Plasma Lipid Composition Research Articles

Fatty acid composition of plasma lipids in familial LCAT deficiency supports the formation of ACAT2-derived cholesteryl esters in humans

Background and Aims : Mutations in the LCAT gene cause Familial LCAT Deficiency (FLD,OMIM#245900), a rare metabolic disorder characterized by severe HDL deficiency, hypertriglyceridemia, and an increased unesterified to total cholesterol ratio. Despite the complete lack of LCAT activity, FLD cases have circulating cholesteryl esters (CE), thus representing a tool to analyze the origin of VLDL cholesteryl esters.

A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women

Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.

The Allelic Variant A391T of Metal Ion Transporter ZIP8 (SLC39A8) Leads to Hypotension and Enhanced Insulin Resistance.

The metal ion transporter ZIP8 (SLC39A8) mediates cellular uptake of vital divalent metal ions. Genome-wide association studies (GWAS) showed that the single-nucleotide polymorphism (SNP) variant A391T (rs13107325) is associated with numerous human traits, including reduced arterial blood pressure, increased body mass index and hyperlipidemia. We analyzed in vitro the transport properties of mutant ZIP8 A391T and investigated in vivo in mice the physiological effects of this polymorphism. In vitro, the intrinsic transport properties of mutant ZIP8 were similar to those of wild type ZIP8, but cellular uptake of zinc, cadmium and iron was attenuated due to reduced ZIP8 plasma membrane expression. We then generated the ZIP8 A393T mice (ZIP8KI) that carry the corresponding polymorphism and characterized their phenotype. We observed lower protein expression in lung and kidney membrane extracts in ZIP8KI mice. The ZIP8KI mice exhibited striking changes in metal ion composition of the tissues, including cobalt, palladium, mercury and platinum. In agreement with GWAS, ZIP8KI mice showed reduced arterial blood pressure. Body weight and plasma lipid composition remained unchanged, although these features were reported to be increased in GWAS. ZIP8KI mice also exhibited remarkable insulin resistance and were protected from elevated blood glucose when challenged by dietary sucrose supplementation. We showed that increased hepatic insulin receptor expression and decreased ZnT8 (slc30a8) metal ion transporter mRNA expression are associated with this phenotypic change. In conclusion, our data reveal that ZIP8 plays an important role in blood pressure regulation and glucose homeostasis.

Effect of Massage with Oil Balanced in Essential Fatty Acids on Development and Lipid Parameters in Very Premature Neonates: A Randomized, Controlled Study.

Background: Oil massage versus only massage can increase preterm newborn development, especially weight gain, via a supposed percutaneous absorption of oil lipids, but data are contradictory. Aims: Investigating whether massage with a vegetable oil balanced in essential fatty acids improves neonatal weight gain, and digestive autonomy as proxy for neuro-development outcomes. Methods: A prospective monocentric randomized study was conducted in very premature newborns who received massage with oil (isio4 10 mL/kg/day, n = 18) versus with no oil (n = 18) for five consecutive days (10-min session twice daily) at a corrected gestational age of 34–35 weeks. Anthropometrics and clinical characteristics were recorded. Plasma triglyceride and total cholesterol concentrations were analyzed with an enzymatic kit. The fatty acid composition (weight%, mg/mL) of total plasma lipids and of red blood cell (RBC) membrane was analyzed by gas chromatography. Results: Weight gain velocity at the end of massage period was 12.3 ± 1.4 g/kg/day with oil vs. 9.8 ± 1.4 g/kg/day with no oil (p = 0.1). Digestive autonomy, plasma lipid parameters, polyunsaturated fatty acids in plasma total lipids or in RBC were comparable. The no oil group displayed a higher RBC level in nervonic acid at discharge (4.3 ± 0.2 vs. 3.4 ± 0.2%; p = 0.025) and in C18:1n-9 plasmalogen species at the end of the massage period and at discharge (0.73 ± 0.06 vs. 0.48 ± 0.06; 0.92 ± 0.06 vs. 0.69 ± 0.06%; p < 0.01), two molecules that are involved in neurodevelopment. Conclusions: The use of isio4 oil did not provide additional benefits for the development of very premature newborns, neither changed lipid metabolism nor polyunsaturated fatty acid biological status, which did not corroborate the existence of a percutaneous route for oil lipid absorption. The reason for different levels of nervonic acid and plasmalogen in RBC remains to be explored.

