Cholesterol Acyltransferase Activity Research Articles

Impaired HDL function and endothelial barrier stability in severe anaphylaxis

Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins (Apo) A1 and B in serum from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient serum, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Lastly, the effect of anaphylactic-derived HDL particles on the endothelial barrier was studied. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. Severe anaphylactic reactions show statistically significant low levels of HDL-C, LDL-C, ApoA1, and ApoB, which points to a possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human sera-cell assays, we observed an impaired capacity of ApoB-depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies.

Cholesterol esterification is hampered in alzheimer’s disease and cholesteryl esters composition is consequently altered

Introduction and Aim: Several epidemiological studies indicate a strong inverse association between the risk of developing Alzheimer’s disease (AD) and plasma HDL-C levels. The mechanism by which plasma HDL influence the pathogenesis and progression of AD is still unsolved and since cholesterol esterification is a crucial step in HDL metabolism it could be involved. The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s Disease (AD) patients. Methods: The study enrolled 70 AD patients and 74 cognitively-normal controls comparable for age and sex. Lipids and lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF using assays set for measurement in plasma, which were appropriately modified for CSF. Results: AD patients have normal plasma lipids, but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls, but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ1-42 CSF content. Conclusions: Taken together data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients, and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42).

Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity

BackgroundAbdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. ObjectivesOur aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. MethodsSeventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. ResultsThe obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). ConclusionsChildren and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.

Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease

ObjectiveThe purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients.MethodsThe study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF.ResultsAD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ1-42 CSF content.ConclusionTaken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42).

A High Cholesterol, (n-3) Polyunsaturated Fatty Acid Diet Induces Hypercholesterolemia More than a High Cholesterol, (n-6) Polyunsaturated Fatty Acid Diet in Hamsters

This study was designed to study the effects of (n-3) polyunsaturated fatty acids (PUFA) on plasma and liver lipids, particularly lipoprotein cholesterol concentrations, in hamsters. Diets rich in (n-3) PUFA (21 g/100 g fatty acid) or (n-6) PUFA (37.4 g/100 g fatty acid) with or without 5 g/kg cholesterol (C) supplements were given for 4 wk to male hamsters weighing 70–90 g. The VLDL- and (IDL + LDL)-cholesterol concentrations were 114 and 128% higher in hamsters fed the (n-3) PUFA + C diet than in those fed the (n-6) PUFA + C diet. However, these differences were not observed when cholesterol was not supplemented. Hamsters fed the (n-3) PUFA diet had significantly lower plasma and hepatic triglyceride concentrations were comparable in hamsters fed (n-6) PUFA + C and (n-3) PUFA + C. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-CoA:cholesterol acyltransferase activity and VLDL cholesteryl esters were significantly higher in hamsters fed the (n-3) PUFA + C diet than in those fed the (n-6) PUFA + C diet. Our results demonstrate that elevation of VLDL- and (IDL + LDL)-cholesterol in hamsters by (n-3) PUFA, compared with (n-6) PUFA, is dependent on dietary cholesterol supplementation and may be due to decreased catabolism of these lipoproteins.

Obesity Affects Maternal and Neonatal HDL Metabolism and Function.

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m2) and women with normal weight (prepregnancy BMI < 25 kg/m2), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin−cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring.

Abstract 11397: Circulating Human Metabolites Resulting From TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Hypocholesterolemic Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons From an Original ex vivo Clinical Trial

