BACKGROUND: Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events. AIM: We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque. METHODS: This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques. RESULTS: The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification. CONCLUSIONS: Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.
- MeSH
- aterosklerotický plát * krev MeSH
- biologické markery * krev MeSH
- chromatografie kapalinová MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidomika * MeSH
- lipidy * krev MeSH
- nemoci arterie carotis * krev diagnóza MeSH
- prediktivní hodnota testů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spontánní ruptura MeSH
- studie případů a kontrol MeSH
- tandemová hmotnostní spektrometrie * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Regular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well understood. Metabolomics may have a promising research potential to extend our knowledge and use it in the attempts to find a long-term and sustainable personalized approach in exercise and diet recommendations. OBJECTIVE: The main aim was to investigate the effect of the 12 week very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) on lipidomic and metabolomic profiles in individuals with overweight and obesity. METHODS: The participants (N = 91) were randomly allocated to HIIT (N = 22), VLCHF (N = 25), VLCHF + HIIT (N = 25) or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4, 8 and 12 weeks. The samples were then subjected to untargeted lipidomic and metabolomic analyses using reversed phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry. RESULTS: The VLCHF diet affected plasma lipids considerably while the effect of HIIT was unremarkable. Already after 4 weeks of intervention substantial changes of plasma lipids were found in both VLCHF diet groups. The changes persisted throughout the entire 12 weeks of the VLCHF diet. Specifically, acyl carnitines, plasmalogens, fatty acyl esters of hydroxy fatty acid, sphingomyelin, ceramides, cholesterol esters, fatty acids and 4-hydroxybutyric were identified as lipid families that increased in the VLCHF diet groups whereas lipid families of triglycerides and glycerophospholipids decreased. Additionally, metabolomic analysis showed a decrease of theobromine. CONCLUSIONS: This study deciphers the specific responses to a VLCHF diet, HIIT and their combination by analysing untargeted lipidomic and metabolomic profile. VLCHF diet caused divergent changes of plasma lipids and other metabolites when compared to the exercise and control group which may contribute to a better understanding of metabolic changes and the appraisal of VLCHF diet benefits and harms. CLINICAL TRIAL REGISTRY NUMBER: NCT03934476, registered 1st May 2019 https://clinicaltrials.gov/ct2/show/NCT03934476?term=NCT03934476&draw=2&rank=1 .
Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5'-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time - polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.
- Publikační typ
- časopisecké články MeSH
Gut microbes have been recognized to convert human bile acids by deconjugation, dehydroxylation, dehydrogenation, and epimerization of the cholesterol core, but the ability to re-conjugate them with amino acids as an additional conversion has been recently described. These new bile acids are known as microbially conjugated bile acids (MCBAs). The aim of this study was to evaluate the MCBAs diversity produced by the gut microbiota through a metabolomics approach. In this study, fresh fecal samples from healthy donors were evaluated to explore the re-conjugation of chenodeoxycholic and 3-oxo-chenodeoxycholic acids by the human gut microbiota. No significant differences were found between the conversion trend of both BAs incubations. The in vitro results showed a clear trend to first accumulate the epimer isoursochenodeoxycholic acid and the dehydroxylated lithocholic acid derivatives in samples incubated with chenodeoxycholic and 3-oxo-chenodeoxycholic acid. They also showed a strong trend for the production of microbially conjugated dehydroxylated bile acids instead of chenodeoxycholic backbone conjugates. Different molecules and isomers of MCBAs were identified, and the new ones, valolithocholate ester and leucolithocholate ester, were identified and confirmed by MS/MS. These results document the gut microbiota's capability to produce esters of MCBAs on hydroxyls of the sterol backbone in addition to amides at the C24 acyl site. This study opens a new perspective to study the BAs diversity produced by the human gut microbiota.
Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n-3 polyunsaturated fatty acids (n-3-PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n-3-PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double-blind placebo-controlled trial (3.6 g/day n-3-PUFA vs. placebo). During the 1-year follow-up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n-3-PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment-and weight reduction-was observed; furthermore, this effect was clearly potentiated by n-3-PUFA treatment (P < 0.005). In addition, n-3-PUFA treatment resulted in substantial changes in the plasma lipidome, with n-3-PUFA-enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n-3-PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.
