Detailed Lipid Profiles Research Articles

Lipid profile and risk factors for neoatherosclerosis after drug-eluting stent implantation in acute coronary syndrome

Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer.

For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients.

Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry

Spatial omics technologies can reveal the molecular intricacy of the brain. While mass spectrometry imaging (MSI) provides spatial localization of compounds, comprehensive biochemical profiling at a brain-wide scale in three dimensions by MSI with single-cell resolution has not been achieved. We demonstrate complementary brain-wide and single-cell biochemical mapping using MEISTER, an integrative experimental and computational mass spectrometry (MS) framework. Our framework integrates a deep-learning-based reconstruction that accelerates high-mass-resolving MS by 15-fold, multimodal registration creating three-dimensional (3D) molecular distributions and a data integration method fitting cell-specific mass spectra to 3D datasets. We imaged detailed lipid profiles in tissues with millions of pixels and in large single-cell populations acquired from the rat brain. We identified region-specific lipid contents and cell-specific localizations of lipids depending on both cell subpopulations and anatomical origins of the cells. Our workflow establishes a blueprint for future development of multiscale technologies for biochemical characterization of the brain.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Novel lipidomes profile and clinical phenotype identified in pneumoconiosis patients

BackgroundPneumoconiosis is a group of occupational lung diseases caused by the inhalation of mineral dust in the lungs, leading to lung dysfunction. Patients with pneumoconiosis are usually accompanied by weight loss, which suggests a lipid metabolism disorder. Recent progress in lipidomics uncovered detailed lipid profiles that play important roles in respiratory diseases, such as asthma, lung cancer and lung injury. The purpose of this study was to shed light on the different expression of lipidome between pneumoconiosis and healthy, hoping to bring new ideas for the diagnosis and treatment of pneumoconiosis.MethodologyThis non-matching case–control study was performed among 96 subjects (48 outpatients with male pneumoconiosis and 48 healthy volunteers), data of clinical phenotypes were recorded, and plasma biochemistry (lipidomic profiles) was tested for both pneumoconiosis patients and healthy controls. A total of 426 species in 11 lipid classes were analyzed by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS) for the cases and controls. We also analyzed the correlation of lipid profiles with clinical phenomes from pneumoconiosis patients by expression quantitative trait locus (eQTL) model to evaluate trans-nodules between lipidomic profiles and clinical phenomes. All visually re-checked data were analyzed using appropriate statistical tools (t-test or one-way ANOVA test) on SPSS.ResultsCompared with healthy people, 26 significantly increased (> 1.5-fold) and 30 decreased lipid elements (< 2/threefold) in patients with pneumoconiosis were identified (P values all < 0.05). The majority of those elevated lipid elements were phosphatidylethanolamines (PEs), and the minority were free fatty acids (FFAs), while phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) declined in pneumoconiosis. Clinical trans-omics analyses demonstrated that phenomes in pneumoconiosis connections with multiple lipids, which showed that pH, lung function, mediastinal lymph node calcification, and complication were highly correlated with lipid elements. Furthermore, up-regulated PE was corresponded to pH, smoking history and mediastinal lymph node calcification. PC was corresponded to dust exposure history, BMI and mediastinal lymph node calcification.ConclusionWe found altered lipid panels between male pneumoconiosis patients and healthy people by qualitatively and quantitatively measured plasma lipidomic profiles. The trans-omic analysis between clinical phenomes and lipidomes might have the potential to uncover the heterogeneity of lipid metabolism of pneumoconiosis patients and to screen out clinically significant phenome-based lipid panels.

Inflammatory markers in lean Polycystic Ovary Syndrome subjects are not associated with the spectrum of dyslipidemia

