findings suggest that THs regulate cholesterol to bile acid conversion in similar ways in humans and rodent experimental models and that manipulation of hormone signaling pathways could provide a strategy to enhance Cyp7a1 activity in human patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

PubMed

Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

2016-01-01

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

Associations of systemic sphingolipids with measures of hepatic function in liver cirrhosis are related to cholesterol.

PubMed

Krautbauer, Sabrina; Wiest, Reiner; Liebisch, Gerhard; Buechler, Christa

2017-07-01

Lipoprotein particles are composed of various lipid classes including cholesterol and sphingolipids, and are low in serum of patients with liver cirrhosis. Hepatic decompensation is associated with a further decline of lipoproteins. Aim of the present work was to evaluate whether ceramide and sphingomyelin species are similarly changed in patients with liver cirrhosis and whether these variations are related to systemic cholesterol levels. In a cohort of 45 patients suffering from liver cirrhosis, cholesteryl ester species and subsequently total cholesterol were identified to be negatively associated with model of end stage liver disease (MELD) score. Indeed, the negative correlations of ceramide (Cer) and sphingomyelin (SM) species with MELD score, bilirubin and anti-thrombin 3 were non-significant after adjustment for cholesterol. Cer/SM ratios of species with identical acyl chains were not related to Child-Pugh or MELD score indicating that both lipids are comparably changed. Further, cholesterol levels and concentrations of all sphingolipids measured were similar in systemic, hepatic vein and portal vein blood. Cholesterol and distinct sphingolipids were similar before and 3 months after insertion of a transjugular intrahepatic portosystemic shunt while hexosylceramide 24:1 was significantly induced. It is concluded that analysis of distinct systemic sphingolipid species is not superior to measurement of cholesterol as non-invasive marker of hepatic injury in patients with liver cirrhosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9[S

PubMed Central

Ason, Brandon; Tep, Samnang; Davis, Harry R.; Xu, Yiming; Tetzloff, Glen; Galinski, Beverly; Soriano, Ferdie; Dubinina, Natalya; Zhu, Lei; Stefanni, Alice; Wong, Kenny K.; Tadin-Strapps, Marija; Bartz, Steven R.; Hubbard, Brian; Ranalletta, Mollie; Sachs, Alan B.; Flanagan, W. Michael; Strack, Alison; Kuklin, Nelly A.

2011-01-01

Reducing circulating LDL-cholesterol (LDL-c) reduces the risk of cardiovascular disease in people with hypercholesterolemia. Current approaches to reduce circulating LDL-c include statins, which inhibit cholesterol synthesis, and ezetimibe, which blocks cholesterol absorption. Both elevate serum PCSK9 protein levels in patients, which could attenuate their efficacy by reducing the amount of cholesterol cleared from circulation. To determine whether PCSK9 inhibition could enhance LDL-c lowering of both statins and ezetimibe, we utilized small interfer­ing RNAs (siRNAs) to knock down Pcsk9, together with ezetimibe, rosuvastatin, and an ezetimibe/rosuvastatin combination in a mouse model with a human-like lipid profile. We found that ezetimibe, rosuvastatin, and ezetimibe/rosuvastatin combined lower serum cholesterol but induce the expression of Pcsk9 as well as the Srebp-2 hepatic cholesterol biosynthesis pathway. Pcsk9 knockdown in combination with either treatment led to greater reductions in serum non-HDL with a near-uniform reduction of all LDL-c subfractions. In addition to reducing serum cholesterol, the combined rosuvastatin/ezetimibe/Pcsk9 siRNA treatment exhibited a significant reduction in serum APOB protein and triglyceride levels. Taken together, these data provide evidence that PCSK9 inhibitors, in combination with current therapies, have the potential to achieve greater reductions in both serum cholesterol and triglycerides. PMID:21262787

Atherogenic potentials of some Nigerian meals.

PubMed

Eyong, E U; Umoh, I B; Ogu, T I; Edet, E E; Eteng, M U; Igiri, A O

2007-01-01

The atherogenic potentials of peeled grated cocoyam (Xanthosoma maffafa scot) "ekpang nkukwo", pounded yam (Discorea spp) with plain soup "afia efere", and plantain porridge (Musa paradisiaca) "iwuk ukom" meals were investigated. The three meals were fed to three different groups of albino rats of Wistar strain for a period of twenty eight days. A fourth group which served as control was feed with normal rat pellet. The mean total plasma cholesterol level in the pounded yam with plain soup fed group was significantly lower [P < 0.05] when compared to the control and peeled grated cocoyam fed groups. The mean total plasma triglyceride (MTPTG) level in the pounded yam with plain soup fed group was significantly lower [P < 0.05] when compared to the control group. However the MTPTG level in the peeled grated cocoyam and plantain porridge fed groups were comparable to control. The mean HDL-cholesterol level in the peeled grated cocoyam and plantain fed groups were comparable control. The mean LDL-cholesterol level in the peeled grated cocoyam and plantain porridge fed groups was significantly lower [P < 0.05] than the control group. The LDL-cholesterol and VLDL-cholesterol in the pounded yam with plain soup fed group was significantly lower [P < 0.05] when compared to control. These findings suggest low atherogenic potentials of the pounded yam with plain soup meal compared to the peeled grated cocoyam and plantain porridge meals.

Response of osteocalcin and insulin resistance after a hypocaloric diet in obese patients.

