HDL Diameter Research Articles

Abstract MP28: Advanced Lipid Status Parameters in Women With Preeclampsia

Preeclampsia (PE) is a hypertensive disorder associated with pregnancy, usually occurring after the 20th week of gestation, followed by proteinuria or signs of end-organ dysfunction. Early-onset preeclampsia is associated with placental dysfunction, while late-onset preeclampsia is recognized as a maternal disorder, influenced by risk factors like maternal obesity, diabetes mellitus, or chronic hypertension. During physiological pregnancy, lipid metabolism changes to adequately supply the fetoplacental unit with nutrients and energy, consequently changing the composition of LDL and HDL particles. However, in preeclampsia, these changes become atherogenic. The study aimed to examine changes in advanced lipid status parameter concentrations and the dominant diameter of LDL and HDL particles during pregnancies affected by PE. In this study, 92 pregnant women at high risk for complication development were followed longitudinally throughout the first (T1), second (T2), and third (T3) trimesters. They were classified into high-risk (HR) (72 women) and PE (20 women) groups based on pregnancy outcomes. Total cholesterol (TC), HDL-C, triglycerides (TG), apoAI, and apoB concentrations were measured using commercial kits, while LDL-C concentrations and the atherogenic index of plasma (AIP) were calculated using established equations. Dominant LDL and HDL particle sizes were determined by gradient gel electrophoresis. TG levels were significantly higher in the PE group compared to the HR group across all trimesters (p<0.05; p<0.05; p<0.01), while AIP was significantly elevated in T2 (p<0.01) and T3 (p<0.01). HDL-C levels were lower in the PE group than in the HR group in T2 (p<0.05). In the HR group during pregnancy, concentrations of TC, TG, LDL-C, apoB, as well as HDL-C increased significantly (p<0.05 for all parameters), while the dominant LDL diameter decreased markedly (p<0.001) between all trimesters, without changes in the dominant HDL diameter. There were no changes in HDL-C concentration during pregnancy in the PE group. In contrast, TG concentrations increased significantly (p<0.01), accompanied by a significant decrease in dominant LDL particle diameter (p<0.05). In conclusion, pregnant women with PE exhibit atherogenic changes in lipid status parameters, including no increase in HDL-C concentration, potentially leading to a loss of HDL's protective effect.

Cholesterol transfer to high‐density lipoprotein in obesity and the effects of weight loss after bariatric surgery

SummaryObesity increases serum triglycerides and decreases high‐density lipoprotein cholesterol (HDL‐C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1‐OB) and III (G3‐OB) obesity and effects of bariatric surgery on G3‐OB. Fifteen G3‐OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1‐OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3‐OB had higher triglycerides and lower HDL‐C; G1‐OB had higher triglycerides than NW but HDL‐C was equal. Compared to NW, HDL size was smaller in G3‐OB but equal in G1‐OB. One year after bariatric surgery, BMI and triglycerides of G3‐OB decreased (p < .0001 and p = .0012, respectively) and HDL‐C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3‐OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL‐C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.

Altered Distribution of Unesterified Cholesterol among Lipoprotein Subfractions of Patients with Diabetes Mellitus Type 2.

Biomarkers are important tools to improve the early detection of patients at high risk for developing diabetes as well as the stratification of diabetic patients towards risks of complications. In addition to clinical variables, we analyzed 155 metabolic parameters in plasma samples of 51 healthy volunteers and 66 patients with diabetes using nuclear magnetic resonance (NMR) spectrometry. Upon elastic net analysis with lasso regression, we confirmed the independent associations of diabetes with branched-chain amino acids and lactate (both positive) as well as linoleic acid in plasma and HDL diameter (both inverse). In addition, we found the presence of diabetes independently associated with lower concentrations of free cholesterol in plasma but higher concentrations of free cholesterol in small HDL. Compared to plasmas of non-diabetic controls, plasmas of diabetic subjects contained lower absolute and relative concentrations of free cholesterol in all LDL and HDL subclasses except small HDL but higher absolute and relative concentrations of free cholesterol in all VLDL subclasses (except very small VLDL). These disbalances may reflect disturbances in the transfer of free cholesterol from VLDL to HDL during lipolysis and in the transfer of cell-derived cholesterol from small HDL via larger HDL to LDL.

PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses

BackgroundMedications leveraging the leptin, PCSK9, ANGPTL3 and FABP4 pathways are being developed for the treatment of insulin resistance and/or lipid disorders. To evaluate whether these pathways are independent from each other, we assessed the levels of PCSK9, ANGPTL3 and FABP4, in normal subjects and subjects exhibiting HIV and highly active antiretroviral therapy (HAART) induced metabolic syndrome with lipoatrophy and hypoleptinemia. Studies were performed at baseline and during food deprivation for three days with either a placebo or leptin administration at physiological replacement doses to correct fasting induced acute hypoleptinemia and in pharmacological doses. MethodsPCSK9, ANGPTL3, FABP4 levels and their correlations to lipoproteins-metabolites were assessed in randomized placebo controlled cross-over studies: a) in 15 normal-weight individuals undergoing three-day admissions in the fed state, in complete fasting with placebo and in complete fasting with leptin treatment in physiologic replacement doses (study 1), b) in 15 individuals day baseline in a fed and three fasting admissions for three days with leptin administered in physiologic, supraphysiologic and pharmacologic doses (study 2), c) in 7 hypoleptinemic men with HIV and HAART-induced lipoatrophy treated with leptin or placebo for two months in the context of a cross over randomized trial (study 3). ResultsCirculating ANGPTL3, PCSK9 and FABP4 were markedly elevated in HIV-lipoatrophy and not affected by leptin treatment. PCSK9 levels correlated with lipids and markers of lipid utilization and lipolysis. ANGPTL3 levels correlated with HDL particles and their lipid composition. FABP4 levels were negatively associated with HDL diameter (HDL-D) and composition. PCSK9 and ANGPTL3 levels decreased during food deprivation by ~65 % and 30 % respectively. Leptin administration at physiologic, supraphysiologic and pharmacologic doses did not affect PCSK9, ANGPTL3 and FABP4 levels. ConclusionsPCSK9, ANGPTL3 and FABP4 levels are associated with markers of lipid metabolism and are higher in HIV-lipoatrophy. PCSK9 and ANGPTL3 but not FABP4 decrease in response to food deprivation. PCSK9 and ANGPTL3 regulation is leptin-independent, suggesting independent pathways for lipid regulation. Thus, combining treatments of leptin with PCSK9 and/or ANGPTL3 inhibitors for metabolic diseases should have additive effects and merit further investigation. Clinical trial informationClinicalTrials.gov no. NCT00140231, NCT00140205, NCT00140244.

Association of egg consumption, metabolic markers, and risk of cardiovascular diseases: A nested case-control study.

Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD). Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30-79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk. Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns. In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD. This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.

Influence of Gut Microbial Communities on Fasting and Postprandial Lipids and Circulating Metabolites: The PREDICT 1 Study

Abstract Objectives The human gut microbiome plays a critical role in host glucose metabolism, but its connections to other key markers of cardiometabolic health in fasting and postprandial conditions is largely unknown. The PREDICT 1 study enrolled n = 1,102 twins and unrelated healthy US/UK adults to explore the genetic, metabolic, microbial, and meal determinants of fasting metabolites and postprandial responses to foods. Methods This multi-centre dietary study assessed fasting and postprandial (0-6h) circulating metabolites over a 13d study period incorporating standardized test meals of varying nutrient composition. Shotgun metagenomics was performed from samples collected at baseline (n = 1,001 UK and 97 US). Metabolomics (NMR) was performed on clinic fasting and postprandial samples, blood glucose was continuously assessed, and blood triglycerides and C-peptide were serially measured. Results Using machine learning models, we found the fasting metabolites most strongly associated with overall gut community structure were the inflammatory marker GlycA (r = 0.31), and HDL and VLDL particle diameter (HDL-D and VLDL-D; r = 0.3 and 0.28 respectively). Variance explained was slightly greater for postprandial HDL-D and VLDL-D (at 6h; r = 0.32 and 0.31, respectively) than fasting levels, whilst the other metabolites did not differ (e.g., GlycA r = 0.28). Lipid-mediated metabolites were more closely associated with the gut microbiome in both fasting and postprandial states compared with glycemic-mediated measurements. There were distinct microbial clusters that segregated both fasting and postprandial metabolites according to their known association with cardiometabolic disease; ApoA and HDL vs. ApoB, VLDL, IDL LDL, remnant C, GlycA, IL-6, blood pressure, glucose, insulin and HbA1c. We also identified differential abundance among several microbes associated with metabolic health, including Prevotella copri and Faecalibacterium prausnitzii. Results obtained in the UK cohort were validated in the US cohort. Conclusions An individual's gut microbial composition is predictive of their cardiometabolic markers and personalized responses to food. Our data highlight the potential of the gut microbiome as a target amenable to modulation in personalized nutrition to ameliorate cardiometabolic risk. Funding Sources Zoe Global Ltd., NIHR GSTT BRC, Wellcome Trust.

