Low Density Lipoprotein Fraction Research Articles

Improving nutrient digestibility and health in rabbits: effect of fermented rapeseed meal supplementation on haematological and lipid parameters of blood

BackgroundMany studies conducted on livestock point to fermented rapeseed meal (FRSM) as a component that provides adequate quality and quantity of protein. Additionally, it is a very good source of probiotics, prebiotics, enzymes, and antioxidants. A study was undertaken to assess the impact of a feed supplemented with FRSM fermented with Bacillus subtilis strain 87Y on production parameters, nutrient digestibility, and haematological and lipid indicators of the blood in growing rabbits. Forty New Zealand White rabbits (body weight 816,25 ± 24,98 g) aged 35 days were used in this study. The animals were divided into four groups, a control group (C) was fed a standard diet, while in the diet of three experimental groups, soybean meal (SBM) was replaced with FRSM at 4% (FR4 group), 8% (FR8 group), or 12% (FR12 group).ResultsDetailed analysis revealed that the contribution of FRSM in the rabbit feed, regardless of the amount, had a significant effect on body weight gain (BWG), as well as average daily gain (ADG), compared to the control group (C), (P = 0.017). All groups receiving FRSM had a significantly lower (P = 0.05) feed conversion ratio (FCR) compared to the control group. In rabbits fed a diet containing 8% FRSM, the blood haematological parameters, such as red blood cells (RBC), haematocrit (HCT), haemoglobin (HGB), and mean corpuscular volume (MCV), were significantly higher compared to the control group (P = 0.037). In addition, a significant reduction in the plasma levels of the low-density lipoprotein fraction (LDL-chol), the ratio of total cholesterol to high-density lipoprotein (CHOL/HDL), (P = 0.001), and triacylglycerols (TG), (P = 0.004) were observed in the experimental groups compared to the control group.ConclusionsBased on the encouraging outcomes, it is possible to recommend domestically produced FRSM as a viable substitute for genetically-modified (GM) SBM in rabbit feed.

The Effect of Lower Limb Pressotherapy Treatment on Selected Rheological and Biochemical Indices of Blood in Young, Healthy Women.

Background: Intermittent pneumatic compression is a non-invasive therapeutic technique that has been gaining popularity in recent years due to its potential use in many areas of medicine. It can be successfully used alone or in combination with other therapeutic methods. The aim of this study was to investigate whether and how a series of pressotherapy treatments on the lower limbs affects the rheological properties of blood (blood count, red blood cell deformability and aggregation, and blood viscosity), lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), and renal profile (urea, creatinine, and estimated glomerular filtration rate) in young, healthy women. Methods: The study group consisted of 15 healthy women aged 20-26 (22.5 ± 1.5), without chronic diseases and not practicing competitive sports. The participants underwent a series of 10 lower limb pressotherapy treatments. A single treatment lasted 30 min and each time the pressure used during the treatment was individually selected according to the participants' preference. The first blood test was performed a week before the treatments; the second on the day of the start of treatment, but before the pneumatic massage; the third after the completed series of pressotherapy treatments; and the fourth a week after the completed series of treatments. Results: In the conducted study, the analysis of the values of the complete blood count showed the following: a significant decrease in red blood cell count, hemoglobin, average hemoglobin concentration in erythrocytes, average red blood cell volume, average hemoglobin mass in red blood cells; a significant increase in average red blood cell volume; and an average hemoglobin mass in red blood cells. The analysis of the values of rheological parameters showed the following: a significant decrease in elongation indices 0.58, 1.13, 4.24, 15.95, 30.94, and 60.00; blood viscosity; the aggregation index; the degree of complete aggregation; and a significant increase in elongation indices 0.30, 1.13, 8.23, 30.94, 60.00; blood viscosity; the degree of complete aggregation; and the half-time of complete aggregation. A decrease in the concentration of low-density lipoprotein and high-density lipoprotein fractions was also noted. No significant changes were found in the values of total cholesterol and triglycerides, as well as in renal profile elements. Conclusions: The application of a series of 10 lower limb pressotherapy treatments has a beneficial effect, with a decrease in blood viscosity and the aggregation index, and an increase in the elongation index at shear stress from 0.30 [Pa] to 8.23 [Pa] in young, healthy women. A series of 10 lower limb pressotherapy treatments may affect the decrease in the values at high shear stress forces of 30.95 [Pa] and from 60.00 [Pa] in young, healthy women. The use of a series of 10 lower limb pressotherapy treatments increases the values of hemoglobin, the average red blood cell volume, and the average hemoglobin concentration in erythrocytes, and also reduces the values of red blood cell count, average hemoglobin mass in red blood cells and low-density lipoproteins and high-density lipoproteins in young, healthy women (it also does not cause any adverse changes). The use of pressotherapy on the lower limbs seems to be an effective element of the multi-component prevention of circulatory system diseases.