PubMed

de Luis, D A; Perez Castrillon, J L; Aller, R; Izaola, O; Bachiller, C

2015-06-01

Osteocalcin is a hormone with a complex cross-talk between adipose tissue and the skeleton. The aim of the present study was to explore the change of osteocalcin, insulin resistance, and adipocytokines after hypocaloric diet in obese patients. A population of 178 obese patients was analyzed. At basal time and 2 months after the dietary intervention, weight, fat mass, body mass index, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, leptin, adiponectin, IL-6, TNF alpha and osteocalcin levels were measured. After dietary treatment, BMI, weight, fat mass, waist circumference, waist to hip ratio, systolic pressure, glucose, HOMA, triglycerides, total cholesterol, leptin and LDL cholesterol decreased significantly. Osteocalcin levels have a significant decrease after weight loss (Osteocalcin (ng/ml); 9.76 ± 5.3 vs 9.31 ± 4.1: p < 0.05). In correlation analysis, a negative association was detected among osteocalcin and age, BMI, fat mass, glucose, C reactive protein, interleukin-6. In the linear regression with age-, sex-, BMI, fat mass- and insulin- adjusted, only C reactive protein concentrations are related with osteocalcin levels -0.21 (CI 95%: -0.40 -0.009). Osteocalcin decreased after a weight loss treatment. Moreover, osteocalcin levels, before and after treatment, were related in a negative way with CRP fat mass, body mass index, age and glucose levels.

Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of serum in mice lacking Pcsk9

PubMed Central

2013-01-01

Background Studies in animals showed that PCSK9 is involved in HDL metabolism. We investigated the molecular mechanism by which PCSK9 regulates HDL cholesterol concentration and also whether Pcsk9 inactivation might affect cholesterol efflux capacity of serum and atherosclerotic fatty streak volume. Methods Mass spectrometry and western blot were used to analyze the level of apolipoprotein E (APOE) and A1 (APOA1). A mouse model overexpressing human LDLR was used to test the effect of high levels of liver LDLR on the concentration of HDL cholesterol and APOE-containing HDL subfractions. Pcsk9 knockout males lacking LDLR and APOE were used to test whether LDLR and APOE are necessary for PCSK9-mediated HDL cholesterol regulation. We also investigated the effects of Pcsk9 inactivation on cholesterol efflux capacity of serum using THP-1 and J774.A1 macrophage foam cells and atherosclerotic fatty streak volume in the aortic sinus of Pcsk9 knockout males fed an atherogenic diet. Results APOE and APOA1 were reduced in the same HDL subfractions of Pcsk9 knockout and human LDLR transgenic male mice. In Pcsk9/Ldlr double-knockout mice, HDL cholesterol concentration was lower than in Ldlr knockout mice and higher than in wild-type controls. In Pcsk9/Apoe double-knockout mice, HDL cholesterol concentration was similar to that of Apoe knockout males. In Pcsk9 knockout males, THP-1 macrophage cholesterol efflux capacity of serum was reduced and the fatty streak lesion volume was similar to wild-type controls. Conclusions In mice, LDLR and APOE are important factors for PCSK9-mediated HDL regulation. Our data suggest that, although LDLR plays a major role in PCSK9-mediated regulation of HDL cholesterol concentration, it is not the only mechanism and that, regardless of mechanism, APOE is essential. Pcsk9 inactivation decreases the HDL cholesterol concentration and cholesterol efflux capacity in serum, but does not increase atherosclerotic fatty streak volume. PMID:23883163

Hypolipidaemic effects of Citrullus colocynthis L. in rabbits.

PubMed

Daradka, Haytham; Almasad, Motasem M; Qazan, Walid Sh; El-Banna, Nasser M; Samara, Omar H

2007-08-15

Aim of this research to study the effect of Citrullus colocynthis (70% EtOH) extract on lipid profile on Rabbits. The plant extract was orally administered to the atherogenic rabbits (atherogenic diet + cholesterol powder supplement 400 mg/kg/body weight/day dissolved in 5 mL coconut oil) at dose of 1.2 g kg(-1) body weight/day. During the hall period of the experiment blood was collected and serum was analyzed for lipid profile. Animals were sacrificed; the heart and the liver were collected and kept at -20 degrees C until assayed. Biochemical analysis of blood serum and tissue (liver and heart muscle) level were made for cholesterol, Phospholipids and triglycerides. In addition blood serum was analyzed further for HDL-Cholesterol. All the results were statistically analyzed using students t-test. Hypolipidaemic nature of Citrullus colocynthis (70% EtOH) extract was studied in hyperlipidaemic Rabbits. The increased cholesterol levels were brought to normal by administration of Citrullus colocynthis. Serum cholesterol levels dropped from 940.7 to 230.41 (75.55%) and further to 119.2 (87.32%) by the end of the experiment. Similarly, phospholipids and triglycerides levels were observed to be also reduced. The tissues lipids profiles of liver and heart muscle showed similar changes in those noticed in serum lipids. Citrullus colocynthis possesses active hypolipidaemic constituents.

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels.

PubMed

Cox, C; Sutherland, W; Mann, J; de Jong, S; Chisholm, A; Skeaff, M

1998-09-01

The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.

Simultaneous Determination of Oxysterols, Cholesterol and 25-Hydroxy-Vitamin D3 in Human Plasma by LC-UV-MS

PubMed Central

Narayanaswamy, Rohini; Iyer, Vignesh; Khare, Prachi; Bodziak, Mary Lou; Badgett, Darlene; Zivadinov, Robert; Weinstock-Guttman, Bianca; Rideout, Todd C.; Ramanathan, Murali; Browne, Richard W.