Introduction: TOTUM-070 is a patented polyphenol-rich compound which has shown hypocholesterolemic properties in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the metabolites produced by the digestive tract following the ingestion of TOTUM-070 in humans. Methods: Human serum was collected in healthy subjects before and following acute intake of 5g of TOTUM-070. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-070 absorption was further incubated with human hepatocytes, pretreated or not with palmitate (250 μM). In such lipotoxic environment, hepatocyte behavior was monitored to determine whether and how TOTUM-070 metabolites may improve cholesterol metabolism in human. Results: In the presence of the human metabolites from TOTUM-070, human hepatocytes were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. Hepatocyte protection was characterized by (1) the inhibition of both triglycerides (-41%, p&lt;0.001) and cholesterol (-50%, p&lt;0.001) storage, (2) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity reduced by 44%, p&lt;0.001), (3) a lowered fatty acid synthase expression (p&lt;0.001), (4) the stimulation of the Lecithin Cholesterol Acyl Transferase (LCAT) activity (p&lt;0.05) and finally (5) a higher CYP7A1 expression (p&lt;0.05). All together, these data provide new biochemical insights into the mechanisms underlying, in humans, the beneficial impact of TOTUM-070 on lipid metabolism in liver cells. Conclusion: Using a pioneering clinical ex vivo approach considering the digestive processes of nutrients, we give clues on the role of circulating metabolites produced following TOTUM-070 intake in humans in hepatocyte protection.

Lycopene-rich diets modulate HDL functionality and associated inflammatory markers without affecting lipoprotein size and distribution in moderately overweight, disease-free, middle-aged adults: A randomized controlled trial.

BackgroundThe consumption of lycopene-rich foods may lower cardiovascular disease (CVD) risk. Lycopene circulates in the blood bound to lipoproteins, including high-density lipoproteins (HDLs). Preliminary data from our group showed that increased consumption of tomato-based food or lycopene supplement in middle-aged subjects led to functional changes to HDL's sub-fractions, HDL2 and HDL3. These changes were also associated with a decrease in serum amyloid A (SAA), potentially enhancing their anti-atherogenic properties.ObjectiveWe carried out a comprehensive randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods or lycopene supplements affects HDL functionality and associated inflammatory markers, and lipoprotein subfractions size and distribution.DesignVolunteers (225, aged 40–65 years) were randomly assigned to one of three dietary intervention groups and asked to consume a control diet (low in tomato-based foods, <10 mg lycopene/week), a lycopene-rich diet (224–350 mg lycopene/week), or the control diet with a lycopene supplement (70 mg lycopene/week). HDL2 and HDL3 were isolated by ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum. Systemic and HDL-associated inflammation was assessed by measuring SAA concentrations. HDL functionality was determined by monitoring paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin cholesterol acyltransferase (LCAT) activities. The lipoprotein subfractions profile was assessed by NMR.ResultsLycopene in serum and HDL significantly increased following consumption of both the high tomato diet and lycopene supplement (p ≤ 0.001 for both). Lycopene, either as a tomato-rich food or a supplement, enhanced both serum- and HDL3-PON-1 activities (p ≤ 0.001 and p = 0.036, respectively), while significantly reducing HDL3-SAA-related inflammation (p = 0.001). Lycopene supplement also significantly increased HDL3-LCAT activity (p = 0.05), and reduced the activity of both HDL2- and HDL3-CETP (p = 0.005 and p = 0.002, respectively). These changes were not associated with changes in the subclasses distribution for all lipoprotein fractions or the size of lipoprotein subclasses.ConclusionOur results showed that dietary lycopene can significantly enhance HDL functionality, without associated changes in particle size and distribution, by modulating the activity of HDL-associated enzymes. Concomitantly, dietary lycopene significantly decreased serum- and HDL3-associated SAA, confirming that SAA may represent a sensitive inflammatory biomarker to dietary change.Clinical Trial Register(https://www.isrctn.com), ISRCTN34203810.

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.

Measures of high-density lipoprotein function in men and women with severe aortic stenosis

BackgroundCalcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear.MethodsUsing cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC).ResultsHDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-β1 and α-particles were higher in woman than in men by spectral density, (pre-β1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03).ConclusionsSex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS.Graphical abstractSex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preβ-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.

Bioactive components to inhibit foam cell formation in atherosclerosis.

