Determination of sex differences requires formal test for differences: Comment on "lipoprotein-subclass particle numbers in children with abdominal obesity".
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ABSTRACT:
SUBMITTER: Vorland CJ
PROVIDER: S-EPMC10033381 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Determination of sex differences requires formal test for differences: Comment on "lipoprotein-subclass particle numbers in children with abdominal obesity".
Vorland Colby J CJ Golzarri-Arroyo Lilian L Maney Donna L DL Brown Andrew W AW
Pediatrics international : official journal of the Japan Pediatric Society 20230101 1
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Project description:BackgroundRaising the cholesterol of high-density lipoprotein (HDL) particles is targeted as a cardiovascular disease prevention strategy. However, HDL particles are heterogeneous in composition and structure, which may relate to differences in antiatherogenic potential. We prospectively evaluated the association of HDL subclasses, defined by a recently proposed nomenclature, with incident coronary heart disease (CHD).Methods and resultsBaseline HDL particle concentrations were measured by nuclear magnetic resonance spectroscopy and categorized into 5 subclasses (very large, large, medium, small, and very small) among 26 332 initially healthy women. During a median follow-up of 17 years, 969 cases of incident CHD (myocardial infarction, revascularization, and CHD death) were ascertained. In Cox models that adjusted for age, race/ethnicity, blood pressure, smoking, postmenopausal status, and hormone therapy, associations with incident CHD were inverse (P trend<0.0001) for concentrations of very large (hazard ratio for top versus bottom quartile, 0.49; 95% confidence interval, 0.41-0.60), large (0.54; 0.45-0.64), and medium (0.69; 0.58-0.83) HDL subclasses. Conversely, hazard ratios (95% confidence intervals) for small and very small HDL were 1.22 (1.01-1.46; P trend=0.08) and 1.67 (1.39-2.02; P trend<0.0001), respectively. However, after additionally adjusting for metabolic and lipoprotein variables, associations for the spectrum of large, medium, and small HDL subclasses were inverse (P trend<0.05 for large and small and 0.07 for medium), whereas subclasses at either end of the spectrum were not associated with CHD (P trend=0.97 for very large and 0.21 for very small HDL).ConclusionsIn this prospective study, associations with incident CHD differed by HDL particle subclass, which may be relevant for developing HDL-modulating therapies.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
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Project description:Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH.
| S-EPMC4242459 | biostudies-literature
Project description:We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.
| S-EPMC3800263 | biostudies-literature
Project description:BackgroundIt is unclear how high-protein (HP) and high-monounsaturated fat (HMF) meals affect postprandial blood lipids and lipoprotein particle numbers (LPN).PurposeTo compare a HP versus a HMF meal on postprandial lipid and LPN responses.MethodsTwenty-four participants (age: 36.3±15.0 years; body mass index: 23.6±2.0 kg/m2; 45.8% female) were fed a HP (31.9% energy from protein) and a HMF (35.2% fat and 20.7% monounsaturated fat) meal in a randomized cross-over trial design. Energy and carbohydrate content were the same across meals. Blood samples were drawn in the fasting state and 3 hour postprandial state, and assessed for lipids and LPN.ResultsRepeated measures analysis showed a significant (p<0.05) treatment by time interaction effect for triglycerides (TG), the primary variable, total high-density lipoprotein particles (T-HDLP) and T-HDLP minus large-buoyant high-density lipoprotein 2b (T-HDLP-LB-HDL2b). HP versus HMF condition led to significantly lower TG at 120 (geometric mean: 90.1 (95% confidence interval (CI): 76.4-106.3) vs. 146.5 (124.2-172.9) mg/dL) and 180 (101.4 (83.1-123.8) vs. 148.7 (121.9-181.4) mg/dL) min and higher T-HDLP at 120 (mean difference: 297.3 (95% CI: 48.6-545.9) nmol/L) and 180 (291.6 (15.8-567.5) nmol/L) min. The difference in T-HDLP by condition was due to the significantly higher small-dense HDLP (T-HDLP-LB-HDL2b) during HP versus HMF condition at 120 (mean difference: 452.6 (95% CI: 177.4-727.9) nmol/L) and 180 (496.8 (263.1-730.6) nmol/L) min. Area under the curve analysis showed that HP versus HMF condition led to significantly lower TG, non-HDLP, and very-low-density lipoprotein particles (VLDLP) responses but significantly less favorable responses in LB-HDL2b particles, T-HDLP-LB-HDL2b, and LB-HDL2b/T-HDLP ratio.ConclusionThe HP meal led to lower TG, non-HDLP, and VLDLP but less favorable LB-HDL2b, small-dense HDLP, and LB-HDL2b/T-HDLP ratio responses versus a HMF meal. Further studies are needed to confirm these findings over multiple meals.
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Project description:BackgroundEvidence suggests that lipoprotein subclass particles are critical markers of cardiovascular disease (CVD) risk. Older women have increased CVD risk related to age. The purpose of this study was to determine whether low and moderate doses of exercise influence lipoprotein subclasses.MethodsWomen (60-75 years) were randomized into groups for 16 weeks of moderate-intensity exercise training at a low or moderate dose (33.6 and 58.8 kJ/kg body weight weekly, respectively). Lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy before and after the training.ResultsThe average weekly exercise duration was 109 and 164 min, for low- and moderate-dose groups, respectively. In the low-dose group, high-density lipoprotein particle (HDL-P) concentration decreased (Δ = -1.9 ± 3.1 µmol/L, mean ± SD, p = 0.002) and mean HDL-P size increased (Δ = 0.1 ± 0.3 nm, p = 0.028). In the moderate-dose group, mean HDL-P size (Δ = 0.1 ± 0.2 nm; p = 0.024) and low-density lipoprotein particle size increased (Δ = 0.4 ± 3.9 nm; p = 0.007). Baseline body mass index, peak oxygen consumption and age were associated with changes in a few lipoprotein subclasses.ConclusionsIn this sample of inactive older women, moderate-intensity exercise training at a dose equivalent to or even lower than the minimally recommended level by public health agencies induced changes in lipoprotein subclasses in line with reduced CVD risk. However, higher doses are encouraged for greater health benefits.