2015-01-01

Background Oxysterols are promising biomarkers of neurodegenerative diseases that are linked with cholesterol and vitamin D metabolism. There is an unmet need for methods capable of sensitive, and simultaneous quantitation of multiple oxysterols, vitamin D and cholesterol pathway biomarkers. Methods A method for simultaneous determination of 5 major oxysterols, 25-hydroxy vitamin D3 and cholesterol in human plasma was developed. Total oxysterols were prepared by room temperature saponification followed by solid phase extraction from plasma spiked with deuterated internal standards. Oxysterols were resolved by reverse phase HPLC using a methanol/water/0.1% formic acid gradient. Oxysterols and 25-hydroxy vitamin D3 were detected with atmospheric pressure chemical ionization mass spectrometry in positive ion mode; in-series photodiode array detection at 204nm was used for cholesterol. Method validation studies were performed. Oxysterol levels in 220 plasma samples from healthy control subjects, multiple sclerosis and other neurological disorders patients were quantitated. Results Our method quantitated 5 oxysterols, cholesterol and 25-hydroxy vitamin D3 from 200 μL plasma in 35 minutes. Recoveries were >85% for all analytes and internal standards. The limits of detection were 3-10 ng/mL for oxysterols and 25-hydroxy vitamin D3 and 1 μg/mL for simultaneous detection of cholesterol. Analytical imprecision was <10 %CV for 24(S)-, 25-, 27-, 7α-hydroxycholesterol (HC) and cholesterol and ≤15 % for 7-keto-cholesterol. Multiple Sclerosis and other neurological disorder patients had lower 27-hydroxycholesterol levels compared to controls whereas 7α-hydroxycholesterol was lower specifically in Multiple Sclerosis. Conclusion The method is suitable for measuring plasma oxysterols levels in human health and disease. Analysis of human plasma indicates that the oxysterol, bile acid precursors 7α-hydroxycholesterol and 27-hydroxycholesterol are lower in Multiple Sclerosis and may serve as potential biomarkers of disease. PMID:25875771

Cholesterol removal from adult skeletal muscle impairs excitation–contraction coupling and aging reduces caveolin-3 and alters the expression of other triadic proteins

PubMed Central

Barrientos, Genaro; Llanos, Paola; Hidalgo, Jorge; Bolaños, Pura; Caputo, Carlo; Riquelme, Alexander; Sánchez, Gina; Quest, Andrew F. G.; Hidalgo, Cecilia

2015-01-01

Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation–contraction (E–C) coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum (SR) calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not SR membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX) activity and protein content of NOX2 subunits (p47phox and gp91phox), implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs E–C coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged animals. PMID:25914646

Proposition of decision limits for serum lipids in Brazilian children aged one to 13 years.

PubMed

Slhessarenko, Natasha; Fontes, Cor J F; Slhessarenko, Maria Eduarda; Azevedo, Raymundo S; Andriolo, Adagmar

2018-03-09

To determine decision limits for total cholesterol, LDL-cholesterol, non-HDL cholesterol, HDL-cholesterol, and triglycerides in healthy children and adolescents from Cuiabá, Brazil. This was a cross-sectional study of 1866 healthy children and adolescents randomly selected from daycare centers and public schools in Cuiabá. The desirable levels of serum lipids were defined using the classic criteria, i.e., total cholesterol, LDL-cholesterol, non-HDL cholesterol, and triglycerides levels below the P75 percentile, and HDL-c above the P10 percentile. For CT, P75 was: 160mg/dL for the age range of 1 to <3 years, 170mg/dL for ≥3 to <9 years, and 176mg/dL for ≥9 to <13 years. For non-HDL cholesterol, it was 122mg/dL for the age range of 1 to <13 years. For LDL-c, it was 104mg/dL at the age range of 1 to <9 years and 106mg/dL from ≥9 to <13 years. For TG, it was 127mg/dL from 1 to <2 years; 98mg/dL from ≥2 to <6 years; and 92mg/dL from ≥6 to <13 years. As for HDL-cholesterol, P10 was 24mg/dL, 28mg/dL, 32mg/dL, and 36mg/dL, for the age ranges of 1 to <2 years, ≥2 to <3 years, ≥3 to <4 years, and ≥4 to <13 years, respectively. The decision limits for the serum lipid levels defined in this study differed from those observed in the current Brazilian and North-American guidelines, especially because it differentiates between the age ranges. Using these decision limits in clinical practice will certainly contribute to improve the diagnostic accuracy for dyslipidemia in this population group. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.

PubMed

Nicolas, Xavier; Djebli, Nassim; Rauch, Clémence; Brunet, Aurélie; Hurbin, Fabrice; Martinez, Jean-Marie; Fabre, David

2018-05-03

Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations. As a second step, we then developed the current population pharmacokinetic/pharmacodynamic model using an indirect response model with a Hill coefficient, parameterized with increasing low-density lipoprotein cholesterol elimination, to relate alirocumab concentrations to low-density lipoprotein cholesterol values. The population pharmacokinetic/pharmacodynamic model allowed the characterization of the pharmacokinetic/pharmacodynamic properties of alirocumab in the target population and estimation of individual low-density lipoprotein cholesterol levels and derived pharmacodynamic parameters (the maximum decrease in low-density lipoprotein cholesterol values from baseline and the difference between baseline low-density lipoprotein cholesterol and the pre-dose value before the next alirocumab dose). Significant parameter-covariate relationships were retained in the model, with a total of ten covariates (sex, age, weight, free baseline PCSK9, total time-varying PCSK9, concomitant statin administration, total baseline PCSK9, co-administration of high-dose statins, disease status) included in the final population pharmacokinetic/pharmacodynamic model to explain between-subject variability. Nevertheless, the high number of covariates included in the model did not have a clinically meaningful impact on model-derived pharmacodynamic parameters. This model successfully allowed the characterization of the population pharmacokinetic/pharmacodynamic properties of alirocumab in its target population and the estimation of individual low-density lipoprotein cholesterol levels.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

PubMed

Maki, K C; Lawless, A L; Kelley, K M; Kaden, V N; Geiger, C J; Palacios, O M; Dicklin, M R

2017-01-01

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL 1+2 -C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6  versus 0.7 mg/dl, respectively, P=0.016). CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

Association between blood cholesterol and sodium intake in hypertensive women with excess weight.