ОЦІНКА ПОКАЗНИКІВ ЛІПІДНОГО ОБМІНУ У ПАЦІЄНТІВ З ІШЕМІЧНОЮ ХВОРОБОЮ СЕРЦЯ ТА ГЕНЕРАЛІЗОВАНИМ ПАРОДОНТИТОМ

Introduction. It has been assumed that generalized periodontitis (GP) adversely affects the qualitative and quantitative composition of plasma lipids and lipoproteins. On the other hand, periodontal treatment and reduction of general periodontal pocket infection in patients with GP are associated with a decrease in total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG). The aim of the study was to conduct a comparative assessment of the state of lipid metabolism in patients with coronary artery disease (CAD) depending on the GP severity. Methods. The study included 101 patients (mean±SD age - 58.2 ± 8.3 years) with CAD and GP, 58 men (57.4%) and 43 women (42.6%). According to the severity of GP, study participants were divided into 3 groups: group I - patients with CAD and GP stage I (initial periodontitis), group II - patients with CAD and GP stage II (moderate periodontitis) and group III - patients with CAD and GP stage III and IV (severe periodontitis). The control group included 9 patients with CAD and clinical gingival health on an intact periodontium (mean±SD age - 56.3 ± 6.1 years), 5 men (55.6%) and 4 women (44.4%). The diagnosis of CAD and the results of lipid metabolism were obtained by analyzing the inpatient medical records. Results. It was revealed that the values of TC, LDL-C, very low-density lipoprotein-cholesterol (VLDL-C), TG and atherogenic coefficient (AC) were lower in the group of patients with CAD and clinical gingival health compared to the level of the corresponding indicators in the groups of patients with CAD and GP (p&lt;0.05). In the analysis of lipid profile in patients with CAD and GP of varying severity, it was found that the average levels of TC, LDL-C, and AC in the subjects of group I were significantly lower compared to the corresponding indicators of groups II and III (p&lt;0.05). There was no statistical difference in the values of lipid metabolism in groups II and III (p&gt;0.05). No significant difference was found in high-density lipoprotein-cholesterol (HDL-C) levels between the comparison groups including the patients with CAD and clinical gingival health (p&gt;0.05), as well as the gender characteristics of the analyzed indicators in the examined patients. Conclusions. Average levels of TC, LDL-C, and AC in patients with CAD and GP increase with increasing destructive-inflammatory changes in periodontal tissues, therefore, with the severity of GP indicating the progression of atherogenesis along with the increased inflammatory process in the periodontium

Relationship of cow and calf circulating lipidomes with colostrum lipid composition and metabolic status of the cow