| S-EPMC10742846 | biostudies-literature
Project description:An integrative analysis of human biofluid data in the exRNA Atlas revealed the existence of distinct extracellular RNA cargo types. To gain further insight on the biological nature of these cargo types, we correlated exRNA Atlas cargo profiles with a variety of other RNA-seq profiles. This study focuses on lipoprotein particle (LPP) exRNA profiles obtained via sequential density ultracentrifugation (SD-UC) and fast protein liquid chromatography (FPLC).
2018-12-20 | GSE124131 | GEO
Project description:Early diagnosis is essential for improving the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aims to explore the clinical value of lipoprotein subfractions in the diagnosis of hepatitis B virus (HBV)-related HCC. Lipoprotein subfractions were detected by 1H-NMR spectroscopy, and the pattern-recognition method and binary logistic regression were performed to classify distinct serum profiles and construct prediction models for HCC diagnosis. Differentially expressed proteins associated with lipid metabolism were detected by LC-MS/MS, and the potential prognostic significance of the mRNA expression was evaluated by Kaplan-Meier survival analysis. The diagnostic panel constructed from the serum particle number of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL-1~LDL-6) achieved higher accuracy for the diagnosis of HBV-related HCC and HBV-related benign liver disease (LD) than that constructed from serum alpha-fetoprotein (AFP) alone in the training set (AUC: 0.850 vs. AUC: 0.831) and validation set (AUC: 0.926 vs. AUC: 0.833). Furthermore, the panel achieved good diagnostic performance in distinguishing AFP-negative HCC from AFP-negative LD (AUC: 0.773). We also found that lipoprotein lipase (LPL) transcript levels showed a significant increase in cancerous tissue and that high expression was significantly positively correlated with the poor prognosis of patients. Our research provides new insight for the development of diagnostic biomarkers for HCC, and abnormal lipid metabolism and LPL-mediated abnormal serum lipoprotein metabolism may be important factors in promoting HCC development.
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Project description:BackgroundAbnormalities in traditional lipids, particularly decreased HDL cholesterol and increased triglycerides, can precede the onset of hypertension. Whether lipoprotein particle size or subclass concentrations play a role in the development of hypertension is unknown.MethodsWe followed 17 527 initially healthy women without baseline hypertension prospectively for 8 years. At baseline, information regarding traditional lipids and hypertension risk factors was obtained, and lipoprotein size and subclass concentrations were measured by nuclear magnetic resonance spectroscopy.ResultsBaseline lipoprotein size and subclass concentrations were significantly associated with incident hypertension. Although LDL cholesterol was not associated with hypertension [odds ratio (OR) for quintile 5 vs 1: 1.08 (95% CI 0.96-1.20)], increased concentrations of LDL particles were associated with greater risk [OR 1.73 (1.54-1.95)], especially small LDL particles [OR 1.62 (1.45-1.83)]. Increased HDL cholesterol was associated with lower risk of hypertension [OR for quintile 5 vs 1: 0.79 (0.70-0.89)]. By contrast, increased concentrations of HDL particles had greater risk [OR 1.48 (1.32-1.67)], especially small HDL particles [OR 1.36 (1.22-1.53)], whereas large HDL particles had lower risk [OR 0.80 (0.71-0.90)]. Triglycerides and triglyceride-rich VLDL particles were positively associated with hypertension, with large VLDL particles associated with greater risk [OR 1.68 (1.50-1.89)]. Adding particle subclasses improved discrimination over a model with traditional lipids and risk factors (c-statistic 0.671 compared to 0.676; P < 0.001).ConclusionsIn this study of initially healthy women, lipoprotein particle size and subclass concentrations were associated with incident hypertension and provided additive information to traditional lipids and risk factors.
| S-EPMC3153909 | biostudies-literature
Project description:BackgroundSome patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.ResultsBoth treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.ConclusionsWhen assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.Trial registration(Registered at clinicaltrials.gov: Clinical trial # NCT00276484).
| S-EPMC3012666 | biostudies-literature
Project description:The interactions of Bcl-2 family proteins with intracellular lipids are essential for the regulation of apoptosis, a mechanism of programmed cell death that is central to the health and development of multicellular organisms. Bid and its caspase-8 cleavage product, tBid, promote the permeabilization of the mitochondrial outer membrane and sequester antiapoptotic Bcl-2 proteins to counter their cytoprotective activity. Bid and tBid also promote lipid exchange, a characteristic trait of apoptosis. Here, we show that tBid is capable of associating with phospholipids to form soluble, nanometer-sized lipoprotein particles that retain binding affinity for the antiapoptotic protein Bcl-xL. The tBid lipoprotein particles form with a lipid/protein stoichiometry in the range of 20/1 and have a diameter of ∼11.5 nm. Lipoparticle-bound tBid retains an α-helical structure and binds Bcl-xL through its third Bcl-2 homology motif, forming a soluble, lipid-associated heteroprotein complex. The results shed light on the role of lipids in mediating Bcl-2 protein mobility and interactions.
| S-EPMC6084415 | biostudies-literature