Short-term impact of vitamin K2 supplementation on biochemical parameters and lipoprotein fractions.

This study explored the short-term effects of vitamin K2 (VK2) supplementation on biochemical parameters (vitamin D, vitamin E, vitamin A, alkaline phosphatase, calcium, phosphorus (P), magnesium, metallothionein, triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lipoprotein fractions (albumin, HDL, very low-density lipoprotein (VLDL), LDL, and chylomicrons). A short-term experiment (24h, six probands) was performed to track changes in VK2 levels after a single-dose intake (360µg/day). Liquid chromatography-tandem mass spectrometry was used to monitor vitamin K levels (menaquinone-4 (MK-4), menaquinone-7 (MK-7), and vitamin K1 [VK1]) with a limit of detection of 1.9pg/mL for VK1 and 3.8pg/mL for the two forms of VK2. Results showed that MK-7 levels significantly increased within 2-6h post-administration and then gradually declined. MK-4 levels were initially low, showing a slight increase, whereas VK1 levels rose initially and then decreased. Biochemical analyses indicated no significant changes in sodium, chloride, potassium, calcium, magnesium, albumin, or total protein levels. A transient increase in P was observed, peaking at 12h before returning to baseline. Agarose gel electrophoresis of lipoprotein fractions revealed distinct chylomicron bands and variations in VLDL and HDL mobility, influenced by dietary lipids and VK2 supplementation. These findings suggest effective absorption and metabolism of MK-7 with potential implications for bone metabolism and cardiovascular health.

Cholesterol-Lowering and Antioxidant Effects of Pork-Liver Protein Hydrolysate in Otsuka Long-Evans Tokushima Fatty Rats.

In this study, we investigated the effects of a porcine liver protein hydrolysate (PLH) diet on lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type II diabetes. OLETF rats (20-wk-old males) were pair-fed with either a PLH diet containing 20% PLH or a casein diet for 14 wk. Dietary PLH significantly lowered serum cholesterol and phospholipid concentrations, mainly by decreasing low-density lipoprotein and high-density lipoprotein fractions. Fecal cholesterol was significantly increased in the PLH diet group; however, the total bile acid concentration in the feces was not significantly different between the groups. In addition, the PLH diet significantly decreased serum thiobarbituric acid reactive substance concentrations. These results suggest that dietary PLH exerts hyperlipidemic and antioxidant effects, indicating that it is a novel functional food ingredient.

NMR-Based Analysis of Plasma Lipoprotein Subclass and Lipid Composition Demonstrate the Different Dietary Effects in ApoE-Deficient Mice.

Plasma lipid levels are commonly measured using traditional methods such as triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CH). However, the use of newer technologies, such as nuclear magnetic resonance (NMR) with post-analysis platforms, has made it easier to assess lipoprotein profiles in research. In this study involving ApoE-deficient mice that were fed high-fat diets, significant changes were observed in TG, CH, free cholesterol (FC), and phospholipid (PL) levels within the LDL fraction. The varied proportions of TG in wild-type mice and CH, FC, and PL in ApoE-/- mice were strikingly different in very low-density lipoproteins (VLDL), LDL, intermediate-density lipoprotein (IDL), and HDL. This comprehensive analysis expands our understanding of lipoprotein subfractions and the impacts of the APOE protein and high-fat diet in mouse models. The new testing method allows for a complete assessment of plasma lipids and their correlation with genetic background and diet in mice.

Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers.

Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life-threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. Cross-sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride-rich lipoprotein (TRL) and low-density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low-to-intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low-to-intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.

Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat

BackgroundThe apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging.ResultsApoE−/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats.ConclusionThese data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.