HIGHLIGHTS 1. Polycystic ovarian syndrome (PCOS) might be a condition of chronic low degree inflammation and dyslipidemia.2. Association between inflammation markers and dyslipidemia in PCOS patients was investigated.3. Dyslipidemia and chronic low degree inflammation were present in lean PCOS patients, but inflammation markers related insignificantly with dyslipidemia. ABSTRACT Objectives: This study aimed to address the detailed lipid profile in lean woman with PCOS and investigate the relationship between chronic low grade inflammation (using NLR, PLR, and monocyte/HDL ratio) and dyslipidemia (defined as total cholesterol level &gt; 190 mg/dL). Materials and Methods: This study was a cross-sectional study conducted from June – December 2020 at the Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, involving 45 women aged 18 – 35 years old, diagnosed as having PCOS with normal BMI (18.5 – 22.9 kg/m2). To compare quantitative variables, data analysis was carried out using the t-test or Mann-Whitney U test as appropriate; whereas, to compare categorical variables, the Chi-square test was used. Results: We found that although the median BMI was within normal limits at 21.48 kg/m2, the mean values of the lipid profiles were found to be either abnormal or borderline, indicating the high possibility of dyslipidemia. No statistically association between NLR, PLR and MHR with dyslipidemia. Conclusion: Dyslipidemia and chronic low-grade inflammation were found in lean PCOS subjects, but there was no significant association between inflammation markers (NLR, PLR and MHR) and dyslipidemia. Further studies should investigate other factors that cause the inflammation.

Impact of small dense low-density lipoprotein cholesterol and triglyceride-rich lipoproteins on plaque rupture with ST-segment elevation myocardial infarction

Plaque rupture (PR), characterized by a disruption of the fibrous cap of lipid-rich plaques, is the major etiology of ST-segment elevation myocardial infarction (STEMI). Dyslipidemia is a well-known risk factor for PR. Nonetheless, the impact of detailed atherogenic lipid profiles, including small dense low-density lipoprotein cholesterol (sd-LDL-C) and triglyceride-rich lipoproteins (TRLs), on PR has not yet been investigated. To elucidate the impact of sd-LDL-C and TRL levels on PR in patients with STEMI using optical coherence tomography (OCT). A total of 106 consecutive statin-naive patients with STEMI were enrolled. The PR in culprit lesions was assessed on pre-intervention OCT images, and serum samples were collected immediately before coronary angiography. Sd-LDL-C was directly measured using a homogeneous assay. TRL-cholesterol (TRL-C) was estimated by subtracting the LDL-C level from the non-high-density lipoprotein cholesterol level. Clinical characteristics and lipid profiles were compared between the PR and intact fibrous cap (IFC). No difference in LDL-C levels was observed between the PR (n=64) and IFC (n=42) groups (120.0 mg/dL vs. 129.5 mg/dL, p=0.97); however, sd-LDL-C levels were significantly higher in the PR group (38.9 mg/dL vs. 32.4 mg/dL, p=0.04). Similarly, the PR group had higher TRL-C (24.0 mg/dL vs. 18.0 mg/dL, p=0.01) and triglyceride (130.0 mg/dL vs. 100.3 mg/dL, p=0.03) levels than the IFC group.Multivariate logistic regression analysis showed that sd-LDL-C was an independent factor determining PR (odds ratio, 1.53 per 10 mg/dL; p=0.04). Only sd-LDL-C levels were significantly associated with PR in culprit lesions in patients with STEMI.

Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China.

Background: Clinical data on the correlation of dyslipidaemia with the long-term outcomes of ulcerative colitis (UC) are limited. This study aimed to evaluate the impact of lipid levels on disease activity and prognosis in UC. Methods: The retrospective data of UC patients who had detailed lipid profiles were collected from January 2003 to September 2020. All patients were followed-up to 30 September 2021. The long-term outcomes were UC-related surgery and tumorigenesis. Results: In total, 497 patients were included in the analysis. Compared to patients with normal lipid levels, those with dyslipidaemia commonly presented with more serious disease activity. Low high-density lipoprotein cholesterol (p < 0.05) levels were associated with higher risks of severe disease activity in UC. Regarding the long-term outcomes, patients with persistent dyslipidaemia were at higher risks of UC-related surgery (HR: 3.27, 95% CI: 1.86–5.75, p < 0.001) and tumorigenesis (HR: 7.92, 95% CI: 3.97–15.78, p < 0.001) and had shorter surgery- and tumour-free survival (p < 0.001) than patients with transient dyslipidaemia and normal lipid levels. Low levels of high-density lipoprotein cholesterol (p < 0.001) and apolipoprotein A1 (p < 0.05) were associated with higher risks of surgery and tumorigenesis. Conclusion: Persistent dyslipidaemia was associated with a higher risk of serious disease activity and worse long-term outcomes among patients with UC. Lipid patterns should be assessed to improve the management of high-risk patients with UC in the early phase.