The production of lipid-laden cells in macrophages after significant ingestion of oxidized low-density lipoprotein is considered the most critical phase in the creation of atherosclerotic lesions, which is known as foam cell formation. Targeting foam cell development to find a potential therapeutic strategy for the management of atherosclerosis has yielded numerous promising outcomes. Multiple variables influence foam cell growth, including scavenger receptor expression, cholesterol transporter expression acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity. Plants used during herbal therapy have been shown to assist with a variety of ailments. In this study, we found medicinal plants and their bioactive components suppress foam cell formation in a variety of ways; some inhibit cholesterol transporter and lectin-like oxidized low-density lipoprotein receptor-1 upregulation, while others inhibit the function of acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity. Recent study findings related to the synthesis of the new active component from plant sources by focusing on the typical process involved in the generation of foam cells. We're also looking at using a cellular target-based therapeutic approach to generate novel plant-based medications for the cure of atherosclerosis.

Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Herein, Tyr192 in apoA-I was found to be the major chlorination site in both lesion and plasma HDL from humans with atherosclerosis, while MPO binding to apoA-I was demonstrated by immunoprecipitation studies in vivo. In vitro, MPO-mediated damage of lipid-free apoA-I impaired its ability to promote cellular cholesterol efflux by the ABCA1 pathway, whereas oxidation to lipid-associated apoA-I inhibited lecithin:cholesterol acyltransferase activation, two key steps in reverse cholesterol transport. Compared with native apoA-I, apoA-I containing a Tyr192 → Phe mutation was moderately resistant to oxidative inactivation by MPO. In high-fat-diet-fed apolipoprotein E-deficient mice, compared with native apoA-I, subcutaneous injection with oxidized apoA-I (MPO treated) failed to mediate the lipid content in aortic plaques while mutant apoA-I (Tyr192 → Phe) showed a slightly stronger ability to reduce the lipid content in vivo. Our observations suggest that oxidative damage of apoA-I and HDL involves MPO-dependent site-specific tyrosine chlorination, raising the feasibility of producing MPO-resistant forms of apoA-I that have stronger antiatherosclerotic activity in vivo.

Evaluation of lipid metabolizing enzymes: Paraxonase1 (PON1) and lecithin cholesterol acyltransferase (LCAT) activities in children with nephrotic syndrome

Background: The most common glomerular disorder in children is nephrotic syndrome, associated with high morbidity despite notable advances in its treatment. Many of the nephrotic syndrome complications, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidemia. Paraoxonase enzyme is responsible for the most of the antioxidant properties of HDL, thus preventing the formation of atherogenic ox-LDL molecules, and lecithin cholesterol acyltransferase is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport pathway, which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Objectives: The present study aimed to investigate the serum activities of paraoxonase-1 (PON-1) and lecithin cholesterol acyltransferase (LCAT) in children with nephrotic syndrome in an active phase (as newly diagnosed or old cases with acute relapse). Also, to study any correlation exists between paraoxonase-1 activity and lipid profile. Methods: This study consists of group 1 with 40 cases of nephrotic syndrome in the age group of (2-14 years) and group 2 with 40 age and sex-matched healthy controls. Lipid profile and paraoxonase activity, lecithin cholesterol acyltransferase activities were measured in both groups’ serum samples. Results: Statistical analysis of student’s t-test showed that the mean levels of total cholesterol, triglycerides, LDL were significantly increased in group 1 when compared to Group 2 (p &lt;0.001). PON1 and lecithin cholesterol acyltransferase levels were significantly lower in group 1 compared to group 2, and there is no significant difference among nephrotic groups. Conclusions: Both paraoxonase-1 enzyme and lecithin cholesterol acyltransferase are considered good promising predictors for nephrotic syndrome and other parameters such as LDL, HDL, and TG. The significantly decreased paraoxonase-1 enzyme and lecithin cholesterol acyltransferase activities result in increased oxidation of LDL, thus accelerating atherosclerosis.