Self-Association of Von Willebrand Factor (VWF) into Prothrombotic Fibers Is Most Potently Enhanced By the Highly Atherogenic Small, Dense Fraction of Low-Density Lipoprotein (sd-LDL)

We recently demonstrated that plasma lipoproteins play a major role in regulating the function of the hemostatic system by either inhibiting or promoting the self-association of von Willebrand factor (VWF) into large fibers and bundles that are hyperadhesive for platelets. Such fibers can form on the surface of activated endothelium such as during thrombotic microangiopathies. We showed that high-density lipoprotein (HDL) attenuates VWF self-association and reduces the formation of VWF-platelet thrombi, both in vitro and in mice (PMID:26552698). By contrast, low-density lipoprotein (LDL) enhances VWF self-association and promotes the formation of VWF-platelet thrombi ( Blood, in press). Consequently, wild-type mice with elevated plasma LDL display intense and prolonged VWF-platelet thrombosis in stimulated mesenteric microvessels, exceeding even the thrombosis observed in ADAMTS13-deficient mice with normal LDL levels. All the lipoproteins of low density carry apolipoprotein (apo) B100 and comprise fractions of very low density (VLDL), intermediate density (IDL), and low density (LDL). The LDL fraction comprises two subfractions: small-dense (sd) LDL and large-buoyant (lb) LDL. Epidemiologic studies suggest that sd-LDL is the most atherogenic subfraction (PMID:33586462). Another atherogenic lipoprotein also carries apoB-100, Lp(a), in which the apoB-100 is complexed with apo(a). Here, we sought to determine the effect of LDL subfraction(s) on VWF self-association. We isolated LDL, sd-LDL and lb-LDL from healthy donor plasma by sequential KBr density centrifugation. Lp(a) was purified from patients with high circulating Lp(a) (&amp;gt;50 mg/dL) as described by Mueller et al. (PMID:35650291). We first tested these lipoproteins in microfluidic devices adapted from the design of Herbig and Diamond (PMID:26178390). In these devices, high shear stress and flow acceleration are generated around a 30-um-wide pillar within a 60-um-wide flow channel and induce the attachment and self-association of VWF into fibers on and around the pillar. We quantified VWF fiber accumulation from differential interference contrast (DIC) images. Of all the lipoprotein fractions, sd-LDL was the most potent in accelerating VWF strand accumulation (see figure). The effect of lipoproteins in this device correlated with their impact on microvascular thrombosis in vivo. We infused apoB100-containing lipoproteins into wild-type mice (3-4 weeks old) before inducing VWF-platelet thrombi deposition in the mesenteric microvasculature with ionophore. All the apoB100 lipoproteins enhanced microvascular thrombosis [we did not test Lp(a), which had no effect in the microfluidic channel], but sd-LDL was by far the most potent; the treated mice had twice the number of large thrombi (&amp;gt;30-um diameter) as the mice treated with an equivalent quantity of lb-LDL. The effect also persisted for much longer before returning to baseline with the sd-LDL. We have explored possible reasons why sd-LDL is so much more potent. Compared to the other apoB-containing lipoproteins, sd-LDL is smaller and denser, with a greater surface curvature. Whether this fact changes accessibility to sites on apoB100 is not known. We also compared the lipidomes and proteomes of sd-LDL and lb-LDL for clues to the difference. Compared to lb-LDL, sd-LDL contained a much higher content of cholesterol and cholesterol esters per particle. The proteomes of the two particles were also different, with several proteins being more abundant in lb-LDL, in particular apoC-III, apoE, apoA-IV, and apoC-II. Only apoF was significantly more abundant in sd-LDL. We are currently testing to determine if any of these difference accounts for the differences between the two LDL subfractions in promoting VWF self-association. In summary, we show that the lipoprotein associated with the greatest atherosclerotic burden and most cardiovascular disease is also the one with the most potent effect in promoting a prothrombotic state by enhancing VWF self-association. These findings have important implications for the development of the atherosclerotic lesion, the formation of the thrombus after the lesion ruptures, and for the microvascular dysfunction often observed after revascularization.

Depleting LCAT Aggravates Atherosclerosis in LDLR-deficient Hamster with Reduced LDL-Cholesterol Level

IntroductionLecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. ObjectivesTo better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. MethodsPlasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. ResultsOn HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. ConclusionsOur study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

ANGPTL3 (Angiopoietin-Like 3) Preferentially Resides on High-Density Lipoprotein in the Human Circulation, Affecting Its Activity.