Newborn calves rely on lipids in colostrum for energy and immune function. The lipid concentration in colostrum, however, is highly variable, and little is known about its composition and maternal factors that influence its composition. The first objective was to measure plasma lipid composition of multiparous cows at 35 d before calving (BC; 35 ± 3 d; ± standard deviation) and 7 d BC (7 ± 2 d), their colostrum, and serum lipid composition of calves (24 h after birth) using multiple reaction monitoring profiling, which is an exploratory and highly sensitive lipidomic analysis method that screens lipids based on chemical functionality. Second, data were analyzed to determine if there were relationships between circulating lipids in the cow, colostrum lipids, and calf serum lipids. Third, relationships between markers of metabolic status of the cows and circulating and colostrum lipids were analyzed with correlation analysis. Blood was sampled and plasma prepared from multiparous cows (n = 16) at 35 and 7 d BC. Within 3 h of parturition, colostrum was collected from cows and fed to her calf. Calves received another feeding of colostrum within 12 h after birth and a serum sample was collected from each calf 24 h after the first feeding of colostrum. The metabolic status of cows was evaluated using insulin, glucose, and nonesterified fatty acid area under the curve in response to an intravenous glucose tolerance test performed at 3 wk BC. Lipids were extracted from plasma, colostrum, and calf serum and were analyzed using multiple reaction monitoring profiling. Concentration of lipids were calculated using spiked in standards and expressed as percent of lipids identified. Data were uploaded into MetaboAnalyst 5.0 for multivariate and univariate analysis. Principal component analysis indicated that circulating lipids in the cow and calf were distinct from lipids in colostrum. Phosphatidylglycerol (PG) concentration was greater in colostrum and calf serum than in cow plasma, with 23 of the 24 PG found in colostrum also found in calf serum. In response to intravenous glucose tolerance test in late gestation, nonesterified fatty acid area under the curve was positively related to total triacylglycerols lipids in 7 d BC plasma (r = 0.63) but negatively related to total membrane lipids in colostrum (r = -0.55). Thus, the metabolic status of the dam influences circulating lipids and colostrum lipid content. Moreover, the circulating lipidome of the cow and calf are similar to one another and distinct from the colostrum lipidome, except for PG, where it appears that colostrum serves as the source for PG in the calf's circulation.

Manipulation of Fatty Acid Metabolism Impairs Megakaryocyte Differentiation and Platelet Production

Background: Obesity is associated with an altered plasma lipid composition that impacts platelet activation, indicating that lipids directly affect platelet function and reactivity. However, very little is known about which essential lipids are important to enable platelet production from their precursors, megakaryocytes (MKs), and whether obesity influences lipid composition and consequently affects thrombopoiesis.Aim: We aimed to determine which lipids and associated pathways play a significant role in MK differentiation and platelet production in health and upon obesity. Our long-term goal is to determine if we can manipulate MK maturation and platelet production through lipid incorporation or inhibition.Methods: In order to determine the lipid profile of MKs through maturation, we performed an extensive lipidomics screen on primary MK progenitors, mature MKs, and platelets. Based on our findings, we then targeted de novo fatty acid (FA) synthesis in MKs to determine whether manipulation of this pathway attenuates MK differentiation and platelet formation. In parallel, we investigated megakaryo- and thrombopoiesis in an experimental setting of diet-induced obesity (DIO) in mice to examinate how altered lipid compositions within the plasma affect MK maturation.Results: Lipidomic data revealed increased polyunsaturated FA and plasmalogen content in the late stages of MKs maturation, suggesting that lipid composition is undergoing changes that may enable platelet production. To validate and extend these results, we inhibited multiple enzymes in de novo lipogenesis and FA synthesis. Using two different sources of primary murine hematopoietic stem cells (HSCs), we found that MK differentiation and maturation from HSCs was significantly decreased up to 60% after inhibition of acetyl-coA carboxylase (ACC) and 80% after fatty acid synthetase (FASN) inhibition, both enzymes from the de novo lipogenesis pathway. Moreover, we also found that MK differentiation and maturation were highly decreased (up to 70%) after the inhibition of acyl-coA synthetase (ACS). To further examine the role of fatty acids incorporation on platelet production, we next treated mature MKs with an ACS inhibitor to investigate the direct effect of FA incorporation on proplatelet formation; we observed a significant, multifoldreduction in proplatelet area. While dihydroceramides were altered in the lipidomic data, impairment of the de novo ceramide synthesis pathway did not affect either MK maturation or platelet production. Moreover, we observed an increased abundance of HSCs, myeloid cells, and MK progenitors in the bone marrow of DIO mice compared to control mice on a chow diet. This further supports an important role for lipids in megakaryopoiesis and suggests that differences in platelet reactivity during obesity may be caused by altered MK maturation and/or platelet production.Conclusions: Our results elucidate an important and previously unrecognized role for fatty acid synthesis in megakaryopoiesis and platelet production. The findings imply that an altered lipid content, as observed in patients with obesity, may not only impact platelet reactivity but also MK maturation and function. Consequently, platelets with an altered lipid content might originate from pathogenic MKs in obesity, which makes lipid-regulating proteins in MKs novel and viable therapeutic targets. DisclosuresMachlus: KEROS Therapeutics: Consultancy, Honoraria; STRM.BIO: Consultancy, Honoraria.