PubMed

Padilha, Bruna Merten; Ferreira, Raphaela Costa; Bueno, Nassib Bezerra; Tassitano, Rafael Miranda; Holanda, Lidiana de Souza; Vasconcelos, Sandra Mary Lima; Cabral, Poliana Coelho

2018-04-01

Restricted sodium intake has been recommended for more than 1 century for the treatment of hypertension. However, restriction seems to increase blood cholesterol. In women with excess weight, blood cholesterol may increase even more because of insulin resistance and the high lipolytic activity of adipose tissue.The aim of this study was to assess the association between blood cholesterol and sodium intake in hypertensive women with and without excess weight.This was a cross-sectional study with hypertensive and nondiabetic women aged 20 to 59 years, recruited at the primary healthcare units of Maceio, Alagoas, Brazilian Northeast. Excess weight was defined as body mass index (BMI) ≥25.0 kg/m. Sodium intake was estimated by the 24-hour urinary excretion of sodium. Blood cholesterol was the primary outcome investigated by this study, and its relationship with sodium intake and other variables was assessed by Pearson correlation and multivariate linear regression using a significance level of 5%.This study included 165 hypertensive women. Of these, 135 (81.8%) were with excess weight. The mean sodium intake was 3.7 g (±1.9) and 3.4 g (±2.4) in hypertensive women with and without excess weight, respectively. The multiple normal linear regression models fitted to the "blood cholesterol" in the 2 groups reveal that for the group of hypertensive women without excess weight only 1 independent variable "age" is statistically significant to explain the variability of the blood cholesterol levels. However, for the group of hypertensive women with excess weight, 2 independent variables, age and sodium intake, can statistically explain variations of the blood cholesterol levels.Blood cholesterol is statistically inversely related to sodium intake for hypertensive women with excess weight, but it is not statistically related to sodium intake for hypertensive women without excess weight.

Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) [Lp(a)], Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examinati...

Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis

PubMed Central

Berglund, Lars; Brunzell, John D.; Goldberg, Anne C.; Goldberg, Ira J.; Stalenhoef, Anton

2013-01-01

While there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research. PMID:24840268

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

PubMed

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.

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

PubMed

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

2000-09-01

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

Longitudinal Changes in Serum Levels of Angiopoietin-Like Protein 6 and Selenoprotein P After Gastric Bypass Surgery.

PubMed

Lim, Jisun; Park, Hye Soon; Lee, Seul Ki; Jang, Yeon Jin; Lee, Yeon Ji; Heo, Yoonseok

2016-04-01

Bariatric surgery has beneficial effects on weight loss and metabolic profiles. Recent evidence suggests that liver-derived hepatokines play a role in the pathophysiology of metabolic diseases. However, few studies have reported longitudinal changes in hepatokines after gastric bypass surgery. We investigated changes in the serum levels of angiopoietin-like protein 6 (Angptl6) and selenoprotein P after gastric bypass surgery. We followed 10 patients who were treated with gastric bypass for weight loss. We measured metabolic parameters and the serum levels of Angptl6 and selenoprotein P before, 1 month after, and 9 months after surgery. We investigated the changes in those hepatokines after surgery and the associations between changes in Angptl6 and selenoprotein P, respectively, and metabolic parameters. Body mass index decreased linearly. Levels of hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), total cholesterol, triglyceride, LDL cholesterol, and Angptl6 were significantly lower 1 and 9 months after surgery. Fasting plasma glucose was normal throughout the study. Fasting insulin decreased 1 month after surgery but increased 9 months post-surgery. Levels of selenoprotein P increased linearly. Significant correlations were detected between the levels of Angptl6 and LDL cholesterol and fasting insulin. Changes in Angptl6 levels were significantly correlated with changes in total cholesterol and LDL cholesterol. Selenoprotein P levels were inversely correlated with GGT, and changes in selenoprotein P were inversely correlated with changes in homeostasis model assessment for insulin resistance (HOMA-IR). Our results suggest that gastric bypass may alter the serum levels of hepatokines independent of weight loss, and these changes are related to certain hepatic metabolic changes.

Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.

PubMed

Rollefstad, S; Ikdahl, E; Hisdal, J; Olsen, I C; Holme, I; Hammer, H B; Smerud, K T; Kitas, G D; Pedersen, T R; Kvien, T K; Semb, A G

2015-07-01

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease. © 2015, American College of Rheumatology.

Early steps in steroidogenesis: intracellular cholesterol trafficking

PubMed Central

Miller, Walter L.; Bose, Himangshu S.

2011-01-01

Steroid hormones are made from cholesterol, primarily derived from lipoproteins that enter cells via receptor-mediated endocytosis. In endo-lysosomes, cholesterol is released from cholesterol esters by lysosomal acid lipase (LAL; disordered in Wolman disease) and exported via Niemann-Pick type C (NPC) proteins (disordered in NPC disease). These diseases are characterized by accumulated cholesterol and cholesterol esters in most cell types. Mechanisms for trans-cytoplasmic cholesterol transport, membrane insertion, and retrieval from membranes are less clear. Cholesterol esters and “free” cholesterol are enzymatically interconverted in lipid droplets. Cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins. Cytochrome P450scc (CYP11A1) then initiates steroidogenesis by converting cholesterol to pregnenolone on the inner mitochondrial membrane (IMM). Acute steroidogenic responses are regulated by cholesterol delivery from OMM to IMM, triggered by the steroidogenic acute regulatory protein (StAR). Chronic steroidogenic capacity is determined by CYP11A1 gene transcription. StAR mutations cause congenital lipoid adrenal hyperplasia, with absent steroidogenesis, potentially lethal salt loss, and 46,XY sex reversal. StAR mutations initially destroy most, but not all steroidogenesis; low levels of StAR-independent steroidogenesis are lost later due to cellular damage, explaining the clinical findings. Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis. PMID:21976778

Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

PubMed

Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

2013-01-01

Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial.

PubMed

Ulven, Stine M; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob J; Telle-Hansen, Vibeke H; Skjetne, Anne J; Raael, Ellen; Sheikh, Navida A; Holck, Marianne; Torvik, Kristin; Lamglait, Amandine; Thyholt, Kari; Byfuglien, Marte G; Granlund, Linda; Andersen, Lene F; Holven, Kirsten B

2016-10-01

The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25-70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was -9 and -11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.

Relationship between serum cholesterol and Graves' orbitopathy (GO): a confirmatory study.