Optimizing accelerated solvent extraction combined with liquid chromatography-Orbitrap mass spectrometry for efficient lipid profile characterization of mozzarella cheese

In this study, a novel Accelerated Solvent Extraction (ASE) procedure combined with UHPLC-Q-Orbitrap-MS was developed for detailed untargeted lipid profile of mozzarella cheese. Response Surface Methodology and Pareto front, using a Central Composite Design (CCD), were employed to define the optimised combination of extraction temperature, number of extraction cycles and mix of solvents. LipidSearch™ software was used for a reliable and accurate lipid identification. A total of 13 subclasses, including ceramides, diacylglycerols, triacylglycerols, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, sphingomyelins, bismethyl phosphatidic acids, cholesterol ester, zymosterol ester, hexosyl ceramides were measured. The elaboration of the CCD showed that the solvents ratio was the main factor affecting the extraction efficiency. The optimised ASE method, together with the Folch extraction, synergistically contributed to a complete characterization of lipid profile of mozzarella cheese, confirming ASE technique, associated with high resolution mass spectrometry detection, as an efficient tool for Lipidomics in food science.

Lipidome in-depth characterization highlights the nutritional value and species-specific idiosyncrasies of different Ulva species

The genus Ulva comprises a large number of species widespread in the world, several of which are of commercial value, mainly for their nutritional benefits. However, identifying Ulva species is notoriously difficult, which largely explains why very few studies have attempted to characterize physiological and nutritional differences within the genus. If environmental modulation of seaweed lipid biomass composition for a number of species is well-documented, much less is known about genetic-driven differences in lipid profiles within a species or a genus. In this study, we analyzed the lipid profile of strains belonging to three species of foliose Ulva grown in the same conditions. Fatty acid profiling revealed the presence of 25 different fatty acids, palmitic acid being the most abundant fatty acid (FA) present in all species (35.1–41.2%). Important differences between the three species studied (U. australis, U. lacinulata and U. rigida) were observed. U. lacinulata had a higher content of saturated FA and a lower content of n-3 FA, suggesting that U. australis and U. rigida have a higher nutritional value. In contrast, Ulva lacinulata exhibited the lowest n-6/n-3 ratio, an increasingly important nutritional parameter, at the expense of decreased contents in both n-6 and n-3 FAs. A comprehensive analysis of the polar lipidome showed differences in the composition of complex lipids. Major differences were found within the class of sulfolipids, which are specific to chloroplast membranes, and have been proposed as bioactive lipids. Ulva rigida contained high relative amounts of SQDG(32:2) and SQDG(36:5), although a low content of SQMG (16:0), which are sulfolipid species that have been described as having biological activity. Therefore, detailed lipid profiling highlighted inter-specific differences, contributing to a better understanding of the physiology of the species studied, while also highlighting their potential as sources of molecular lipid species with bioactivity and nutritional benefits.

Blood Plasma Metabolites in Diabetes-Associated Chronic Kidney Disease: A Focus on Lipid Profiles and Cardiovascular Risk.

BackgroundWe investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early and late stage diabetes associated chronic kidney disease (CKD), inclusive of stages 1–5 CKD, to identify potential metabolomic profiles between the two groups.MethodsThis cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 57 urine samples using a high-throughput proton Nuclear Magnetic Resonance platform. Analyses were conducted using R with the ggforestplot package. Linear regression models were minimally adjusted for age, sex, and body mass index and p-values were adjusted for multiple comparisons using the Benjamini-Hockberg method with a false discovery rate of 0.05.ResultsApolipoprotein A1 concentration (ApoA1) was reduced (adj. p = 0.04) and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) was increased (adj. p = 0.04) in late CKD compared with early CKD. Low-density lipoprotein triglyceride (LDL-TG) had an increased concentration (adj. p = 0.01), while concentrations of high-density lipoprotein cholesterol (HDL-C) were reduced (adj. p = 0.04) in late CKD compared to early stages of disease.ConclusionOur results highlight the presence of abnormal lipid metabolism namely significant reduction in the protective ApoA1 and significant increase in atherogenic ApoB/ApoA1 ratio. The study also demonstrates significantly elevated levels of triglyceride-rich lipoproteins such as LDL-TG. We illustrate the significant reduction in protective HDL-C in individuals with diabetic CKD. It explores a detailed plasma lipid profile that significantly differentiates between the late and early CKD groups as well as each CKD stage. The study of complex metabolite profiles may provide additional data required to enable more specific cardiovascular risk stratification.

Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients: A propensity score-matched analysis.

Background/AimsTenofovir alafenamide (TAF) has shown less favorable effect on lipids compared to tenofovir disoproxil fumarate (TDF) in clinical trials. However, data regarding these outcomes in patients with chronic hepatitis B (CHB) are scarce. Therefore, this study aimed to evaluate the effect of TAF on the lipid in patients with CHB.MethodsA total of 237 TAF-treated CHB patients compared with TDF, inactive CHB, and non-hepatitis B virus (HBV)-infected control groups using propensity score matching (PSM).ResultsFollowing PSM, each analysis was conducted on cohorts via the matching of 70:140 (TAF:TDF), 89:89 (TAF:inactive CHB), 140:560 (TAF:non-HBV infected control), and 368:1,472 (TDF:non-HBV-infected control). A significant decrease in the total cholesterol (TC) level was noted at 48 weeks in the TDF group compared to the TAF group (176.3±32.9 vs. 156.7±27.7, P<0.001) and the non-HBV-infected control group (175.0±29.5 vs. 156.2±28.3, P<0.001). However, no significant change in TC was observed in the TAF group and inactive CHB or non-HBV-infected control groups at 48 weeks. For the subgroup analyses of TAF vs. non-HBV-infected control subjects and inactive CHB patients whose detailed lipid profile information were available, no between-group differences in TC, low-density lipoprotein (LDL)-cholesterol, highdensity lipoprotein (HDL)-cholesterol, TC/HDL ratio, and LDL/HDL ratio were observed at 48 weeks.ConclusionsTDF seems to have a lipid-lowering effect compared to the non-HBV-infected control and TAF-treated groups. However, in real practice, TAF might not worsen the lipid profiles of subjects compared to non-HBV-infected controls and patients with inactive CHB.

MO455LIPID PROFILE AND UREMIC RETENTION SOLUTES IN PATIENTS WITH END-STAGE KIDNEY DISEASE

Abstract Background and Aims Patients with end-stage kidney disease (ESKD) have an extremely high incidence of cardiovascular (CV) diseases, partly driven by insufficient clearance of uremic toxins. ESKD patients have a characteristically adverse lipid profile, however data investigating the relationship between uremic toxins and lipid profile, potentially contributing to increased CV risk, is scarce. To determine if uremic retention solutes (URS) associate with an adverse lipid profile in ESKD, we studied a large, trinational cohort with a detailed lipid profile, as well as a comprehensive panel of uremic toxins. Method Total, high density lipoprotein (HDL), non-HDL, low density lipoprotein (LDL), and remnant cholesterol, as well as triglyceride, levels were associated with a panel of 15 uremic retention solutes in a combined cohort of 591 European, adult patients with advanced chronic kidney disease (CKD) from UZ Leuven, Belgium (n=150), Karolinska Hospital, Stockholm, Sweden (n=235) or University of Leipzig Medical Center, Leipzig, Germany (n=226). Total and HDL cholesterol, as well as triglycerides, were quantified at each study center, whereas non-HDL cholesterol, LDL cholesterol, and remnant cholesterol were calculated. In all subjects of this trinational study, a selected panel of solutes, including CMPF, TMAO, aromatic amino acids and corresponding end-products of endogenous and microbial metabolism, was centrally quantified in a single lab by liquid chromatography - tandem mass spectrometry. Univariate correlations were assessed using non-parametric Spearman’s rank correlation method. To identify independent associations between solutes and lipid profile, multivariate linear regression models were used with adjustment for age, sex, as well as markers of inflammation, protein energy wasting, renal function, diabetes and dialysis. Results In total, 189 patients in CKD stage 3-5 not on renal replacement therapy (RRT), as well as 402 subjects on RRT, were included. All URS except phenylalanine significantly differed between patients on RRT vs. not on RTT. In univariate analyses, URS negatively correlated with most lipid markers, including LDL and HDL cholesterol. In contrast, the amino acids tryptophan, phenylalanine, and tyrosine were positively correlated with a large majority of lipid markers. After combining URS concentrations based on molecule size, similar associations were observed for the respective groups, i.e. small water-soluble molecules, protein-bound molecules, and amino acids. After adjustment for age, sex, presence of diabetes, dialysis treatment, inflammation, protein energy wasting, and renal function, significant associations were lost for URS and total cholesterol or HDL cholesterol, excluding total cholesterol and phenylacetyl glutamine. However, high triglyceride levels were independently predicted by p-cresyl sulphate, tryptophan, indole-3 acetic acid, phenylalanine, TMAO, small water-soluble molecules combined, and protein-bound molecules combined. Non-HDL cholesterol was independently predicted by phenyl glucuronide, TMAO, phenylacetyl glutamine and small water-soluble molecules combined, while remnant cholesterol was independently associated with 10 out of the 15 URS, as well as small water-soluble molecules combined and amino acids combined. Furthermore, LDL cholesterol independently associated with tryptophan, TMAO, phenylacetyl glutamine and protein-bound molecules combined. Conclusion Significant inverse associations between lipid profile and small water-soluble or protein-bound uremic toxins in advanced CKD highlight the complexity of the uremic environment. Our data suggest that not all URS interactions with conventional CV risk markers may be pathogenic.