Lipidomic profiling reveals distinct differences in plasma lipid composition in overweight or obese adolescent students

IntroductionThe relationship between dyslipidemia and obesity has been widely reported, but the global lipid profiles associated with the development of obesity still need to be clarified. An investigation into the association between the lipidomic plasma profile and adolescent obesity may provide new insights into the development of obesity.MethodsMass spectrometry coupled with liquid chromatography was applied to detect the global lipidome in the fasting plasma from 90 Chinese adolescents, including 34 obese adolescents, 26 overweight adolescents, and 30 adolescents with a normal body mass index (BMI). All participants underwent anthropometric measurements by using InBody. Clinical biochemical indicators were measured by Cobas Elecsys.ResultsBoth qualitative and quantitative analyses revealed a gradual change in plasma lipid features among obese students, exhibiting characteristics close to overweight students, but differing significantly from normal students. Compared with normal and overweight students, levels of triglyceride (TG), 18-hydroxycortisol, isohumulinone A, and 11-dihydro-12-norneoquassin were up-regulated in the obese group, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC (LPC), lysoPE (LPE), and phosphatidylinositol (PI) were significantly down-regulated in the obese group. Then, we conducted Venn diagrams and selected 8 significant metabolites from the 3 paired comparisons. Most of the selected features were significantly correlated with the anthropometric measurements.ConclusionsThis study demonstrated evidence for a relationship between the eight significant metabolites with obese adolescents. These lipid features may provide a basis for evaluating risk and monitoring the development of obesity.

PSVI-21 Fatty acid composition of blood lipids in lambs of different genotypes in ontogeny

Abstract The early period of postnatal ontogeny of sheep is characterized by a variety of metabolic processes that result in the formation and consolidation of a certain type of metabolism. A special role is played by lipids, which together with proteins and carbohydrates constitute the bulk of organic compounds, cells and the organism as a whole. The purpose of this research was to study the polymorphism of CAST and GH genes as well as its association with the fatty acid composition of blood plasma lipids in lambs. The content of fatty acids was determined by gas-liquid chromatography in the form of methyl esters. From the data obtained, it follows that in all studied ontogeny periods the peripheral blood of sheep with CASTNN and CASTMM genotypes had a higher concentration of fatty acids such as palmitic, stearic, linoleic, and arachidonic acids. The content is as follows: 27.58, 45.40, 3.16, 0.28% vs. 26.21, 45.31, 3.62, 0.18% at the age of 2 months; 25.07, 43.25, 6.05, 1.74% vs. 23.24, 38.76, 6.49, 1.32% at the age of 4 months; 20.64, 22.26, 14.17, 3.38% vs. 17.64, 19.91, 15.07, 2.46% at the age of 8 months (P ˂ 0.05), (P ˂ 0.01). Studies of blood lipid composition of GHBBand GHAA genotype carriers showed that palmitic, stearic, linoleic, and arachidonic acids were dominant: 27.95, 27.96, 19.04% vs. 26.08, 23.88, 17.56% at the age of 2 months, 46.87, 39.87, 22.37% vs. 3.24, 6.87, 15.56% at the age of 4 months; 0.45, 1.68, 3.81% vs. 0.29, 1.29, 3.19% at the age of 8 months (P ˂ 0.05), (P ˂ 0.01). Thus, this study emphasizes that there is a close relationship between the ratio of fatty acids in total blood lipids in lambs and the intensity of growth and development, ensuring and controlling the direction of biochemical processes in the growth and development of young sheep.

