Untargeted lipidomic analysis of plasma from obese women submitted to combined physical exercise.
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ABSTRACT:
SUBMITTER: San Martin R
PROVIDER: S-EPMC9263166 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Exercise and physical activity levels influence myokine release from skeletal muscle and contribute to circulating concentrations. Indeed, many myokines, including interleukin (IL)-6, IL-15, secreted protein acidic rich in cysteine (SPARC), and fibroblast growth factor (FGF) 21 are higher in the circulation after an exercise bout. Since these peptides modulate muscle metabolism and can also be targeted toward other tissues to induce adaptations to energy demand, they are of great interest regarding metabolic diseases. Therefore, we set out to compare, in six women with obesity (BMI ≥30 kg/m2) and five healthy women (BMI 22-29.9 kg/m2), the effect of an acute bout of moderate-intensity, continuous cycling exercise (60 min, 60% VO2peak) on the release of myokines (IL-6, IL-8, IL-10, IL-13, IL-15, SPARC, and FGF21) in plasma for a 24-h time course. We found that plasma IL-8 and SPARC levels were reduced in the group of women with obesity, whereas plasma IL-13 concentrations were elevated in comparison to non-obese women both before and after the exercise bout. We also found that plasma FGF21 concentration during the 24 h following the bout of exercise was regulated differently in the non-obese in comparison to obese women. Plasma concentrations of FGF21, IL-6, IL-8, IL-15, and IL-18 were regulated by acute exercise. Our results confirm the results of others concerning exercise regulation of circulating myokines while providing insight into the time course of myokine release in circulation after an acute exercise bout and the differences in circulating myokines after exercise in women with or without obesity.
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Project description:The goal of this work was to develop a label-free, comprehensive, and reproducible high-resolution liquid chromatography-mass spectrometry (LC-MS)-based untargeted lipidomic workflow using a single instrument, which could be applied to biomarker discovery in both basic and clinical studies. For this, we have (i) optimized lipid extraction and elution to enhance coverage of polar and nonpolar lipids as well as resolution of their isomers, (ii) ensured MS signal reproducibility and linearity, and (iii) developed a bioinformatic pipeline to correct remaining biases. Workflow validation is reported for 48 replicates of a single human plasma sample: 1124 reproducible LC-MS signals were extracted (median signal intensity RSD = 10%), 50% of which are redundant due to adducts, dimers, in-source fragmentation, contaminations, or positive and negative ion duplicates. From the resulting 578 unique compounds, 428 lipids were identified by MS/MS, including acyl chain composition, of which 394 had RSD < 30% inside their linear intensity range, thereby enabling robust semiquantitation. MS signal intensity spanned 4 orders of magnitude, covering 16 lipid subclasses. Finally, the power of our workflow is illustrated by a proof-of-concept study in which 100 samples from healthy human subjects were analyzed and the data set was investigated using three different statistical testing strategies in order to compare their capacity in identifying the impact of sex and age on circulating lipids.
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Project description:Polycystic ovary syndrome (PCOS) is a common disorder affecting between 5 and 18 % of females of reproductive age and can be diagnosed based on a combination of clinical, ultrasound and biochemical features, none of which on its own is diagnostic. A lipidomic approach using liquid chromatography coupled with accurate mass high-resolution mass-spectrometry (LC-HRMS) was used to investigate if there were any differences in plasma lipidomic profiles in women with PCOS compared with control women at different stages of menstrual cycle. Plasma samples from 40 women with PCOS and 40 controls aged between 18 and 40 years were analysed in combination with multivariate statistical analyses. Multivariate data analysis (LASSO regression and OPLS-DA) of the sample lipidomics datasets showed a weak prediction model for PCOS versus control samples from the follicular and mid-cycle phases of the menstrual cycle, but a stronger model (specificity 85 % and sensitivity 95 %) for PCOS versus the luteal phase menstrual cycle controls. The PCOS vs luteal phase model showed increased levels of plasma triglycerides and sphingomyelins and decreased levels of lysophosphatidylcholines and phosphatidylethanolamines in PCOS women compared with controls. Lipid biomarkers of PCOS were tentatively identified which may be useful in distinguishing PCOS from controls especially when performed during the menstrual cycle luteal phase.