Beneficial Effects of Algerian Green Alga Ulva lactuca and Its Hydroethanolic Extract on Insulin Resistance and Cholesterol Reverse Transport in High-Fat/Streptozotocin Diabetic Rats

The aim of this study was to evaluate the impact of the green algae Ulva lactuca and its hydroethanolic extract on insulin resistance and cholesterol reverse transport in type 2 diabetic (T2D) rats. Rats had T2D induced by a high-fat diet (HFD) for 5 weeks followed by intraperitoneal injection of streptozotocin. Diabetic rats were divided into three groups and were fed a HFD in the presence or absence of 1% alga (HFD-Alg) or 1% of its hydroethanolic extract (HFD-Ext), for 4 weeks. The control group consumed 20% casein combined with 5% lipids. Hyperglycemia, insulin resistance, hypercholesterolemia, and hypertriglyceridemia were noted in HFD rats vs control rats. Whole alga and its extract decreased these parameters vs the HFD. Moreover, fecal total cholesterol and triacylglycerols levels were lowered in HFD group vs C group, but were increased with HFD-Alg vs HFD. Compared with the Control, the HFD group had decreased lecithin:cholesterol acyltransferase (LCAT) activity, apolipoprotein A-I (ApoA-I), high-density lipoprotein (HDL3)-phospholipids (PL), and HDL2-cholesteryl ester (CE) levels, but increased HDL3-unesterified cholesterol (UC) levels. Furthermore, compared with the HFD group, the HFD-Alg and HFD-Ext groups had increased LCAT activity, ApoA-I, HDL3-PL, and HDL2-CE levels and decreased HDL3-UC levels. In addition, in the HFD-Ext group, LCAT activity and ApoA-1 levels were decreased vs the HFD-Alg whereas HDL3-UC levels were increased. In conclusion, these results indicate that U. lactuca and its hydroethanolic extract have curative effect on T2D. Therefore, this alga could be considered a functional food supplement for the treatment and prevention of diabetes.

Association entre le comportement alimentaire et les biomarqueurs cardiométaboliques chez des femmes ménopausées de l’ouest algérien ​

Background: Abdominal adiposity, insulin resistance dyslipidemia, and endothelial dysfunction emerge during menopause. Objectives: To assess the relationship between lifestyle, eating behavior, and cardiometabolic biomarkers in Algerian postmenopausal women. Subjects and Methods: A prospective cross-sectional survey was conducted among 228 postmenopausal women (57.65±6.42 years) in Oran (Algeria). Women were divided into quartiles according to their waist circumference (WC); Q1 (69-89cm), Q2 (90-98.5cm), Q3 (99-108cm), and Q4 (108-125cm). We assessed for 3 days, food consumption by the 24h recall and record method, and daily energy expenditure (DEE). In serum, we analyzed the lipid profile, inflammation markers, and oxidative status. Results: DEE and total energy intake were similar in all groups. A decrease in metabolism equivalent tasks (Mets) was observed according to WC increase (&lt;1.5). The Mets was negatively correlated with LDL-cholesterol, triacylglycerols (TG), lipid accumulation products (LAP), CRP, thiobarbituric acid reactive substances (TBARS), TBARS-LDL, and carbonyls and positively correlated with the activity of lecithin cholesterol acyltransferase (LCAT), superoxide dismutase (SOD) and catalase. An inverse relationship was noted between the intake of meats, poultry, eggs, fish, and antioxidant enzymatic activities. Fat intake was positively correlated with lipid accumulation products (r=0.293, p&lt;0.001) and negatively with HDL-cholesterol (r=-0.396, p&lt;0.001), LCAT activity (r= -0.275, p&lt;0.001) and C-Reactive Protein (CRP) (r= -0.315, p&lt;0.001). Fruits and vegetables intake was negatively correlated with LDL-Cholesterol (r=- 0.279, p&lt;0.001) and LDL-TBARS (r= -0.284, p&lt;0.001). Conclusion: Unhealthy diet and sedentary lifestyle were associated with high cardiometabolic risk factors in postmenopausal women and exposed them to cardiovascular diseases. Keywords: Lifestyle behavior, Cardiometabolic biomarkers, Waist circumference, Postmenopausal women.