Assessment of changes in blood plasma biochemical indices at hypercholesterol diet with a high fat load

Introduction. It was studied the lipid composition of the blood plasma of rats under the impact of a hyper cholesterol diet with a high fat load. It was carried out the prevention of disturbances in blood plasma biochemical parameters with a lipid complex from the tunic of the marine hydrobiont Halocynthia aurantium. Materials and methods. The experiment was carried outwith outbred male rats weighing 200 ± 3 g.The experimental model of a hyper cholesterol diet with a high fat load with the development of dyslipidemia was set up by feeding the animals with ahigh fat diet consisting of 2% cholesterol and 20% beef fat from the total diet. The animals were divided into the following groups of 10 rats each: group 1 - control (standard diet), group 2 - dyslipidemia (hypercholesterol diet with high fat load), group 3 - dyslipidemia + lipid complex from ascidia. Results. It was shown that the influence of the diet was accompanied by an increase in the amount of total lipids in the blood plasma of rats, cholesterol, low-density lipoproteins (LDL), as well as a decrease in total phospholipids and high-density lipoproteins (HDL), which is considered as an indicator of the formation of dyslipidemia. The contents of phospholipid lysofractions increased due to the activation of phospholipases. The amount of fatty acid esters and cholesterol esters decreased, which indicates the inhibition of esterification processes. The imbalance in the phospholipid spectrum of blood plasma occurred: the amount of metabolically active fractions required for the functioning of membrane-bound enzymes decreased. The addition of a lipid complex from the tunic of ascidian purple into the diet was accompanied by a pronounced prophylactic effect, which manifested itself in the normalization of the studied biochemical parameters. The lipid complex containing a wide range of “sea” phospholipids and polynonsaturated fatty acids of the n-3 type is an important basis for application as prophylactic in the conditions of a hypercholesterol diet with a high-fat load. Conclusion. Application of the lipidic complexes containing the “sea” lipids allocated from a tunic of the ascidian purple can be useful and perspective at a dislipidemiya and a hypercholesterolemia that will allow to carry out effective prevention of violations of metabolic reactions at influence of hyper high-calorie food.

Postprandial plasma lipidome responses to a high-fat meal among healthy women

Postprandial lipemia consists of changes in concentrations and composition of plasma lipids after food intake, commonly presented as increased levels of triglyceride-rich lipoproteins. Postprandial hypertriglyceridemia may also affect high-density lipoprotein (HDL) structure and function, resulting in a net decrease in HDL concentrations. Elevated triglycerides (TG) and reduced HDL levels have been positively associated with risk of cardiovascular diseases development. Here, we investigated the plasma lipidome composition of 12 clinically healthy, nonobese and young women in response to an acute high-caloric (1135 kcal) and high-fat (64 g) breakfast meal. For this purpose, we employed a detailed untargeted mass spectrometry-based lipidomic approach and data was obtained at four sampling points: fasting and 1, 3 and 5 h postprandial. Analysis of variance revealed 73 significantly altered lipid species between all sampling points. Nonetheless, two divergent subgroups have emerged at 5 h postprandial as a function of differential plasma lipidome responses, and were thereby designated slow and fast TG metabolizers. Late responses by slow TG metabolizers were associated with increased concentrations of several species of TG and phosphatidylinositol (PI). Lipidomic analysis of lipoprotein fractions at 5 h postprandial revealed higher TG and PI concentrations in HDL from slow relative to fast TG metabolizers, but not in apoB-containing fraction. These data indicate that modulations in HDL lipidome during prolonged postprandial lipemia may potentially impact HDL functions. A comprehensive characterization of plasma lipidome responses to acute metabolic challenges may contribute to a better understanding of diet/lifestyle regulation in the metabolism of lipid and glucose.

Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression.

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain—an index of neuronal damage—were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism—potentially sustained by increased triacylglyceride content—and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.

Plasma and acrosomal membrane lipid content of saltwater crocodile spermatozoa.