Physical activity and lipidomics in a population at high risk of type 2 diabetes mellitus

ABSTRACT The aim was to investigate how measurements of the lipidome differ according to the level and intensity of physical activity in a population at high risk of type 2 diabetes (T2DM). A targeted metabolomics platform provided quantitative molecular data on lipid species. Linear regression examined the associations between plasma lipid concentrations, particle size and time spent in objectively measured physical activity intensity domains, in increments of 500 counts per minute (cpm) (up to >4500 cpm (~>5.6METs)). Results are presented as % difference in the concentration (lower/higher) or particle size (smaller/larger) per 10 min of activity within each intensity. Five hundred and nine participants were included. Time spent in the lowest physical activity intensity domain (<500 cpm) was unfavourably associated with VLDL (2%), HDL (−2%) and Apolipoprotein A-1 particle concentrations (−2%) and HDL diameter (−2%). Conversely, time spent in intensities ≥1000 cpm were favourably associated with HDL subclass concentrations; with stronger associations seen at moderate intensities (2000-3999 cpm (~4.5METs)). For Apolipoprotein-B concentration and VLDL particle concentration and size, a negative association was consistently observed at the highest physical activity intensity only. If these associations are causal, HDL subclasses appear sensitive to light-intensities whereas only the high category of physical activity intensity was consistently associated with VLDL subclasses.

Lipase C, Hepatic Type -250A/G (rs2070895) Variant Enhances Carotid Atherosclerosis in Normolipidemic and Asymptomatic Individuals from Brazil.

The common genetic variant in the promoter region of the hepatic lipase gene [LIPC -250G/A(rs2070895)] has an ambiguous association with cardiovascular disease. In this context, our study was performed to identify the relationships between the rs2070895 with carotid atherosclerosis, plasma lipids, and parameters of reverse cholesterol transport. A total of 285 normolipidemic and asymptomatic participants from an initial sample of 598,288 individuals (inclusion criteria: LDL-C ≤130 mg/dL and triglycerides ≤150 mg/dL; age: 20-75 years, both genders; confirmation of clinical, anthropometric and laboratory data; attended all visits; DNA was achieved to perform genetic analysis) were enrolled and the rs2070895 variant was genotyped by TaqMan® OpenArray® Plataform. Carotid intima-media thickness and the screening of atherosclerotic plaques were determined by B-mode ultrasonography. The rs2070895 genotype frequencies were 0.44, 0.41, and 0.15 (GG, GA, and AA, respectively). Logistic regression analysis showed that the risk of having plaques was increased in participants carrying the AA or AG genotypes (OR = 3.90; 95% CI = 1.54-10.33), despite an increase in high-density lipoprotein cholesterol levels, HDL diameter and apolipoprotein A-I, as compared to the GG genotype. Hepatic lipase and endogenous lecithin cholesterol acyl transferase activities were reduced (38% and 19%, respectively) and lipoprotein lipase was increased by 30% (AA vs GG). Our results provide evidence that the AA or AG genotypes of the rs2070895 were associated with carotid atherosclerosis in apparently healthy participants, probably as a consequence of reduced reverse cholesterol transport and accumulation of HDL subfraction 2 rich in triglycerides and depleted in cholesteryl esters that could become dysfunctional.