Association entre le comportement alimentaire et les biomarqueurs cardiométaboliques chez des femmes ménopausées de l’ouest algérien

Background: Abdominal adiposity, insulin resistance dyslipidemia, and endothelial dysfunction emerge during menopause. Objectives: To assess the relationship between lifestyle, eating behavior, and cardiometabolic biomarkers in Algerian postmenopausal women. Subjects and Methods: A prospective cross-sectional survey was conducted among 228 postmenopausal women (57.65±6.42 years) in Oran (Algeria). Women were divided into quartiles according to their waist circumference (WC); Q1 (69-89cm), Q2 (90-98.5cm), Q3 (99-108cm), and Q4 (108-125cm). We assessed for 3 days, food consumption by the 24h recall and record method, and daily energy expenditure (DEE). In serum, we analyzed the lipid profile, inflammation markers, and oxidative status. Results: DEE and total energy intake were similar in all groups. A decrease in metabolism equivalent tasks (Mets) was observed according to WC increase (&lt;1.5). The Mets was negatively correlated with LDL-cholesterol, triacylglycerols (TG), lipid accumulation products (LAP), CRP, thiobarbituric acid reactive substances (TBARS), TBARS-LDL, and carbonyls and positively correlated with the activity of lecithin cholesterol acyltransferase (LCAT), superoxide dismutase (SOD) and catalase. An inverse relationship was noted between the intake of meats, poultry, eggs, fish, and antioxidant enzymatic activities. Fat intake was positively correlated with lipid accumulation products (r=0.293, p&lt;0.001) and negatively with HDL-cholesterol (r=-0.396, p&lt;0.001), LCAT activity (r= -0.275, p&lt;0.001) and C-Reactive Protein (CRP) (r= -0.315, p&lt;0.001). Fruits and vegetables intake was negatively correlated with LDL-Cholesterol (r=- 0.279, p&lt;0.001) and LDL-TBARS (r= -0.284, p&lt;0.001). Conclusion: Unhealthy diet and sedentary lifestyle were associated with high cardiometabolic risk factors in postmenopausal women and exposed them to cardiovascular diseases. Keywords: Lifestyle behavior, Cardiometabolic biomarkers, Waist circumference, Postmenopausal women.

Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study

BackgroundWe hypothesized that the addition of eicosapentaenoic acid (EPA) to ongoing statin therapy could change the particle heterogeneity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles, even in stable coronary artery disease (CAD) patients. MethodsWe assigned CAD patients already receiving statin therapy to one of two groups: an EPA group (1800 mg/day; n = 30) and a control group (n = 30). A gel permeation high-performance liquid chromatography method was used to measure the particle concentration and number of lipoprotein subclasses. ResultsIn the EPA group, significant decreases of both the concentration and number of medium LDL (p = 0.0002 and 0.0001), small LDL (p = 0.0004 and 0.0005) and very small LDL (p = 0.0005 and 0.002) particles were observed. Conversely, the concentration and number of large HDL particles increased significantly (p = 0.024 and 0.048). The concentration of very large HDL particles also increased significantly (p = 0.028). Furthermore, significant correlations between the variables that showed significant changes in the LDL and HDL particle subclasses, and the EPA/arachidonic acid (AA) ratio were found. No other significant associations of lipoprotein particle heterogeneity with the serum EPA/AA ratio were noted in either the control group or the EPA group. Interestingly, univariate and multivariate regression analyses revealed that increased serum lecithin–cholesterol acyltransferase activity, a key enzyme of HDL cholesterol efflux, was a predictor for increased above-mentioned HDL particles subclasses. ConclusionsAdministration of EPA might alter both LDL and HDL particle heterogeneity, causing decreased concentration and number of smaller LDL particles and increased concentration and number of larger HDL particles. Furthermore, addition of EPA to ongoing statin therapy appears to be capable of increasing the EPA/AA ratio, which might have an anti-atherosclerotic effect on lipoprotein particle heterogeneity, even in stable CAD patients with well-controlled serum lipid levels. Clinical Trial RegistrationUMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.

Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration: a proof of concept.