This study describes the chemical lipid composition of the sperm plasma and acrosomal membranes of the saltwater crocodile Crocodylus porosus with the aim of providing new insights into sperm physiology, particularly that associated with their preservation ex vivo . The specific fatty acid composition of the sperm plasma and acrosomal membranes is documented. The mean (±s.d.) ratio of unsaturated to saturated membrane fatty acids within the plasma membrane was 2.57±0.50, and was determined to be higher than a similar analysis of the lipids found in the acrosomal membrane (0.70±0.10). The saltwater crocodile sperm plasma membrane also contained remarkably high levels of cholesterol (mean (±s.d.) 40.7±4.5 nmol per 106 sperm cells) compared with the spermatozoa of other amniote species that have so far been documented. We suggest that this high cholesterol content could be conferring stability to the crocodile sperm membrane, allowing it to tolerate extreme osmotic fluxes and rapid changes in temperature. Our descriptive analysis now provides those interested in reptile and comparative sperm physiology an improved baseline database for interpreting biochemical changes associated with preservation pathology (e.g. cold shock and cryoinjury), epididymal sperm maturation and capacitation/acrosome reaction.

Plasma lipidome abnormalities in people with HIV initiating antiretroviral therapy

BackgroundDyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation.MethodsConcentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13).ResultsCompared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)-containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers.ConclusionsHIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes.Trial registrationThis study is registered with Clinicaltrials.gov (NCT00660972). Registered April 16, 2008.

Pulmonary hypertension in patients with hemodynamically significant atherosclerotic lesion of a common carotid artery: new pathophysiological mechanisms of the disease

Background. Pulmonary hypertension (PH) is a severe pathology that often leads a patient to death or disability. Recently, the development of PH associated with activation of the sympathetic nervous system (SNS) has been of interest. Some results obtained in an acute experiment on rats showed that activation of the carotid bodies of one external carotid artery is a sufficient stimulus to increase the tone of pulmonary arteries. Obviously, this effect is mediated by the sympathetic nervous system. However, the long-term effects of unilateral hypoxia of the carotid bodies on the morphofunctional state of the pulmonary arteries are not described in the literature.&#x0D; Aim. Effect assessment of common carotid artery bifurcation region ischemia due to the atherosclerotic process on the pulmonary arteries in patients.&#x0D; Materials and methods. The retrospective study was conducted in the Burdenko Neurosurgical Center and in the National Medical Research Center for Cardiology. A total of 60 case histories were analyzed in detail. All patients underwent Duplex scanning of the brachiocephalic arteries, as well as transthoracic echocardiography. The study included patients with atherosclerotic plaque in the area of the common carotid artery bifurcation on either one side or both. Exclusion criteria consisted of diseases that lead to the development of PH. The relationship between the presence of hemodynamically significant atheroma and the development of PH was evaluated.&#x0D; Results. Patients were divided into two groups those with hemodynamically significant atherosclerotic plaque in the common carotid artery bifurcation region at least on one side (more than 75% of the vascular obstruction) and hemodynamically insignificant atheromas in the common carotid artery bifurcation region on one or both sides (less than 45%). Among patients from the first group, 52.8% of the patients had signs of PH. Among patients from the second group, only 16.7% of the patients had signs of PH. The difference in the frequency of PH occurrence between the two selected groups is statistically significant (p=0.005). There were no differences in red blood cells number, platelets number, glucose concentration and lipid composition of blood plasma.&#x0D; Conclusion. Activation of SNS due to hemodynamically significant atherosclerotic plaque in the area of the bifurcation of the common carotid artery may be an independent mechanism for the development of PH.&#x0D; Key words: pulmonary hypertension, carotid bodies, atherosclerotic plaque, sympathectomy of pulmonary arteries.