Metabolomic correlates of central adiposity and earlier-life body mass index

BMI is correlated with circulating metabolites, but few studies discuss other adiposity measures, and little is known about metabolomic correlates of BMI from early life. We investigated associations between different adiposity measures, BMI from childhood through adulthood, and metabolites quantified from serum using 1H NMR spectroscopy in 900 British men and women aged 60-64. We assessed BMI, waist-to-hip ratio (WHR), android-to-gynoid fat ratio (AGR), and BMI from childhood through adulthood. Linear regression with Bonferroni adjustment was performed to assess adiposity and metabolites. Of 233 metabolites, 168; 126; and 133 were associated with BMI, WHR, and AGR at age 60-64, respectively. Associations were strongest for HDL, particularly HDL particle size-e.g., there was 0.08 SD decrease in HDL diameter (95% CI: 0.07-0.10) with each unit increase in BMI. BMI-adjusted AGR or WHR were associated with 31 metabolites where there was no metabolome-wide association with BMI. We identified inverse associations between BMI at age 7 and glucose or glycoprotein at age 60-64 and relatively large LDL cholesteryl ester with postadolescent BMI gains. In summary, we identified metabolomic correlates of central adiposity and earlier-life BMI. These findings support opportunities to leverage metabolomics in early prevention of cardiovascular risk attributable to body fatness.

Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes

BackgroundDyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM. MethodsNMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry (‘baseline’, 1983–89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004–2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices. ResultsIn men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p < 0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p < 0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p < 0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women. ConclusionNMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease.

Sex-Specific Associations between Screen Time and Lipoprotein Subfractions

Time spent in sedentary activities (such as watching television) has previously been associated with several risk factors for cardiovascular disease (CVD) such as increased low-density lipoprotein cholesterol (LDL-C). Little is known about associations with lipoprotein subfractions. Using television and computer screen time in hours per day as a measure of sedentary time, we examined the association of screen time with lipoprotein subfractions. Data were used from men and women forming the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study population. Mixed linear models specified lipoprotein measures as the outcome, and screen time as the predictor for fourteen lipoprotein subfraction measures, and included age, smoking status, pedigree, and fat, carbohydrate daily alcohol and energy intake as covariates. Analyses were run separately for men (n = 623) and women (n = 671). A step-down Bonferroni correction was applied to results. The analysis was repeated for significant results (p < .05), additionally controlling for body mass index (BMI) and moderate and vigorous physical activity. Linear models indicated that screen time was associated with five lipoprotein parameters in women: the concentration of large VLDL particles (p = .01), LDL particle number (p = .01), concentration of small LDL particles (p = .04), the concentration of large HDL particles (p = .04), and HDL diameter (p = .02). All associations remained after controlling for moderate or vigorous physical activity and BMI. We show that sedentary time is associated with lipoprotein measures, markers of cardiometabolic disease, independently of physical activity and BMI, in women but not men.

A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women's Health Study

HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. (Proc Natl Acad Sci U S A 1977;74:837-41.) and compared its predictions with experimental data from the Women's Health Study (WHS). The Shen model was updated to predict the relationship between HDL diameter and the ratio of HDL-cholesterol (HDL-C) to apolipoprotein A-I (ApoA-I) plasma concentrations (HDL-C/ApoA-I ratio). In the WHS (n = 26 772), nuclear magnetic resonance spectroscopy (NMR) was used to measure the mean HDL diameter (d(mean,NMR)) and particle concentration (HDL-P); HDL-C and ApoA-I (mg/dL) were measured by standardized assays. The updated Shen model predicts a quasilinear increase of HDL diameter with the HDL-C/ApoA-I ratio, consistent with the d(mean,NMR) values from WHS, which ranged between 8.0 and 10.8 nm and correlated positively with the HDL-C/ApoA-I ratio (r = 0.608, P < 2.2 × 10(-16)). The WHS data were further described by a linear regression equation: d(WHS) = 4.66 nm + 12.31(HDL-C/Apo-I), where d(WHS) is expressed in nanometers. The validity of this equation for estimating HDL size was assessed with data from cholesteryl ester transfer protein deficiency and pharmacologic inhibition. We also illustrate how HDL-P can be estimated from the HDL size and ApoA-I concentration. This study provides a large-scale experimental examination of the updated Shen model. The results offer new insights into HDL structure, composition and remodeling and suggest that the HDL-C/ApoA-I ratio might be a readily available biomarker for estimating HDL size and HDL-P.

Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome

ObjectiveWe investigated if daily egg feeding, along with carbohydrate restriction, would alter lipoprotein metabolism and influence atherogenic lipoprotein profiles and insulin resistance in men and women with metabolic syndrome (MetS). MethodsIn a randomized, single-blind, parallel design, participants consumed either 3 whole eggs/day (EGG, n=20) or the equivalent amount of yolk-free egg substitute (SUB, n=17), as part of a moderately carbohydrate-restricted diet (25%–30% energy) for 12 weeks. Plasma lipids, apolipoproteins (apos), oxidized LDL (oxLDL), cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) activities were assessed at baseline and week 12. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. ResultsAtherogenic dyslipidemia improved for all individuals as evidenced by reductions in plasma triglycerides, apoC-III, apoE, oxLDL, VLDL particle diameter, large VDL, total IDL, small LDL, and medium LDL particles (P<0.05). Furthermore, there were increases in HDL-cholesterol, large LDL and large HDL particles (P<0.05) for all individuals. However, there were greater increases in HDL-cholesterol and large HDL particles, and reductions in total VLDL and medium VLDL particles for those consuming EGG compared to SUB (P<0.05). Plasma insulin and insulin resistance (HOMA-IR) were reduced, while LCAT activity, and both HDL and LDL diameters increased over time in the EGG group only (P<0.05). ConclusionsIncorporating daily whole egg intake into a moderately carbohydrate-restricted diet provides further improvements in the atherogenic lipoprotein profile and in insulin resistance in individuals with MetS.

Effect of ProAlgaZyme on plasma lipid profile in diet induced hypercholesterolemic hamsters

Increased plasma LDLc and low HDLc are associated with risk of cardiovascular disease (CVD), the leading cause of death worldwide. This study investigated the effect of an algae infusion, ProAlgaZyme(P) and its sub‐fractions on plasma lipids in hamster model. Sixty (n=10/group) male Golden Syrian hamsters (8 w old) fed a high fat diet (30% calories from fat) were randomized into 6 groups: control, P and its subfractions P1, P2, P3, and P4. The infusion (20% v/v) was added to the drinking water of all experimental groups, while the control animals received water. Total cholesterol (TC), HDLc, phospholipids, and cholesterol ester levels were assayed enzymatically after 4 weeks. LDLc was significantly reduced in P (p&lt;0.05), P3 and P4 (p&lt;0.001) as compared to the control, while HDL was considerably increased in P, P3 and P4 groups (p&lt;0.001). Moreover, the TC/HDLc ratio was significantly lower in all experimental animals (P, P1, P2 p&lt;0.05; P3, P4 p&lt;0.001). The shift in plasma cholesterol towards the higher density fractions was validated by density gradient ultracentifugation. Also, the HDL diameter was significantly increased in P3 and P4, as compared with control (p&lt;0.05). This has been associated with protection against CVD. Thus, intake of ProAlgaZyme and its sub‐fractions significantly improved plasma lipid profile by lowering LDLc and increasing HDLc. This may potentially provide benefits in cardiovascular health.Grant Funding Source : Health Enhancement Products Inc.