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Project description:As part of the Community Structure-Activity Resource (CSAR) center, a set of 343 high-quality, protein-ligand crystal structures were assembled with experimentally determined K(d) or K(i) information from the literature. We encouraged the community to score the crystallographic poses of the complexes by any method of their choice. The goal of the exercise was to (1) evaluate the current ability of the field to predict activity from structure and (2) investigate the properties of the complexes and methods that appear to hinder scoring. A total of 19 different methods were submitted with numerous parameter variations for a total of 64 sets of scores from 16 participating groups. Linear regression and nonparametric tests were used to correlate scores to the experimental values. Correlation to experiment for the various methods ranged R(2) = 0.58-0.12, Spearman ρ = 0.74-0.37, Kendall τ = 0.55-0.25, and median unsigned error = 1.00-1.68 pK(d) units. All types of scoring functions-force field based, knowledge based, and empirical-had examples with high and low correlation, showing no bias/advantage for any particular approach. The data across all the participants were combined to identify 63 complexes that were poorly scored across the majority of the scoring methods and 123 complexes that were scored well across the majority. The two sets were compared using a Wilcoxon rank-sum test to assess any significant difference in the distributions of >400 physicochemical properties of the ligands and the proteins. Poorly scored complexes were found to have ligands that were the same size as those in well-scored complexes, but hydrogen bonding and torsional strain were significantly different. These comparisons point to a need for CSAR to develop data sets of congeneric series with a range of hydrogen-bonding and hydrophobic characteristics and a range of rotatable bonds.
| S-EPMC3186041 | biostudies-literature
Project description:RationaleThe Lipidyzer platform was recently updated on a SCIEX QTRAP 6500+ mass spectrometer and offers a targeted lipidomics assay including 1150 different lipids. We evaluated this targeted approach using human plasma samples and compared the results against a global untargeted lipidomics method using a high-resolution Q Exactive HF Orbitrap mass spectrometer.MethodsLipids from human plasma samples (N = 5) were extracted using a modified Bligh-Dyer approach. A global untargeted analysis was performed using a Thermo Orbitrap Q Exactive HF mass spectrometer, followed by data analysis using Progenesis QI software. Multiple reaction monitoring (MRM)-based targeted analysis was performed using a QTRAP 6500+ mass spectrometer, followed by data analysis using SCIEX OS software. The samples were injected on three separate days to assess reproducibility for both approaches.ResultsOverall, 465 lipids were identified from 11 lipid classes in both approaches, of which 159 were similar between the methods, 168 lipids were unique to the MRM approach, and 138 lipids were unique to the untargeted approach. Phosphatidylcholine and phosphatidylethanolamine species were the most commonly identified using the untargeted approach, while triacylglycerol species were the most commonly identified using the targeted MRM approach. The targeted MRM approach had more consistent relative abundances across the three days than the untargeted approach. Overall, the coefficient of variation for inter-day comparisons across all lipid classes was ∼ 23% for the untargeted approach and ∼ 9% for the targeted MRM approach.ConclusionsThe targeted MRM approach identified similar numbers of lipids to a conventional untargeted approach, but had better representation of 11 lipid classes commonly identified by both approaches. Based on the separation methods employed, the conventional untargeted approach could better detect phosphatidylcholine and sphingomyelin lipid classes. The targeted MRM approach had lower inter-day variability than the untargeted approach when tested using a small group of plasma samples. These studies highlight the advantages in using targeted MRM approaches for human plasma lipidomics analysis.
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Project description:AimsThis study aimed to develop a smartphone mirroring-based telepresence exercise program that can be performed at home while allowing for real-time feedback by instructors.MethodsFor this randomized controlled trial, 29 obese older women aged 66-87 years with ≥ 30% body fat were recruited at a senior citizen center. The intervention group was provided with the smartphone mirroring-based telepresence exercise program, in which participants exercised in their homes for 20-40 min three times a week for 12 weeks. Participants in the control group performed the same exercise program at the senior citizen center. Body composition and functional abilities were measured before and after the program.ResultsWomen in the intervention group showed a decrease in their body fat percentage (P = 0.026) and an increase in grip strength (P = 0.008). In the control group, women demonstrated a decrease in their weight (P = 0.006) and body fat percentage (P = 0.001) and an increase in skeletal muscle (P = 0.044) and grip strength (P = 0.006).ConclusionSmartphone mirroring-based telepresence exercises at home lower body fat percentage and increase muscle strength similar to traditional group exercises. They present an innovative way for obese older women to improve and maintain their health.Trial registrationClinical Research Information Service KCT0006147.