Beneficial effects of plant sterols/stanols-containing milk powder on lipid metabolism in hamsters

The effect of plant sterols/stanols-containing milk powder (phytosterol milk powder, PSMP, containing 2.78% phytosterols mixture) on lipid metabolism in hamsters was investigated. One hundred male 7-week-old Golden Syrian hamsters were given free access to regular rodent chow and water for 1 week to acclimatize. Four extremely (10%) over- and underweight hamsters were eliminated. Sixteen hamsters were killed and examined for plasma and liver lipid compositions to establish the baseline. The remaining hamster were randomly divided into 5 groups, each group of hamsters had statistically similar average body weight, but fed with different experimental diets for 4 weeks. All 5 groups of hamsters were fed with high fat, high cholesterol diet containing different ingredients. Regular rodent chow diet was supplemented with 0.5% (w/w) cholesterol and corn/coconut oil mixture (corn oil/coconut oil = 1:1) to raise the final fat content to 15% (w/w) (Group 1 - control group). Group 2 was the positive control (PC) group, which was fed with diet containing 0.72% (w/w) phytosterols (consisted of 75% β-sitosterol and 10% campesterol). Groups 3-5 were the experimental groups, of which 12.95, 25.90 or 64.75% (w/w) PSMP 1x, 2x and 5x PSMP groups) was added to the diet and the phytosterol mixture contents in these diets were 0.36, 0.72 and 1.8% (w/w), respectively. At the end of 4-week feeding period, hamsters were killed and the plasma and hepatic lipid compositions together with the fecal neutral sterol content were determined. No adverse effects of PSMP on growth and health condition in hamsters were found in this experiment. At the highest feeding dose of PSMP (64.75%, w/w), hamsters had the highest body weight gain and the lowest plasma and liver lipid contents. PSMP showed significant effects on lowering the concentrations of plasma total cholesterol and low density lipoprotein cholesterol. It could also lower the atherogenic index (LDL-C/HDL-C), hepatic lipid levels and relative liver weight while raising the fecal cholesterol and phytosterols excretion in the hyperlipidemic hamsters.

Daily mycoprotein consumption for 1 week does not affect insulin sensitivity or glycaemic control but modulates the plasma lipidome in healthy adults: a randomised controlled trial.

Mycoprotein consumption has been shown to improve acute postprandial glycaemic control and decrease circulating cholesterol concentrations. We investigated the impact of incorporating mycoprotein into the diet on insulin sensitivity (IS), glycaemic control and plasma lipoprotein composition. Twenty healthy adults participated in a randomised, parallel-group trial in which they consumed a 7 d fully controlled diet where lunch and dinner contained either meat/fish (control group, CON) or mycoprotein (MYC) as the primary source of dietary protein. Oral glucose tolerance tests were performed pre- and post-intervention, and 24 h continuous blood glucose monitoring was applied throughout. Fasting plasma samples were obtained pre- and post-intervention and were analysed using quantitative, targeted NMR-based metabonomics. There were no changes within or between groups in blood glucose or serum insulin responses, nor in IS or 24 h glycaemic profiles. No differences between groups were found for 171 of the 224 metabonomic targets. Forty-five lipid concentrations of different lipoprotein fractions (VLDL, LDL, intermediate-density lipoprotein and HDL) remained unchanged in CON but showed a coordinated decrease (7-27 %; all P < 0·05) in MYC. Total plasma cholesterol, free cholesterol, LDL-cholesterol, HDL2-cholesterol, DHA and n-3 fatty acids decreased to a larger degree in MYC (14-19 %) compared with CON (3-11 %; P < 0·05). Substituting meat/fish for mycoprotein twice daily for 1 week did not modulate whole-body IS or glycaemic control but resulted in changes to plasma lipid composition, the latter primarily consisting of a coordinated reduction in circulating cholesterol-containing lipoproteins.

Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening.

In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10–15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE) mode (UPLC-QTOF-MSE) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients’ plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.