Consumption of High-Oleic Acid Ground Beef Increases HDL-Cholesterol Concentration but Both High- and Low-Oleic Acid Ground Beef Decrease HDL Particle Diameter in Normocholesterolemic Men

On the basis of previous results from this laboratory, this study tested the hypothesis that ground beef high in MUFA and low in SFA would increase the HDL-cholesterol (HDL-C) concentration and LDL particle diameter. In a crossover dietary intervention, 27 free-living normocholesterolemic men completed treatments in which five 114-g ground beef patties/wk were consumed for 5 wk with an intervening 4-wk washout period. Patties contained 24% total fat with a MUFA:SFA ratio of either 0.71 (low MUFA, from pasture-fed cattle) or 1.10 (high MUFA, from grain-fed cattle). High-MUFA ground beef provided 3.21 g more 18:1(n-9), 1.26 g less 18:0, 0.89 g less 16:0, and 0.36 g less 18:1(trans) fatty acids per patty than did the low-MUFA ground beef. Both ground beef interventions decreased plasma insulin and HDL2and HDL3particle diameters and increased plasma 18:0 and 20:4(n-6) (allP≤ 0.05) relative to baseline values. Only the high-MUFA ground beef intervention increased the HDL-C concentration from baseline (P= 0.02). The plasma TG concentration was positively correlated with the plasma insulin concentration (r= 0.40;P< 0.001) and negatively correlated with HDL-C (r= -0.47;P< 0.001) and plasma 18:0 (r= -0.24;P< 0.01). Plasma insulin and HDL diameters were not correlated (r= 0.01;P> 0.50), indicating that reductions in these measures were not coordinately regulated. The data indicate that dietary beef interventions have effects on risk factors for cardiovascular disease that are independent (insulin, HDL diameters) and dependent (HDL-C) on beef fatty acid composition.

A clustering analysis of lipoprotein diameters in the metabolic syndrome

BackgroundThe presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle diameters with components of the metabolic syndrome (MetS), although this has been the focus of less research. We aimed to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by clustering individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three fractions of lipoprotein into a unified phenotype.MethodsWe used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a general population sample of 1,036 adults (mean ± SD, 48.8 ± 16.2 y of age). Using latent class analysis, the sample was grouped by the diameter of their fasting lipoproteins, and mixed effects models tested whether the distribution of MetS components varied across the groups.ResultsEight discrete groups were identified. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One of those two groups, one was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides, and waist circumference (WC; P < .001). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. These associations held after additionally controlling for VLDL, LDL and HDL particle concentrations.ConclusionsWhile small LDL diameters remain associated with IR and the MetS, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. If replicated, the association of this phenotype with more severe IR-features indicated that it may contribute to identifying of those most at risk for incident type II diabetes and cardiometabolic disease.

Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

BackgroundPrevious analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), ~75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all P < .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177) and S447X (rs328).FindingsMixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (P = .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; P = .04).ConclusionsThis was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.

Response of Lipoprotein Particle Diameters and Distributions Following Aerobic Exercise and Omega-3 Fatty Acid Supplementation

Small, dense LDL particles have been associated with an increased cardiovascular disease risk. Both aerobic exercise and omega-3 fatty acid (ω-3fa) supplementation have been shown to favorably alter lipid and lipoprotein concentrations. Little data exist documenting the combined effects of aerobic exercise and ω-3fa supplementation on lipoprotein particle diameters and relative cholesterol distributions. The poly acrylamide gel electrophoresis (PAGE) technique has been shown to quantify both the peak particle diameters and the percent or relative distribution of LDL and HDL cholesterol among LDL and HDL subfractions, respectively. PURPOSE: To determine the independent and combined effect of aerobic exercise and ω-3fa supplementation on LDL and HDL particle diameters and relative cholesterol distributions. METHODS: Moderately active, non-smoking men (n=11; mean±SD, agey 30.5±10.0 yrs, Ht=179.3±10.9 cm, Wt=85.4±11.2 kg, BMI=26.7±3.8 kgm−2, VO2peak=40.8±6.5 mL-kg-min1) were recruited. Each participant performed four randomized trials: rest-no-supplement, exercise-no-supplement, rest±supplement, and exercise±supplement. Exercise consisted of three consecutive days of treadmill exercise at ∼70%VO peak for 60 minutes, and rest consisted of three consecutive days of no exercise. Supplementation consisted of 42 d of 4.55 g-d1 of ω-3fa. Fasting (10h) blood samples were collected 14–16 h following the third exercise and rest sessions in both of the supplement and no supplement trials. Using a 2–31% non-denaturing PAGE, LDL, HDL, HDL, HDL, and HDL peak diameters were quantified. The > relative distribution of cholesterol was quantified by measuring the area under the lipoprotein peaks. A 2 × 2 (exercise × supplement) ANO VA with repeated measures with a Bonferroni post hoc test were employed. The criterion reference for statistical significance was set at a p<0.05. RESULTS: Exercise promoted a significant increase in LDL diameter (26.1 nm to 26.4 nm), but not in HDL diameter. The relative distribution of cholesterol in LDL subfractions was not altered. Supplementation of the ω-3fa resulted in a significant shift in the distribution of cholesterol carried by HDL2 (12.3%) and HDL3 (−22.8%). The majority of this shift was noted inHDL2b (17.4%) and HDL3a (−30.8%). There were no combined effects of exercise and ω-3fa supplementation on lipoprotein particles. CONCLUSION: These data suggest that three consecutive days of aerobic exercise will promote a favorable change in LDL particle diameter. In addition, ω-3fa supplementation may promote a change in the distribution of cholesterol between HDL3 and HDL2 particles.