PubMed

Lanzolla, G; Sabini, E; Profilo, M A; Mazzi, B; Sframeli, A; Rocchi, R; Menconi, F; Leo, M; Nardi, M; Vitti, P; Marcocci, C; Marinò, M

2018-06-19

It has been suggested that high cholesterol represents a risk factor for Graves' orbitopathy (GO). In a recent cross-sectional study, a correlation between cholesterol and the presence of GO was found in patients with a Graves' disease (GD) of recent onset. To confirm this observation, we conducted a retrospective investigation in consecutive patients with GD. The primary outcome was the relationship between the presence of GO and low-density lipoprotein (LDL)-cholesterol. The design entailed the inclusion of consecutive patients with a GD of recent onset, with or without GO, who came to our observation to receive radioiodine over a period of 6 months, and a stratification aimed at having two homogeneous group of patients in terms of thyroid function. A total of 86 patients fulfilled the inclusion and evaded the exclusion criteria. All patients underwent an ophthalmological assessment and serum lipids were measured. Serum levels of LDL-cholesterol were significantly higher in patients with GO (135.3 ± 41.3 mg/dL) compared with those without GO (106.6 ± 23.9 mg/dL, P = 0.0007). In a similar manner, serum levels of total cholesterol were higher in patients with GO (211.6 ± 44.0 mg/dL) than in those without GO (176.0 ± 27.2 mg/dL, P = 0.0001). There was no relationship between GO severity and activity and cholesterol. There was no relationship between GO and high-density lipoprotein-cholesterol or triglycerides. Our study confirms a relationship between the presence of GO and cholesterol in patients with GD of recent onset. Whether lowering of cholesterol ameliorates, GO remains to be established.

Influence of Cholesterol on the Oxygen Permeability of Membranes: Insight from Atomistic Simulations.

PubMed

Dotson, Rachel J; Smith, Casey R; Bueche, Kristina; Angles, Gary; Pias, Sally C

2017-06-06

Cholesterol is widely known to alter the physical properties and permeability of membranes. Several prior works have implicated cell membrane cholesterol as a barrier to tissue oxygenation, yet a good deal remains to be explained with regard to the mechanism and magnitude of the effect. We use molecular dynamics simulations to provide atomic-resolution insight into the influence of cholesterol on oxygen diffusion across and within the membrane. Our simulations show strong overall agreement with published experimental data, reproducing the shapes of experimental oximetry curves with high accuracy. We calculate the upper-limit transmembrane oxygen permeability of a 1-palmitoyl,2-oleoylphosphatidylcholine phospholipid bilayer to be 52 ± 2 cm/s, close to the permeability of a water layer of the same thickness. With addition of cholesterol, the permeability decreases somewhat, reaching 40 ± 2 cm/s at the near-saturating level of 62.5 mol % cholesterol and 10 ± 2 cm/s in a 100% cholesterol mimic of the experimentally observed noncrystalline cholesterol bilayer domain. These reductions in permeability can only be biologically consequential in contexts where the diffusional path of oxygen is not water dominated. In our simulations, cholesterol reduces the overall solubility of oxygen within the membrane but enhances the oxygen transport parameter (solubility-diffusion product) near the membrane center. Given relatively low barriers to passing from membrane to membrane, our findings support hydrophobic channeling within membranes as a means of cellular and tissue-level oxygen transport. In such a membrane-dominated diffusional scheme, the influence of cholesterol on oxygen permeability is large enough to warrant further attention. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Alternative Fuels Data Center: Texas Puts a New Spin on Mowing

Science.gov Websites

halt on Ozone Action Days, and petroleum use is reduced by about 100,000 gallons per year. " On -level ozone pollution, prompting the state to declare Ozone Action Days. On these days, residents and produce much lower emissions than gasoline mowers do, and they can be used on Ozone Action Days. CTCC

75 FR 36012 - Fisheries of the Northeastern United States; 2010 Specifications for the Spiny Dogfish Fishery

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... be lower than historic levels due to reduced maternal size and a skewed male-to-female sex ratio in... male-to-female sex ratio in the population. Therefore, the FY 2010 commercial quota is being increased... and implemented in 2000 in order to halt large-scale depletion of reproductively mature female spiny...

Lipid profile and thyroid hormone status in the last trimester of pregnancy in single-humped camels (Camelus dromedarius).

PubMed

Omidi, Arash; Sajedi, Zhila; Montazer Torbati, Mohammad Bagher; Ansari Nik, Hossein

2014-04-01

Changes in lipid metabolism have been shown to occur during pregnancy. The thyroid hormones affect lipid metabolism. The present study was carried out to find out whether the last trimester of pregnancy affects thyroid hormones, thyroid-stimulating hormone (TSH), lipid, and lipoprotein profile in healthy dromedary camels. Twenty clinical healthy dromedary camels aged between 4-5 years were divided into two equal groups: (1) pregnant camels in their last trimester of pregnancy and (2) non-pregnant age-matched controls. Thyroid function tests were carried out by measuring serum levels of TSH, free thyroxin (fT4), total thyroxin (T4), free triiodothyronine (fT3), and total triiodothyronine (T3) by commercially available radio immunoassay kits. Total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) cholesterol were analyzed using enzymatic/spectrophotometric methods while low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL), and total lipid (TL) were calculated using Friedewald's and Raylander's formula, respectively. Serum levels of TSH and thyroid hormones except fT4 did not show any significant difference between pregnant and non-pregnant camels. fT4 level was lower in the pregnant camels (P < 0.05). Serum levels of total cholesterol, triglyceride, total lipid, LDL cholesterol, HDL cholesterol, and VLDL did not show significant difference between pregnant and non-pregnant camels. All of these variables in pregnant camels were higher than non-pregnant. Based on the results of this study, the fetus load may not alter the thyroid status of the camel and the concentrations of thyroid hormones were not correlated with TSH and lipid profile levels in the healthy pregnant camels.

The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein.