Differential Metabolic Impact of Natural Food-Grade Emulsifiers Rich in Alpha-Linolenic Acid

Abstract Objectives Dietary synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Conversely, natural emulsifiers such as milk polar lipids (PL) are associated with beneficial metabolic effects. The effects of plant PL remain, however, poorly described. Our objective was to evaluate, using two complimentary rodent models, the impact of nutritional doses of lecithin (≤10%) of vegetal sources alternative to soy on gut microbiota, postprandial lipid metabolism, and the bioavailability of an essential plant lipid, alpha-linolenic acid (ALA). Methods For 5 days, male Swiss mice (n = 60) were fed normolipidic diets (identical ALA content) containing 0, 1, 3 or 10% rapeseed lecithin (RL) or 10% soy lecithin. Following an overnight fast, the mice were force-fed the same oil mix and euthanised after 90 min. As a mechanistic study, male Wistar rats (n = 30) with mesenteric duct cannulation were fed 5 oil mixtures containing 0 to 20% RL. Lymph fractions were collected up to 6 h post-gavage. Plasma and lymph lipid composition was determined using GC-FID, chylomicron (CM) size using light-scattering spectroscopy, and intestinal gene expression and faecal microbiota composition by RT-qPCR. Results In mice, the consumption of lecithin significantly increased levels of faecal Clostridium leptum (P &amp;lt; 0.001), regardless of lecithin origin or dose. The partial replacement of oil with lecithin did not significantly alter plasma total lipids nor the expression of genes of intestinal lipid absorption. The percentage of ALA in plasma triglycerides was significantly higher in the 10% RL group compared to other groups (P &amp;lt; 0.05). In rats, RL significantly and dose-dependently increased the rate of appearance (P &amp;lt; 0.01) and concentration of ALA in lymph (P &amp;lt; 0.01). 20% RL additionally increased CM size and expression of genes of CM secretion (Mttp, Sar1b; P &amp;lt; 0.05). Conclusions Our results reveal that, whereas both rapeseed and soy lecithin improved gut microbiota composition by increasing the anti-inflammatory Clostridium leptum bacterial group, only rapeseed lecithin enhanced ALA bioavailability. This study illustrates the importance of considering the use of natural emulsifiers, especially rapeseed lecithin, as plant-based food ingredients with potential health benefits. Funding Sources ANRT and UMT ACTIA BALI.

LIPA gene mutations affect the composition of lipoproteins: Enrichment in ACAT-derived cholesteryl esters

Background and aimsCholesteryl ester storage disease (CESD) due to LIPA gene mutations is characterized by hepatic steatosis, hypercholesterolemia and hypoalphalipoproteinemia, exposing affected patients to an increased cardiovascular risk. Further insights into the impact of LIPA gene mutations on lipid/lipoprotein metabolism are limited. Aim of the study was to investigate the effect of carrying one or two mutant LIPA alleles on lipoprotein composition and function. MethodsLipoproteins were isolated from 6 adult CESD patients, 5 relatives carrying one mutant LIPA allele (carriers) and 12 sex/age matched controls. Lipid profile, lipoprotein mass composition and the fatty acid distribution of cholesteryl esters (CEs) were assessed. HDL function was evaluated as the ability to promote nitric oxide release by endothelial cells. ResultsDespite the lipid-lowering therapy, total cholesterol, LDL-cholesterol and triglycerides were increased in CESD patients compared to controls, while HDL-cholesterol was reduced. Carriers also displayed elevated total and LDL-cholesterol. Very low and intermediate density lipoproteins from CESD patients and carriers were enriched in CEs compared to the control ones, with a concomitant reduction of triglycerides. Fatty acid composition of CEs in serum and lipoproteins showed a depletion of linoleate content in CESD patients, due to the reduced LCAT activity. In CESD HDL, fatty acid distribution of CEs was shifted towards saturated ones, if compared to control HDL. The changes in HDL composition did not affect HDL ability to promote nitric oxide release by endothelial cells. ConclusionsLIPA gene mutations significantly affected plasma levels and lipid composition of lipoproteins, likely contributing to the increased cardiovascular risk of affected patients.