Background ANGPTL3 (angiopoietin-like protein 3) is an acknowledged crucial regulator of lipid metabolism by virtue of its inhibitory effect on lipoprotein lipase and endothelial lipase. It is currently unknown whether and to which lipoproteins ANGPTL3 is bound and whether the ability of ANGPTL3 to inhibit lipase activity is affected by binding to lipoproteins. Methods and Results Incubation of ultracentrifugation-isolated low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions from healthy volunteers with recombinant ANGPTL3 revealed that ANGPTL3 associates with both HDL and LDL particles ex vivo. Plasma from healthy volunteers and a patient deficient in HDL was fractionated by fast protein liquid chromatography, and ANGPTL3 distribution among lipoprotein fractions was measured. In healthy volunteers, ≈75% of lipoprotein-associated ANGPTL3 resides in HDL fractions, whereas ANGPTL3 was largely bound to LDL in the patient deficient in HDL. ANGPTL3 activity was studied by measuring lipolysis and uptake of 3H-trioleate by brown adipocyte T37i cells. Unbound ANGPTL3 did not suppress lipase activity, but when given with HDL or LDL, ANGPTL3 suppressed lipase activity by 21.4±16.4% (P=0.03) and 25.4±8.2% (P=0.006), respectively. Finally, in a subset of the EPIC (European Prospective Investigation into Cancer) Norfolk study, plasma HDL cholesterol and amount of large HDL particles were both positively associated with plasma ANGPTL3 concentrations. Moreover, plasma ANGPTL3 concentrations showed a positive association with incident coronary artery disease (odds ratio, 1.25 [95% CI, 1.01-1.55], P=0.04). Conclusions Although ANGPTL3 preferentially resides on HDL, its activity was highest once bound to LDL particles.

PB0807 The Small, Dense Fraction of Low-Density Lipoprotein (LDL) is the Only Plasma Lipoprotein Capable of Enhancing von Willebrand Factor (VWF) Self-Association

PB0807 The Small, Dense Fraction of Low-Density Lipoprotein (LDL) is the Only Plasma Lipoprotein Capable of Enhancing von Willebrand Factor (VWF) Self-Association

Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans

The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. We recently identified SPRING as a post-transcriptional regulator of SREBP activation. Constitutive or inducible global ablation of Spring in mice is not tolerated, and we therefore develop liver-specific Spring knockout mice (LKO). Transcriptomics and proteomics analysis reveal attenuated SREBP signaling in livers and hepatocytes of LKO mice. Total plasma cholesterol is reduced in male and female LKO mice in both the low-density lipoprotein and high-density lipoprotein fractions, while triglycerides are unaffected. Loss of Spring decreases hepatic cholesterol and triglyceride content due to diminished biosynthesis, which coincides with reduced very-low-density lipoprotein secretion. Accordingly, LKO mice are protected from fructose diet-induced hepatosteatosis. In humans, we find common genetic SPRING variants that associate with circulating high-density lipoprotein cholesterol and ApoA1 levels. This study positions SPRING as a core component of hepatic SREBP signaling and systemic lipid metabolism in mice and humans.

Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D

BackgroundEffective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis.MethodsWe performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated.ResultsProfilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study.ConclusionPFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

Observation of severe pediatric inflammatory multisystem syndrome associated with COVID-19

One of the rare manifestations of COVID-19 is pediatric inflammatory multisystem syndrome, most often in publications it is found out how pediatric inflammatory multisystem syndrome in children (РIMS). The progression of the inflammatory response in РIMS may be a consequence of the development of secondary hemophagocytic syndrome, a significant part of which is refractory fever, an increase in ferritin, AST and ALT, cytopenia, an increase in interleukin 6, severe hepatic and neurological dysfunction. The case with this group of representatives of other multiple organ failure manifestations in the detection of acute distress syndrome and acute heart failure, in the detection of the development of myocarditis.&#x0D; A feature of the described clinical detection is the dynamic observation of a severe pediatric multisystem inflammatory syndrome associated with COVID-19, complicated by myocarditis with acute heart failure, left ventricular dysfunction and secondary hemophagocytic syndrome, in an 11-year-old girl with underlying obesity. The child is taking triple therapy with glucocorticosteroids in combination with intravenous immunoglobulin and cyclosporine A, with an expected effect on the ongoing treatment. Possible features of observation are noted: 1) a very early start of РIMS during the acute phase of СOVID-19; 2) transient dyslipidemia at the onset of РIMS with an increase in cholesterol, mainly due to the low-density lipoprotein fraction, and spontaneous regression without lipid-lowering drugs; 3) MRI signs of myocarditis in a month after the onset of the disease, despite the normalization of echocardiography and pro-BNP.

Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes

BackgroundHigher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins.MethodsNuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR).ResultsThe majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer’s disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C).ConclusionsThe cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.

Effects of Dietary Halloysite Supplementation on Broiler Chicken’s Blood Parameters, Carcass and Meat Quality, and Bone Characteristics: A Preliminary Study

Abstract The aim of this study was to determine the effect of halloysite supplementation to the complete diets for broiler chickens on selected blood parameters, carcass and organ characteristics, as well as bone and meat traits. The trial was conducted under experimental conditions in a large-scale poultry farm on 18,000 broiler chickens. The one-day broiler Ross 308 chicks were randomly divided into two groups: control (C) and experimental (E) in an amount of 9,000 birds per group. In each group, chicks were separated into five pens (100 m2) with 1800 chicks per pen. The birds were fed granulated complete mixtures without (C group) or with halloysite (E group) distributed in an amount of 1% (based on fresh matter) from the 11 d of life. Analysis revealed that halloysite supplementation to the broiler diet at the level of 1% showed a trend (P = 0.056) towards higher final body weight, significantly improved carcass yield (P = 0.048), and reduced the relative weights of the liver and gizzard (P&lt;0.05). No differences (P&gt;0.05) were observed either in terms of the physicochemical parameters of the broiler chickens’ breast muscles, except a significantly lower b* value of the colour parameter (P = 0.048). In turn, in the blood serum, the addition of 1% halloysite significantly decreased (P&lt;0.05) the content of triglycerides and the total cholesterol and low-density lipoprotein fraction, but did not affect (P&gt;0.05) the high-density lipoprotein fraction, calcium, phosphorus or alkaline phosphate content. Tibia and femur characteristics (weight, length, relative bone weight, bone mineral density, bone mineral content, and breaking strength) were not affected (P&gt;0.05) by the usage of halloysite. In conclusion, supplementation of broiler diet with halloysite in the amount of 1% had beneficial effects on the carcass yield and health status of the animals, without any adverse effect on the bone parameters or meat quality of the broiler chickens.

Agarose gel electrophoresis determination of bovine lipoproteins compared with a wet chemistry method

Quantification of serum lipoproteins provides information relative to the overall metabolic health, degree of lipid mobilization, and hepatic function of dairy cattle. Automated assays performed on benchtop chemistry analyzers and commercially available kits use reagents developed for human lipoproteins. The substantial physical and chemical differences between bovine and human lipoproteins potentially confounds the use of these assays in evaluating bovine lipoproteins. In this study, we prospectively analyzed serum lipoproteins from 56 Holstein cows using horizontal slab agarose gel electrophoresis to semi-quantify the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions by optical densitometry. Ultracentrifugation was used to confirm the electrophoretic separation pattern of the lipoproteins. The values obtained using the electrophoretic method were compared with values obtained by direct measure of HDL cholesterol, total cholesterol, and triglyceride (TG) concentrations on a Roche chemistry analyzer, and calculated LDL cholesterol. Correlation between these methods was poor for HDL (Passing-Bablok regression line: y = 30.31 + 0.853x) and could not be calculated for LDL. Automated HDL values were equal to, or higher than, the total cholesterol concentration in 25 of the 56 samples. The TG concentrations were above the reference interval in 18 samples, and these samples had an average of 96% of the cholesterol measured as HDL by the automated method, and 78% HDL by electrophoresis. Given that it is physiologically impossible to have more cholesterol within the HDL fraction than in the total serum fraction, and the increased proportion of TG found in LDL and very-low-density lipoprotein, our results draw into question the accuracy of the Roche automated assay in quantifying bovine lipoprotein fractions.

HYPERLIPIDEMIA AND XANTHOMATOSIS IN YELLOW-FOOTED ROCK WALLABIES (PETROGALE XANTHOPUS) UNDER MANAGED CARE.