PubMed

Takeuchi, Hidekazu; Sata, Masataka

2012-01-01

To study the relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein. A retrospective, cross-sectional study. Tokushima University Hospital area. A retrospective study of 46 patients (nine inpatients and 37 outpatients) with angina pectoris or arrhythmias who were seen at Tokushima University Hospital Cardiovascular Division and had measurements of their BNP, fatty acid and lipid profile. The average age of patients was 57±17 years, and 39% were male subjects. BNP, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), apolipoproteinA1, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), apolipoprotein C2, apolipoprotein C3, apolipoprotein E, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The baseline characteristics of the patients were shown in table 1 and the data of lipoprotein were shown in table 2. Table 3 shows the relationship among BNP, cholesterol and lipoprotein. The authors found significant negative correlation between serum levels of BNP and ApoA2 (figure 1; r=-0.458, p=0.001), serum levels of BNP and ApoB (figure 2; r=-0.328, p=0.026) and serum levels of BNP and TC (figure 3; r=-0.383, p=0.010). There is a possibility that dietary EPA and DHA may modulate cardiac mitochondrial and autonomic nervous system dysfunction via fatty-acids-PPARs-PTEN-PI3K/Akt-SREBPs system and affect serum BNP levels indirectly. BNP had significant negative correlation with ApoA2, ApoB and TC. The findings suggest that increasing serum levels of ApoA2, ApoB and TC may have an effect on improving heart function. But the mechanism is presently unclear.

The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein

PubMed Central

Takeuchi, Hidekazu; Sata, Masataka

2012-01-01

Objective To study the relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein. Design A retrospective, cross-sectional study. Setting Tokushima University Hospital area. Patients A retrospective study of 46 patients (nine inpatients and 37 outpatients) with angina pectoris or arrhythmias who were seen at Tokushima University Hospital Cardiovascular Division and had measurements of their BNP, fatty acid and lipid profile. The average age of patients was 57±17 years, and 39% were male subjects. Main outcome measures BNP, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), apolipoproteinA1, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), apolipoprotein C2, apolipoprotein C3, apolipoprotein E, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. Results The baseline characteristics of the patients were shown in table 1 and the data of lipoprotein were shown in table 2. Table 3 shows the relationship among BNP, cholesterol and lipoprotein. The authors found significant negative correlation between serum levels of BNP and ApoA2 (figure 1; r=−0.458, p=0.001), serum levels of BNP and ApoB (figure 2; r=−0.328, p=0.026) and serum levels of BNP and TC (figure 3; r=-0.383, p=0.010). There is a possibility that dietary EPA and DHA may modulate cardiac mitochondrial and autonomic nervous system dysfunction via fatty-acids-PPARs-PTEN-PI3K/Akt-SREBPs system and affect serum BNP levels indirectly. Conclusion BNP had significant negative correlation with ApoA2, ApoB and TC. The findings suggest that increasing serum levels of ApoA2, ApoB and TC may have an effect on improving heart function. But the mechanism is presently unclear. PMID:27326018

The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism

PubMed Central

Calderon-Dominguez, Maria; Gil, Gregorio; Medina, Miguel Angel; Pandak, William M.; Rodríguez-Agudo, Daniel

2014-01-01

Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracelular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis. PMID:24440759

Sexual Selection Halts the Relaxation of Protamine 2 among Rodents

PubMed Central

Lüke, Lena; Vicens, Alberto; Serra, Francois; Luque-Larena, Juan Jose; Dopazo, Hernán; Roldan, Eduardo R. S.; Gomendio, Montserrat

2011-01-01

Sexual selection has been proposed as the driving force promoting the rapid evolutionary changes observed in some reproductive genes including protamines. We test this hypothesis in a group of rodents which show marked differences in the intensity of sexual selection. Levels of sperm competition were not associated with the evolutionary rates of protamine 1 but, contrary to expectations, were negatively related to the evolutionary rate of cleaved- and mature-protamine 2. Since both domains were found to be under relaxation, our findings reveal an unforeseen role of sexual selection: to halt the degree of degeneration that proteins within families may experience due to functional redundancy. The degree of relaxation of protamine 2 in this group of rodents is such that in some species it has become dysfunctional and it is not expressed in mature spermatozoa. In contrast, protamine 1 is functionally conserved but shows directed positive selection on specific sites which are functionally relevant such as DNA-anchoring domains and phosphorylation sites. We conclude that in rodents protamine 2 is under relaxation and that sexual selection removes deleterious mutations among species with high levels of sperm competition to maintain the protein functional and the spermatozoa competitive. PMID:22216223

Intermittent fasting during Ramadan causes a transient increase in total, LDL, and HDL cholesterols and hs-CRP in ethnic obese adolescents.

PubMed

Radhakishun, Nalini; Blokhuis, Charlotte; van Vliet, Mariska; von Rosenstiel, Ines; Weijer, Olivier; Heymans, Martijn; Beijnen, Jos; Brandjes, Dees; Diamant, Michaela

2014-08-01

The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P < 0.05). Six weeks after Ramadan, all parameters returned to baseline levels. In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan.

Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens.

PubMed

Afrose, Sadia; Hossain, Md Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada

2010-01-01

This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of (14)C from 1-(14)C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver.

Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens

PubMed Central

Afrose, Sadia; Hossain, Md. Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada

2010-01-01

This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of 14C from 1-14C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver. PMID:21490913

Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS.

PubMed

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N; Dokras, Anuja

2014-05-01

Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. A case control study was performed at an academic PCOS center. Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

PubMed Central

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N.