Traffic Analysis Reveals the Impact of Dietary Intake on Lipid Metabolism

Plasma-plasma comparisons are the mainstay of investigations of the molecular origins of disease. However, a variety of conditions and phenotypes, including most metabolic disease, arise because of system-wide changes. It is not possible to characterise these from the molecular composition of the circulation alone. We therefore devised a novel analytical approach to be able to understand system-wide changes in molecular metabolism. The computational tool we have developed is called Lipid Traffic Analysis (LTA). This was used to test the hypothesis that altered paternal diet programmed the lipid metabolism in offspring. Detailed lipid profiles were acquired from serum, liver, brain, heart and abdominal adipose tissues from F1 neonate (3 weeks), F1 adult (16 weeks) and F2 neonate offspring. LTA characterised the number, type and abundance of lipid variables in and between tissues, finding a variety of reprogrammings associated with a high carbohydrate paternal diet. These results are important because they describe the long-term metabolic result of parental dietary intake not ascribed to mothers. The novel analytical tool used is important because it offers unparalleled insight into possible mechanisms for alterations in lipid metabolism throughout organisms. We are currently using Lipid Traffic Analysis to answer questions about changes to lipid metabolism in maternally-driven nutritional programming in mice and diet-driven changes in both lipid and sterol metabolism in honeybees.

Lipid Traffic Analysis reveals the impact of high paternal carbohydrate intake on offsprings\u2019 lipid metabolism

In this paper we present an investigation of parental-diet-driven metabolic programming in offspring using a novel computational network analysis tool. The impact of high paternal carbohydrate intake on offsprings’ phospholipid and triglyceride metabolism in F1 and F2 generations is described. Detailed lipid profiles were acquired from F1 neonate (3 weeks), F1 adult (16 weeks) and F2 neonate offspring in serum, liver, brain, heart and abdominal adipose tissues by MS and NMR. Using a purpose-built computational tool for analysing both phospholipid and fat metabolism as a network, we characterised the number, type and abundance of lipid variables in and between tissues (Lipid Traffic Analysis), finding a variety of reprogrammings associated with paternal diet. These results are important because they describe the long-term metabolic result of dietary intake by fathers. This analytical approach is important because it offers unparalleled insight into possible mechanisms for alterations in lipid metabolism throughout organisms.

Three-dimensional (3D) imaging of lipids in skin tissues with infrared matrix-assisted laser desorption electrospray ionization (MALDESI) mass spectrometry.