Glucocorticoids (GC) are associated with increased cardiovascular morbidity despite increased HDL-C concentration. HDL-mediated cholesterol efflux, a major anti-atherogenic property of HDL particles, is negatively associated with CVD risk. We aimed to determine whether HDL-mediated cholesterol efflux was influenced by GC. Prospective, observational study. Lipid parameters, HDL composition, HDL-mediated cholesterol efflux, cholesteryl ester transfer protein, phospholipid transfer protein and lecithin cholesterol acyl-transferase (LCAT) activities were determined in ten patients with giant cell arteritis before and 3 months after GC introduction and in seven control subjects. HDL concentration and composition, HDL-mediated cholesterol efflux and LCAT activity were determined in GC-treated mice. In patients, HDL-C concentration was higher after than before treatment GC-treatment (P = 0.002), while HDL-mediated cholesterol efflux was decreased (P = 0.008) and negatively associated with the proportion of cholesteryl ester in HDL (P = 0.04), independently of CRP. As well, in mice, HDL-C level was increased after GC exposure (P = 0.04) and HDL-mediated cholesterol efflux decreased (P = 0.04). GC-treated patients had higher cholesteryl ester content in HDL, higher HDL2-to-HDL3 ratio and higher LCAT activity than before treatment (P = 0.008, P = 0.02 and P = 0.004, respectively). We report, for the first time, that in patients with giant cell arteritis and mice treated with GC, HDL-mediated cholesterol efflux was impaired by GC besides an increased HDL-C level. This impaired HDL functionality, possibly related to HDL enrichment in cholesteryl ester, could contribute to the increased CVD risk observed in GC-treated patients. Further studies are needed in larger populations, to further decipher the effect of GC on HDL.

Antihypercholesterolemic and anti-atherogenic effects of lyophilized aqueous extract of Globularia alypum leaves in rats fed a high-cholesterol diet

PurposeThis paper aims to investigate the preventive effects of a concomitant supplementation of a lyophilized aqueous extract of Globularia alypum (Ga) leaves in a high cholesterol-diet (HC-D) on lipid profile and lecithin cholesterol acyltransferase (LCAT) activity in hypercholesterolemic rats.Design/methodology/approachTwenty-four male Wistar rats weighing 232 ± 10 g were divided into four groups (n = 6). Two control groups were fed a standard-diet (St-D) supplemented (C-Ga) or not (C) with 1.66% Ga leaf extract. The two others experimental groups were fed HC-D, which contains the St-D plus 1% of cholesterol and 0.5% of cholic acid supplemented (HC-Ga) or not (HC) with the same amount of Ga. At d28, feces were collected and fasting rats were anesthetized; bloods and livers were removed to measure biochemical parameters.FindingsIn hypercholesterolemic (HC) rats, Ga supplementation in HC-D induced a significant reduction in ALT (−64%, p = 0.002) and AST (−71%; p = 0.005) activities, in plasma TC (−55%; p = 0.03) and TG (−54%; p = 0.01) concentrations, in cholesterol contents of atherogenic lipoproteins VLDL (−78%; p = 0.004) and LDL-HDL1 (−64%; p = 0.003) and inversely, an increase in those of anti-atherogenic HDL2 (+14%; p = 0.002). Feeding the HC-D-Ga exhibited a reduction in atherogenic index Apo B/Apo A-I (−72%; p = 0.002), an increase in faecal lipids, cholesterol excretion and in plasma apo A-I (+60%; p = 0.002) and HDL2-cholesteryl esters (+32%, p = 0.04) and then improved LCAT activity (+31%; p = 0.03).Originality/valueIn hypercholesterolemic rats, Globularia alypum extract was effective in preventing lipid disorders by its hypolipidemic action, had an anti-atherogenic potential and a protective effect against cardiovascular risk by enhancing LCAT activity.

ApoE and apoC-III-defined HDL subtypes: a descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity

BackgroundThe functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans.MethodsEighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting.ResultsHDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = − 0.55, P = 0.017) and E-C- alpha 1 HDL (r = − 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025).ConclusionsThe presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.