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Project description:BackgroundLipidomic analysis was performed to explore differences in lipid profiles between plasma from lean and obese subjects, followed by in vitro methods to examine a role for the identified lipids in endothelial cell pathophysiology.MethodsPlasma was collected from 15 morbidly obese and 13 control subjects. Lipids were extracted from plasma and analyzed using LC/MS, and MS/MS to characterize lipid profiles and identify lipids that are elevated in obese subjects compared to lean.ResultsOrthogonal partial least squares-discriminant analysis (OPLS-DA) modelling showed that lipid profiles were significantly different in obese subjects compared to lean. Analysis of lipids that were driving group separation in the OPLS-DA model and that were significantly elevated in the obese group led to identification of a group of ether-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids of interest. Treatment of human coronary artery endothelial cells with the ether-linked phosphatidylethanolamine induced expression of cell adhesion molecules, a hallmark of endothelial cell activation. However, oxidized phosphatidylcholine products that can induce endothelial cell activation in vitro, were not significantly different between groups in vivo.ConclusionThese data suggest a role for ether-linked lipids in obesity associated dyslipidemia and vascular disease.
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Project description:BACKGROUND:Telomere length is inversely associated with the senescence and aging process. Parallelly, obesity can promote telomere shortening. Evidence suggests that physical activity may promote telomere elongation. OBJECTIVE:This study's objective is to evaluate the effects of combined exercise training on telomere length in obese women. DESIGN AND METHODS:Twenty pre-menopausal women (BMI 30-40 kg/m2, 20-40 years) submitted to combined training (strength and aerobic exercises), but only 13 finished the protocol. Each exercise session lasted 55 min/day, three times a week, throughout 8 weeks. Anthropometric data, body composition, physical performance (Vo2max), and 8-h fasting blood samples were taken before and after 8 weeks of training. Leukocyte DNA was extracted for telomere length by RT-qPCR reaction, using the 2-ΔΔCt methodology. RESULTS:After the training intervention, significant differences (p < 0.05) were observed in telomere length (respectively before and after, 1.03 ± 0.04 to 1.07 ± 0.04 T/S ratio), fat-free mass (46 ± 7 to 48 ± 5 kg), Vo2max (35 ± 3 to 38 ± 3 ml/kg/min), and waist circumference (96 ± 8 to 90 ± 6 cm). In addition, an inverse correlation between waist circumference and telomere length was found, before (r = - 0.536, p = 0.017) and after (r = - 0.655, p = 0.015) exercise training. CONCLUSION:Combined exercise promoted leukocyte telomere elongation in obese women. Besides, the data suggested that greater waist circumference may predict shorter telomere length. CLINICAL TRIAL REGISTRATION:ClinicalTrails.gov, NCT03119350. Retrospectively registered on 18 April 2017.
| S-EPMC6965549 | biostudies-literature
Project description:BackgroundWith fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide.MethodsComprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes.ResultsWith high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking.ConclusionsThe changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.
| S-EPMC10123985 | biostudies-literature
Project description:BackgroundLow physical activity (PA) during the postpartum period is associated with weight retention. While patterns of PA have been examined in normal weight women during this period, little is known about PA among overweight and obese women. The aim of this cross-sectional study was to investigate PA and determine the proportion of women meeting recommendations for PA.MethodsWomen (n = 491), with a body mass index (BMI) ≥ 25 kg/m² were enrolled in a behavioral intervention. PA was assessed at six weeks postpartum using the Seven-Day PA Recall.ResultsWomen averaged 923 ± 100 minutes/day of sedentary/ light and 33 ± 56 minutes/day of combined moderate, hard, and very hard daily activity. Women with a BMI ≥ 40 kg/m² reported more time in sedentary/light activities and less hours of sleep than those with a lower BMI. Only 34% met national PA guidelines; this proportion was significantly lower among blacks (OR 0.5, CI 0.3-0.9).ConclusionsThese overweight and obese postpartum women reported a large percentage of time spent in sedentary/light activity, and a high proportion failed to meet minimal guidelines for PA. Promotion of PA in the postpartum period should focus on reducing sedentary behaviors and increasing moderate PA.
| S-EPMC3613777 | biostudies-literature