Evidence that endothelial lipase remodels high density lipoproteins without mediating the dissociation of apolipoprotein A-I

Endothelial lipase (EL) is a triglyceride lipase gene family member that has high phospholipase and low triglyceride lipase activity. The aim of this study was to determine whether the phospholipase activity of EL is sufficient to remodel HDLs into small particles and mediate the dissociation of apolipoprotein A-I (apoA-I). Spherical, reconstituted HDLs (rHDLs) containing apoA-I only [(A-I)rHDLs], apoA-II only [(A-II)rHDLs], or both apoA-I and apoA-II [(A-I/A-II) rHDLs] were prepared. The rHDLs, which contained only cholesteryl esters in their core and POPC on the surface, were incubated with EL. As the rHDLs did not contain triacylglycerol, only the POPC was hydrolyzed. Hydrolysis was greater in the (A-I/A-II)rHDLs than in the (A-I)rHDLs. The (A-II)rHDL phospholipids were not hydrolyzed by EL. EL remodeled the (A-I)rHDLs and (A-I/A-II)rHDLs, but not the (A-II)rHDLs, into smaller particles. The reduction in particle size was related to the amount of phospholipid hydrolysis, with the diameter of the (A-I/A-II)rHDLs decreasing more than that of the (A-I)rHDLs. These changes did not affect the conformation of apoA-I, and neither apoA-I nor apoA-II dissociated from the rHDLs. Comparable results were obtained when human plasma HDLs were incubated with EL. These results establish that the phospholipase activity of EL remodels plasma HDLs and rHDLs into smaller particles without mediating the dissociation of apolipoproteins.

Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort: associations with gender and glycemia.

To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes. In the 1997-1999 Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort, serum from 428 women and 540 men were characterized by conventional lipids, NMR, apolipoprotein levels, and LDL susceptibility to in vitro oxidation. Simple and partial correlation coefficients were calculated for each lipoprotein-related parameter versus gender, with and without covariates (age, diabetes duration, concurrent HbA(1c), DCCT randomization, hypertension, BMI, waist-to-hip ratio, and albuminuria). For concurrent HbA(1c), data were analyzed as above, exchanging gender for HbA(1c). Associations were significant if P < 0.05. Although men and women had similar total and LDL cholesterol and triglycerides, men exhibited the following significant percent differences in NMR profiles versus women: small VLDL 41; IDL -30; medium LDL 39; small LDL 21; large HDL -32; small HDL 35; LDL particle concentration 4; VLDL and HDL diameters -8 and -4, respectively. Small VLDL, small HDL, medium LDL (women only), small LDL (men only), and LDL particle concentration were positively correlated, and HDL size was inversely correlated, with concurrent HbA(1c). NMR profile was unrelated to prior DCCT randomization. Susceptibility of LDL to oxidation was unrelated to gender and glycemia. Male gender and poor glycemia are associated with a potentially more atherogenic NMR lipoprotein profile. Neither gender nor glycemia influence LDL oxidation in vitro.