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Molecules (Basel, Switzerland) Jan 2024Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis, synaptic plasticity, and cognition. BDNF is a neurotrophin that binds to tropomyosin...
Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis, synaptic plasticity, and cognition. BDNF is a neurotrophin that binds to tropomyosin receptor kinase B (TrkB), a specific receptor on target cell surfaces; it acts on neuronal formation, development, growth, and repair via transcription factors, such as cAMP response element-binding protein (CREB), and it is involved in learning and memory. BDNF expression is decreased in patients with Alzheimer's disease (AD). Exercise and the intake of several different foods or ingredients can increase BDNF expression, as confirmed with lutein, xanthophylls (polar carotenoids), and ethanolamine plasmalogen (PlsEtn), which are present at high levels in the brain. This study examined the effects of combining lutein and PlsEtn using lutein-rich Chlorella and ascidian extracts containing high levels of PlsEtn bearing docosahexaenoic acid, which is abundant in the human brain, on the activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus of Sprague-Dawley rats. Although activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus was not observed in Chlorella or ascidian PlsEtn monotherapy, activation was observed with combination therapy at an equal dose. The results of this study suggest that the combination of Chlorella and ascidian PlsEtn may have a preventive effect against dementia, including AD.
Topics: Humans; Rats; Animals; Chlorella; Brain-Derived Neurotrophic Factor; Lutein; Rats, Sprague-Dawley; Signal Transduction; Brain; Alzheimer Disease; Plasmalogens
PubMed: 38257270
DOI: 10.3390/molecules29020357 -
Cardiovascular Diabetology Jan 2024Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma...
BACKGROUND
Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD.
METHODS
The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models.
RESULTS
Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period.
CONCLUSIONS
This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease.
TRIAL REGISTRATION
ISRCTN35739639.
Topics: Humans; Female; Aged; Male; Diabetes Mellitus, Type 2; Fabaceae; Cardiovascular Diseases; Cross-Sectional Studies; Diet, Mediterranean; Risk Factors
PubMed: 38245716
DOI: 10.1186/s12933-023-02111-z -
Biological & Pharmaceutical Bulletin 2024Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular...
Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular homeostasis including neural transmission. Therefore, reductions of plasmalogens have been associated with neurodegenerative disorders, such as Alzheimer's disease (AD). To evaluate the potential protective effects of plasmalogens against the pathology of AD, protein expression levels of key factors in amyloid precursor protein (APP) metabolic processes were examined using human neuroblastoma SH-SY5Y cells. Here, phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) was shown to reduce protein expression levels of β-site APP cleaving enzyme 1 (BACE1), clusterin, and Tau, factors involved in the amyloid β-associated pathogenesis of AD. Thus, PC-PLS-18 may have preventive effects against AD by delaying the onset risk for a certain period.
Topics: Humans; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Plasmalogens; Aspartic Acid Endopeptidases; Oleic Acid; Phosphatidylcholines; Neuroblastoma; Alzheimer Disease; Amyloid beta-Protein Precursor
PubMed: 38233149
DOI: 10.1248/bpb.b23-00787 -
Metabolomics : Official Journal of the... Dec 2023Regular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well... (Randomized Controlled Trial)
Randomized Controlled Trial
A lipidomic and metabolomic signature of a very low-carbohydrate high-fat diet and high-intensity interval training: an additional analysis of a randomized controlled clinical trial.
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 .
Topics: Humans; Lipidomics; Diet, High-Fat; High-Intensity Interval Training; Metabolomics; Triglycerides; Carbohydrates
PubMed: 38141101
DOI: 10.1007/s11306-023-02071-1 -
Redox Biochemistry and Chemistry Dec 2023Myeloperoxidase and eosinophil peroxidase exert their antimicrobial functions through the oxidative actions of their hypohalous acid products. Plasmalogen phospholipids...