Xanthomas are localized lipid deposits in organs with associated granulomatous inflammation. Xanthomatosis is a rare condition in both human and veterinary medicine and is often linked to inherited or acquired dyslipidemias. Three female yellow-footed rock wallabies (Petrogale xanthopus) at a single institution were diagnosed via biopsy with cutaneous xanthomas secondary to hypertriglyceridemia and hypercholesterolemia, and an additional two female yellow-footed rock wallabies were diagnosed with xanthomas at a second institution. All cases presented with cutaneous masses at the haired skin and paw pad junctions of the extremities, and/or mucocutaneous junctions of the face or urogenital tract. The clinically affected individuals were overconditioned or obese, had lipemic serum, and had elevations in blood cholesterol and triglyceride levels. When full lipid panels were performed, inverse high- and low-density lipoprotein fractions were observed. Six other individuals at the first institution had identical husbandry but were of more appropriate body condition, were normolipidemic, and had no xanthomas. One of the affected animals was also concurrently diagnosed with hepatic lipidosis via liver biopsy. Pedigree review and evaluation for underlying endocrine diseases such as hypothyroidism were performed. Because all affected animals were found to be related, a genetic predisposition is possible but requires further investigation. Consideration for the predisposition of some individuals for obesity, hyperlipidemia, and subsequent xanthoma formation should be factored in the husbandry and medical management of this species.

Investigating Causal Relations Between Circulating Metabolites and Alzheimer's Disease: A Mendelian Randomization Study.

Metabolomics is a promising approach that can be used to understand pathophysiological pathways of Alzheimer's disease (AD). However, the causal relationships between metabolism and AD are poorly understood. We aimed to investigate the causal association between circulating metabolites and risk of AD through two-sample Mendelian randomization (MR) approach. Genetic associations with 123 circulating metabolic traits were utilized as exposures. Summary statistics data from International Genomics of Alzheimer's Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD, and 272,244 controls). We utilized inverse-variance weighted method as primary method. We found significantly increased risks of developing AD per standard deviation increase in the levels of circulating ApoB (odd ratio[OR] = 3.18; 95% confidence interval[CI]: 1.52-6.66, p = 0.0022), glycoprotein acetyls (OR = 1.21; 95% CI: 1.05-1.39, p = 0.0093), total cholesterol (OR = 2.73; 95% CI: 1.41-5.30, p = 0.0030), and low-density lipoprotein (LDL) cholesterol (OR = 2.34; 95% CI: 1.53-3.57, p = 0.0001). Whereas glutamine (OR = 0.81; 95% CI: 0.71-0.92, p = 0.0011) were significantly associated with lower risk of AD. We also detected causal effects of several different composition of LDL fractions on increased AD risk, which has been verified in validation. However, we found no association between circulating high-density lipoprotein cholesterol and AD. Our findings suggest causal effects of circulating glycoprotein acetyls, ApoB, LDL cholesterol, and serum total cholesterol on higher risk of AD, whereas glutamine showed the protective effect.

Association between food consumption and high levels of low density lipoprotein cholesterol among obese children.

The increase in the prevalence of obesity and obesity in children is a pattern of the last decades. This public health issue results in metabolic disorders such as dyslipidemia with increased LDL-C. Previous findings shows that most of the Brazilian children does not follow the recommended consumption of fruits and vegetables. To evaluate the association of dietary intake characteristics with elevated serum cholesterol from low density lipoprotein in obese children. Cross-sectional study involving 137 obese children (5-10 years). The mean age of the studied children was 8.27 years, 55.5% were male The weight measurements were performed on a digital anthropometric scale. The body mass index was calculated for each child and the Food Frequency Questionnaire was applied. The peripheral blood was collected for lipid profile analysis. Stata 12.0 statistical package was used to analyze the data, considering a significance level of p < 0.05. The prevalence of hypercholesterolemia based on the serum cholesterol from low density lipoprotein fraction was 14.6%. It was observed that children in the group who consumed the lower difference of risky and protective foods on a daily basis were not less likely to have a high cholesterol from low density lipoprotein level as a criterion for hypercholesterolemia (p = 0.218). A large proportion of the individuals presented levels of lipid profile classified as undesirable for age, as well as food rich in components capable of increasing this profile, which should encourage the intensification in measures of prevention of cardiovascular diseases since childhood.