2014-01-01

Context: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. Objective: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. Design and Setting: A case control study was performed at an academic PCOS center. Patients: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. Main Outcome Measures: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Results: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population. PMID:24512495

A genetic variant in the LDLR promoter is responsible for part of the LDL-cholesterol variability in primary hypercholesterolemia

PubMed Central

2014-01-01

Background GWAS have consistently revealed that LDLR locus variability influences LDL-cholesterol in general population. Severe LDLR mutations are responsible for familial hypercholesterolemia (FH). However, most primary hypercholesterolemias are polygenic diseases. Although Cis-regulatory regions might be the cause of LDL-cholesterol variability; an extensive analysis of the LDLR distal promoter has not yet been performed. We hypothesized that genetic variants in this region are responsible for the LDLR association with LDL-cholesterol found in GWAS. Methods Four-hundred seventy-seven unrelated subjects with polygenic hypercholesterolemia (PH) and without causative FH-mutations and 525 normolipemic subjects were selected. A 3103 pb from LDLR (-625 to +2468) was sequenced in 125 subjects with PH. All subjects were genotyped for 4 SNPs (rs17242346, rs17242739, rs17248720 and rs17249120) predicted to be potentially involved in transcription regulation by in silico analysis. EMSA and luciferase assays were carried out for the rs17248720 variant. Multivariable linear regression analysis using LDL-cholesterol levels as the dependent variable were done in order to find out the variables that were independently associated with LDL-cholesterol. Results The sequencing of the 125 PH subjects did not show variants with minor allele frequency ≥ 10%. The T-allele from g.3131C > T (rs17248720) had frequencies of 9% (PH) and 16.4% (normolipemic), p < 0.00001. Studies of this variant with EMSA and luciferase assays showed a higher affinity for transcription factors and an increase of 2.5 times in LDLR transcriptional activity (T-allele vs C-allele). At multivariate analysis, this polymorphism with the lipoprotein(a) and age explained ≈ 10% of LDL-cholesterol variability. Conclusion Our results suggest that the T-allele at the g.3131 T > C SNP is associated with LDL-cholesterol levels, and explains part of the LDL-cholesterol variability. As a plausible cause, the T-allele produces an increase in LDLR transcriptional activity and lower LDL-cholesterol levels. PMID:24708769

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

PubMed Central

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

Preparative Production of Acetylcholinesterase and Paraoxonase in Procaryotic and Eucaryotic Expression in Systems

DTIC Science & Technology

2006-01-01

HDL, ’good cholesterol ’) and are involved in the prevention of atherosclerosis . We describe the first crystal structure of a PON family member, a... atherosclerosis and to OP poisoning3. In vitro assays show that PON1 and PON3 inhibit lipid oxidation in LDL (“bad cholesterol ”), thus reducing levels of...PON3, which share ~60% sequence identity with PON1. PON1 and PON3 reside in the cholesterol -carrying HDL (“good cholesterol ”) particles, whereas

Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model

USDA-ARS?s Scientific Manuscript database

Cholestyramine(CA)is a bile acid sequestrant widely used as a cholesterol-lowering drug to treat hypercholesterolemia, one of the major risk factors for cardiovascular disease. Despite the wide use of CA its effect on cholesterol and lipid metabolism at a molecular level and over the long term remai...

Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

PubMed

Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

1995-02-01

Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (< .5 mg/kg). Feeding copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

Associations between eating competence and cardiovascular disease biomarkers.

PubMed

Psota, Tricia L; Lohse, Barbara; West, Sheila G

2007-01-01

Explore the relationship between eating competence (EC) and biomarkers of risk for cardiovascular disease (CVD). Secondary analysis of data collected for a larger, 2-way crossover clinical trial. Outpatient clinical research center. Forty-eight hypercholesterolemic (LDL cholesterol > or = 110 mg/dL) men (n = 19) and women (n = 29) 21 to 70 years of age. Participant descriptives, cardiovascular disease biomarker levels, and eating competence (EC) determined by the ecSatter Inventory (ecSI). T tests for differences in eating competence between males and females, analysis of variance for differences in risk between those categorized as EC or not. Associations between EC and baseline biochemical measures, as well as participant characteristics and dietary intake, were assessed by Pearson correlation analyses. Logistic regression estimated relative risk of CVD risk factors from ecSI scores. Several significant associations were found between EC total and CVD risk factors. Eating competence was positively correlated with HDL-cholesterol, and inversely associated with systolic and diastolic blood pressure. High EC participants had significantly lower ratios of total cholesterol: HDL-cholesterol and triglycerides: HDL-cholesterol. Participants who were not eating competent were 5 times more likely to have LDL-cholesterol levels > or =130 mg/dL and 7 times more likely to have triglyceride levels > or =150 mg/dL. Eating competence appears to be a cognitive, affective construct with physiological manifestations, making nutrition education to increase eating competence a medical nutrition therapy.

Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction.

PubMed

Zimetti, Francesca; De Vuono, Stefano; Gomaraschi, Monica; Adorni, Maria Pia; Favari, Elda; Ronda, Nicoletta; Ricci, Maria Anastasia; Veglia, Fabrizio; Calabresi, Laura; Lupattelli, Graziana

2017-10-01

Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition, and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes, or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44.8%, respectively) and of medium-sized HDL (-10.5%) occurred in APR. Total HDL CEC was impaired in APR subjects (-18%). Evaluating specific CEC pathways, we found significant reductions in CEC by aqueous diffusion and by the transporters scavenger receptor B-I and ABCG1 (-25.5, -41.1 and -30.4%, respectively). ABCA1-mediated CEC was not affected. Analyses adjusted for age and gender provided similar results. In addition, correcting for HDL-cholesterol (HDL-C) levels, the differences in aqueous diffusion total and ABCG1-CEC remained significant. APR subjects displayed higher levels of HDL serum amyloid A (+20-folds; P = 0.003). In conclusion, APR does not associate with cholesterol synthesis and absorption changes but with alterations of HDL composition and a marked impairment of HDL CEC, partly independent of HDL-C serum level reduction. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Ezetimibe ameliorates intestinal chylomicron overproduction and improves glucose tolerance in a diet-induced hamster model of insulin resistance