Three-dimensional (3D) mass spectrometry imaging (MSI) has become a growing frontier as it has the potential to provide a 3D representation of analytes in a label-free, untargeted, and chemically specific manner. The most common 3D MSI is accomplished by the reconstruction of 2D MSI from serial cryosections; however, this presents significant challenges in image alignment and registration. An alternative method would be to sequentially image a sample by consecutive ablation events to create a 3D image. In this study, we describe the use of infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) in ablation-based 3D MSI for analyses of lipids within fresh frozen skin tissue. Depth resolution using different laser energy levels was explored with a confocal laser scanning microscope to establish the imaging parameters for skin. The lowest and highest laser energy level resulted in a depth resolution of 7μm and 18μm, respectively. A total of 594 lipids were putatively detected and detailed lipid profiles across different skin layers were revealed in a 56-layer 3D imaging experiment. Correlated with histological information, the skin structure was characterized with differential lipid distributions with a lateral resolution of 50μm and a z resolution of 7μm.

Fat Distribution and Lipid Profile of Young Adults with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Enzyme Deficiency.

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case-control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18-31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m2 , p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m2 , p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m2 , p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m2 , p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m2 , p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m2 , p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = -0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.

Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells.

SummaryThe role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

Pulmonary Function Test in Patients with Type 2 Diabetes Mellitus &amp; Its Correlation with Anthropometry and Glycemic Control

Background: Diabetes mellitus is a chronic disease with microvascular complications and affecting almost all organs in the body. Effect of diabetes on lung functions has been studied previously with variable results. This study was performed to see the lung functions in patients with type 2 DM and to assess the pattern of abnormality in lung functions.Aim &amp; Objective:Our study aimed to evaluate pulmonary functions in patients with type 2 diabetes mellitus (T2DM) and to determine their correlations with anthropometric profile, glycaemic control, and diabetic microangiopathic complications.Subjects and Methods: 70 T2DM patients and 70 healthy control subjects were taken for the study. After taking an informed consent, all underwent screening with detailed history, anthropometry, blood sugar (fasting and post Prandial), glycosylated haemoglobin (HbA1C), renal profile, lipid profile and Pulmonary functions (spirometry).Statistical Analysis:Student’s t-test was used to compare PFTs of diabetic and control groups. Frequencies were generated for categorical variables and compared using the chi square test.Results: There was significant reduction in all PFT parameters (PEFR (L/s), FEV1 %, FVC ) in diabetics as compared to controls. The FEV1/FVC% was higher in the diabetes group and there was a mixed restrictive and obstructive pattern of pulmonary dysfunction seen in diabetics.BMI was inversely related to PEFR, FEV1, and FVC. Age was inversely related to FEV1, and FVC. It was found that HbA1c was not significant for any ventilator (spirometric) index.Restrictive pattern rather than obstructive impairment of lung function is likely to be chronic complication of T2DM, the severity of which relates to longer duration of symptoms of diabetes, higher BMI, and advancing age.Conclusion: Spirometry is an easily available, non invasive screening tool to assess the lung functions and should be performed in patients with type 2 diabetes having microangiopathic complications.

Small Dense Low-Density Lipoprotein Cholesterol Predicts Cardiovascular Events in Liver Transplant Recipients.

Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Although LT is associated with dyslipidemia, particularly atherogenic lipoprotein subparticles, the impact of these subparticles on CVD-related events is unknown. Therefore, the aim of the current study was to evaluate the impact of small dense (sdLDL-C) low-density lipoprotein (LDL) cholesterol (LDL-C) on CVD events. Prospectively enrolled patients (N = 130) had detailed lipid profile consisting of traditional lipid parameters and sdLDL-C and were followed for CVD events. The primary endpoint was a CVD composite consisting of myocardial infarction (MI), angina, need for coronary revascularization, and cardiac death. Mean age of the cohort was 58±11 years, and the most common etiology of liver disease (LD) was hepatitis C virus (N = 48) and nonalcoholic steatohepatitis (N = 23). A total of 20 CVD events were noted after median follow-up of 45 months. The baseline traditional profile was similar in patients with and without CVD events. A serum LDL-C cutoff of 100 mg/dL was unable to identify individuals at risk of a CVD event (P = 0.86). In contrast, serum concentration of atherogenic sdLDL-C >25 mg/dL was predictive of CVD events with a hazard ratio of 6.376 (95% confidence interval, 2.65, 15.34; P < 0.001). This relationship was independent of diabetes, hypertension, sex, ethnicity, LD, obesity, and statin use. Conclusion: sdLDL-C independently predicted CVD events whereas LDL-C did not. Thus, sdLDL-C may provide a useful clinical tool in risk stratifying and managing patients after LT.