Alterations in lipid metabolism mediated by oxidative stress play a key role in the process of atherosclerosis and superimposed thrombosis; these can lead to acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Multiple studies have shown that the formation of atheromatous lesions is initiated by oxidation of low-density lipoproteins incorporated into the intima of the vessel wall. Here, we studied lipids in plasma samples from three cohorts: 61 patients with ACS (group A), 49 patients with AIS (group D), and 82 controls (group K). Untargeted lipidomics based on high-performance liquid chromatography coupled to mass spectrometry (UHPLC-HRMS) was employed to obtain comprehensive information on whether relationships exist between these patient categories based on lipid patterns. In addition, malondialdehyde (MDA) as a standard marker of oxidative stress was monitored. The most characteristic lipids in group K were fatty acyls of hydroxyfatty acids (FAHFAs). As expected, MDA concentrations were the lowest in group K. Our findings can better explain ongoing pathologies, both acute and chronic, with the potential for future diagnosis and treatment.
- Publikační typ
- časopisecké články MeSH
Omega-3 polyunsaturated fatty acids (ω-3PUFAs) are introduced into parenteral nutrition (PN) as hepatoprotective but may be susceptible to the lipid peroxidation while olive oil (OO) is declared more peroxidation resistant. We aimed to estimate how the lipid composition of PN mixture affects plasma and erythrocyte lipidome and the propensity of oxidative stress. A cross-sectional comparative study was performed in a cohort of adult patients who were long-term parenterally administered ω-3 PUFAs without (FO/-, n = 9) or with (FO/OO, n = 13) olive oil and healthy age- and sex-matched controls, (n = 30). Lipoperoxidation assessed as plasma and erythrocyte malondialdehyde content was increased in both FO/- and FO/OO groups but protein oxidative stress (protein carbonyls in plasma) and low redox status (GSH/GSSG in erythrocytes) was detected only in the FO/- subcohort. The lipidome of all subjects receiving ω-3 PUFAs was enriched with lipid species containing ω-3 PUFAs (FO/-˃FO/OO). Common characteristic of all PN-dependent patients was high content of fatty acyl-esters of hydroxy-fatty acids (FAHFAs) in plasma while acylcarnitines and ceramides were enriched in erythrocytes. Plasma and erythrocyte concentrations of plasmanyls and plasmalogens (endogenous antioxidants) were decreased in both patient groups with a significantly more pronounced effect in FO/-. We confirmed the protective effect of OO in PN mixtures containing ω-3 PUFAs.
- MeSH
- antioxidancia metabolismus MeSH
- dospělí MeSH
- erytrocyty metabolismus MeSH
- kyseliny mastné omega-3 farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidomika MeSH
- lipidy krev MeSH
- nemoci střev krev terapie MeSH
- olivový olej farmakologie MeSH
- oxidační stres účinky léků MeSH
- parenterální výživa škodlivé účinky metody MeSH
- průřezové studie MeSH
- rybí oleje farmakologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tukové emulze intravenózní farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). Omega-3 polyunsaturated fatty acids (PUFA) were reported to alleviate PNALD but the underlying mechanisms have not been fully unraveled yet. Using omics´ approach, we determined serum and liver lipidome, liver proteome, and liver bile acid profile as well as markers of inflammation and oxidative stress in rats administered either ω-6 PUFA based lipid emulsion (Intralipid) or ω-6/ω-3 PUFA blend (Intralipid/Omegaven) via the enteral or parenteral route. In general, we found that enteral administration of both lipid emulsions has less impact on the liver than the parenteral route. Compared with parenterally administered Intralipid, PN administration of ω-3 PUFA was associated with 1. increased content of eicosapentaenoic (EPA)- and docosahexaenoic (DHA) acids-containing lipid species; 2. higher abundance of CYP4A isoenzymes capable of bioactive lipid synthesis and the increased content of their potential products (oxidized EPA and DHA); 3. downregulation of enzymes involved CYP450 drug metabolism what may represent an adaptive mechanism counteracting the potential negative effects (enhanced ROS production) of PUFA metabolism; 4. normalized anti-oxidative capacity and 5. physiological BAs spectrum. All these findings may contribute to the explanation of ω-3 PUFA protective effects in the context of PN.
- MeSH
- emulze MeSH
- enterální výživa metody MeSH
- fosfolipidy MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina eikosapentaenová chemie MeSH
- kyseliny dokosahexaenové chemie MeSH
- kyseliny mastné omega-3 chemie MeSH
- kyslík metabolismus MeSH
- lipidomika MeSH
- lipidy chemie MeSH
- malondialdehyd metabolismus MeSH
- metabolomika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- oxidační stres MeSH
- parenterální výživa metody MeSH
- potkani Wistar MeSH
- proteom metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rybí oleje MeSH
- sójový olej MeSH
- zánět MeSH
- žlučové kyseliny a soli analýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