PubMed Central

Naples, Mark; Baker, Chris; Lino, Marsel; Iqbal, Jahangir; Hussain, M. Mahmood

2012-01-01

Ezetimibe is a cholesterol uptake inhibitor that targets the Niemann-Pick C1-like 1 cholesterol transporter. Ezetimibe treatment has been shown to cause significant decreases in plasma cholesterol levels in patients with hypercholesterolemia and familial hypercholesterolemia. A recent study in humans has shown that ezetimibe can decrease the release of atherogenic postprandial intestinal lipoproteins. In the present study, we evaluated the mechanisms by which ezetimibe treatment can lower postprandial apoB48-containing chylomicron particles, using a hyperlipidemic and insulin-resistant hamster model fed a diet rich in fructose and fat (the FF diet) and fructose, fat, and cholesterol (the FFC diet). Male Syrian Golden hamsters were fed either chow or the FF or FFC diet ± ezetimibe for 2 wk. After 2 wk, chylomicron production was assessed following intravenous triton infusion. Tissues were then collected and analyzed for protein and mRNA content. FFC-fed hamsters treated with ezetimibe showed improved glucose tolerance, decreased fasting insulin levels, and markedly reduced circulating levels of TG and cholesterol in both the LDL and VLDL fractions. Examination of triglyceride (TG)-rich lipoprotein (TRL) fractions showed that ezetimibe treatment reduced postprandial cholesterol content in TRL lipoproteins as well as reducing apoB48 content. Although ezetimibe did not decrease TRL-TG levels in FFC hamsters, ezetimibe treatment in FF hamsters resulted in decreases in TRL-TG. Jejunal apoB48 protein expression was lower in ezetimibe-treated hamsters. Reductions in jejunal protein levels of scavenger receptor type B-1 (SRB-1) and fatty acid transport protein 4 were also observed. In addition, ezetimibe-treated hamsters showed significantly lower jejunal mRNA expression of a number of genes involved in lipid synthesis and transport, including srebp-1c, sr-b1, ppar-γ, and abcg1. These data suggest that treatment with ezetimibe not only inhibits cholesterol uptake, but may also alter intestinal function to promote improved handling of dietary lipids and reduced chylomicron production. These, in turn, promote decreases in fasting and postprandial lipid levels and improvements in glucose homeostasis. PMID:22345552

Dyslipidaemia and its treatment in patients with type 2 diabetes: A joint analysis of the German DIVE and DPV registries.

PubMed

Bramlage, Peter; Lanzinger, Stefanie; Rathmann, Wolfgang; Gillessen, Anton; Scheper, Nikolaus; Schmid, Sebastian M; Kaltheuner, Matthias; Seufert, Jochen; Danne, Thomas; Holl, Reinhard W

2016-09-04

To compare lipid abnormalities in people with and without type 2 diabetes mellitus (T2DM) and to assess the effect of treatment. We combined data from the German DIVE (DIabetes Versorgungs-Evaluation) and DPV (Diabetes-Patienten-Verlaufsdokumentation) databases to produce a large cohort of people with T2DM. The characteristics of people receiving and not receiving lipid-modifying therapy (LMT) were compared, including demographics, cardiovascular (CV) risk factors and comorbidities. Lipid profiles were evaluated, and the achievement of recommended LDL cholesterol and non-HDL cholesterol targets was assessed. The effect on lipid levels in subgroups of patients aged ≥60 years, being obese or with CV disease was also investigated. A total of 363 949 people were included in the analysis. Of these, only 97 160 (26.7%) were receiving LMT. These individuals were older than those not receiving LMT, and comorbidities were more prevalent. Statins were the most commonly used agents (84.2%), with ezetimibe, fibrates and nicotinic acid taken by a small proportion of people. The median LDL cholesterol level was lower for the LMT group (100.5 vs 114.0 mg/dL; P < .001), as was the non-HDL cholesterol level (131.0 vs 143.1 mg/dL; P < .001), while the triglyceride level was higher (160.3 vs 152.0 mg/dL; P < .001). HDL cholesterol was lower in the LMT group for both men (41.0 vs 42.0 mg/dL; P < .001) and women (47.5 vs 48.0 mg/dL; P < .001). Elderly people were more likely to have achieved the target lipid levels, while obese people were less likely. For people with CV disease, there was a greater likelihood of achieving LDL, total and non-HDL cholesterol targets, but less chance of attaining a desired HDL cholesterol level. Dyslipidaemia was highly prevalent in this large population and management of lipid abnormalities was suboptimal. The distinct lipid profile of people with T2DM warrants further investigation into the use of non-statins in addition to statin LMT. © 2016 John Wiley & Sons Ltd.

Isolated soya protein with standardised levels of isoflavones, cotyledon soya fibres and soya phospholipids improves plasma lipids in hypercholesterolaemia: a double-blind, placebo-controlled trial of a yoghurt formulation.

PubMed

Puska, Pekka; Korpelainen, Vesa; Høie, Lars H; Skovlund, Eva; Smerud, Knut T

2004-03-01

The objective was to study whether a yoghurt containing isolated soya protein with standardised levels of isoflavones, cotyledon soya fibres and soya phospholipids is more effective in lowering total and LDL-cholesterol than a placebo. One hundred and forty-three subjects were randomised to the soya group (n 69) or to the placebo (n 74). The mean baseline levels were 7.6 and 5.1 mmol/l for total and LDL-cholesterol, respectively. Fasting serum lipoproteins were assessed five times during the 8-week intervention period, and 4 weeks thereafter. The results were analysed by a mixed model for unbalanced repeated measurements. During the intervention, there were highly significant differences in lipid-lowering effect in favour of the active soya intervention group compared with the control group. The significant differences were for total cholesterol (estimated mean difference 0.40 mmol/l; P<0.001), LDL-cholesterol (0.39 mmol/l; P<0.001), non-HDL-cholesterol (0.40 mmol/l; P<0.001) and for the total:HDL-cholesterol ratio (0.23; P=0.005). There was no difference in the effects on HDL-cholesterol, triacylglycerols or homocysteine. The lipid-lowering effect occurred within 1-2 weeks of intervention, and was not due to weight loss. The safety profile for active soya was similar to the placebo group, except for gastrointestinal symptoms, which caused a significantly higher dropout rate (fourteen v. three subjects) among the subjects taking active soya.