Myeloperoxidase and eosinophil peroxidase exert their antimicrobial functions through the oxidative actions of their hypohalous acid products. Plasmalogen phospholipids are particularly susceptible to oxidation of their vinyl ether functional group by hypohalous acids. This produces a family of halogenated lipid products with pro-inflammatory roles and potential biomarker utility. The initial product of plasmalogen oxidation by HOCl is 2-chlorofatty aldehyde, which has been shown to play a key role at the blood-endothelium interface. and studies indicate increased endothelial barrier permeability, neutrophil chemotaxis, neutrophil and platelet adherence to endothelium, and promotion of erythrocyte lysis as some of its effects. These effects may be due to protein modification by 2-chlorofatty aldehyde. 2-Chlorofatty aldehyde is metabolized by host dehydrogenases to 2-chlorofatty acid. While it is less chemically reactive, 2-chlorofatty acid has partial overlap of pro-inflammatory effects with 2-chlorofatty aldehyde and unique actions such as induction of neutrophil extracellular trap formation. The stability of 2-chlorofatty acid in plasma also makes it well-suited as a biomarker of HOCl generation, and its plasma levels may be predictive of disease outcomes. 2-Bromofatty aldehydes and acids are produced analogously from HOBr reaction with plasmalogens. Their functions have yet to be well-elucidated, though similarities with chlorolipids have been observed, and increased reactivity with proteins is expected through enhanced electrophilicity of the alpha carbon. Altogether, these halogenated lipids represent underexplored mediators of diseases involving excess hypohalous acid production.
PubMed: 38073668
DOI: 10.1016/j.rbc.2023.100011 -
Arthritis Research & Therapy Dec 2023Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment...
BACKGROUND
Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment (ULT). Our study aimed to evaluate differences in plasma lipidome between patients with asymptomatic HUA detected ≤ 40 years (HUA ≤ 40) and > 40 years, gout patients with disease onset ≤ 40 years (Gout ≤ 40) and > 40 years, and normouricemic healthy controls (HC).
METHODS
Plasma samples were collected from 94 asymptomatic HUA (77% HUA ≤ 40) subjects, 196 gout patients (59% Gout ≤ 40), and 53 HC. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied.
RESULTS
Both HUA and gout patients showed alterations in lipid profiles with the most significant upregulation of phosphatidylethanolamines and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls. More profound changes were observed in HUA ≤ 40 and Gout ≤ 40 without ULT. Multivariate statistics differentiated HUA ≤ 40 and Gout ≤ 40 groups from HC with an overall accuracy of > 95%.
CONCLUSION
Alterations in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism. The most significant glycerophospholipid dysregulation was found in HUA ≤ 40 and Gout ≤ 40 patients, together with a correction of this imbalance with ULT.
Topics: Humans; Hyperuricemia; Uric Acid; Lipidomics; Gout; Gout Suppressants
PubMed: 38042879
DOI: 10.1186/s13075-023-03204-6 -
Respiratory Research Dec 2023It is now understood that ferroptosis plays a significant role in the progression of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract...
BACKGROUND
It is now understood that ferroptosis plays a significant role in the progression of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE). However, the mechanisms underlying this relationship remain largely unclear.
METHODS
In this study, we established a COPD mouse model through exposure to cigarette smoke particulates, followed by H&E staining, analysis of bronchoalveolar lavage fluid, and immunohistochemistry assay. A549 cells were exposed to increasing concentrations of CSE, with the addition of the ferroptosis activator erastin or the inhibitor Fer-1. Cell viability, LDH (lactate dehydrogenase) release, inflammatory cytokines, total ROS (reactive oxygen species), and lipid ROS were measured using the corresponding assay kits. The acetylation level of GNPAT was determined through immunoprecipitation. We assessed the expression levels of molecules involved in plasmalogen biosynthesis (FAR1, AGPS, and GNPAT), GPX4, and SIRT4 using quantitative real-time PCR, western blot analysis, and immunofluorescence staining.
RESULTS
CSE-induced lung tissue damage was initially observed, accompanied by oxidative stress, ferroptosis, and increased plasmalogen biosynthesis molecules (FAR1, AGPS, and GNPAT). CSE also induced ferroptosis in A549 cells, resulting in reduced cell viability, GSH, and GPX4 levels, along with increased LDH, ROS, MDA (malondialdehyde) levels, oxidized lipids, and elevated FAR1, AGPS, and GNPAT expression. Knockdown of GNPAT mitigated CSE-induced ferroptosis. Furthermore, we found that CSE regulated the acetylation and protein levels of GNPAT by modulating SIRT4 expression. Importantly, the overexpression of GNPAT countered the inhibitory effects of SIRT4 on ferroptosis.
CONCLUSIONS
Our study revealed GNPAT could be deacetylated by SIRT4, providing novel insights into the mechanisms underlying the relationship between CSE-induced ferroptosis and COPD.
Topics: Mice; Animals; Ferroptosis; Reactive Oxygen Species; Plasmalogens; Pulmonary Disease, Chronic Obstructive; Lung; Nicotiana
PubMed: 38041059
DOI: 10.1186/s12931-023-02613-0 -
International Journal of Biochemistry... 2023Phospholipids are highly diverse molecules with pleiotropic biological roles, from membrane components and signaling molecules, whose composition can change in response...
BACKGROUND
Phospholipids are highly diverse molecules with pleiotropic biological roles, from membrane components and signaling molecules, whose composition can change in response to both endogenous and external stimuli. Recent lipidomic studies on edible bivalve mollusks were focused on lipid nutritional value and growth requirements. However, no data are available on phospholipid profiles during bivalve larval development. In the model marine bivalve , early larvae (up to 48 hours post fertilization-hpf) undergo dramatic molecular and functional changes, including shell biogenesis and neurogenesis, that are sustained by egg lipid reserves. Changes in phospholipid composition may also occur participating in the complex processes of early development.
OBJECTIVE
The lipidome of eggs and early larval stages (24 and 48 hpf) was investigated in order to identify possible changes in phospholipid classes and related metabolic pathways that may play a role in key steps of development.
MATERIALS AND METHODS
Lipidomic analysis were performed by NMR spectroscopy and liquid chromatography-mass spectrometry (LC-MS), with focus on phospholipids. Shifts in relative species composition of phosphatidylcholine, phosphatidylethanolamine, plasmalogen, and ceramide aminoethylphosphonate-CAEP, the bivalve analogue of the main mammalian ceramide sphingomyelin, were observed. Expression of genes involved in ceramide homeostasis was also modulated from eggs to early larval stages.
RESULTS
The results represent the first data on changes in phospholipid composition in bivalve larvae and suggest a functional role of phospholipids in mussel early development.
CONCLUSION
The results underline the importance of lipidomic studies in bivalve larvae, in both physiological conditions and in response to environmental stress.
PubMed: 38020445
DOI: No ID Found -
Communications Chemistry Nov 2023Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation...
Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson's disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration.
PubMed: 37932487
DOI: 10.1038/s42004-023-01043-9 -
Frontiers in Microbiology 2023Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as , somewhat implying that...
Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as , somewhat implying that they evolved from a non-thermophilic background and that thermophiles, i.e., organisms with growth temperature optima (T) above 45°C, evolved from mesophilic organisms (T 25-45°C). On the contrary, it has also been argued that LUCA, the last universal common ancestor of and , may have been a thermophile, and mesophily is the derived trait. In this study, we took an experimental approach toward the evolution of a mesophile from a thermophile. We selected the acetogenic bacterium (T 66°C) since acetogenesis is considered ancient physiology and cultivated it at suboptimal low temperatures. We found that the lowest possible growth temperature (T) under the chosen conditions was 39°C. The bacterium was subsequently subjected to adaptive laboratory evolution (ALE) by serial transfer at 45°C. Interestingly, after 67 transfers (approximately 180 generations), the adapted strain Adpt45_67 did not grow better at 45°C, but a shift in the T to 60°C was observed. Growth at 45°C was accompanied by a change in the morphology as shorter, thicker cells were observed that partially occurred in chains. While the proportion of short-chain fatty acids increased at 50°C vs. 66°C in both strains, Adpt45_67 also showed a significantly increased proportion of plasmalogens. The genome analysis revealed 67 SNPs compared to the type strain, among these mutations in transcriptional regulators and in the cAMP binding protein. Ultimately, the molecular basis of the adaptation of to a lower T remains to be elucidated. The observed change in phenotype is the first experimental step toward the evolution of thermophiles growing at colder temperatures and toward a better understanding of the cold adaptation of thermophiles on early Earth.
PubMed: 37901835
DOI: 10.3389/fmicb.2023.1265216