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The Journal of Nutrition Oct 2020In the settings of primary and secondary prevention for coronary artery disease (CAD), a crucial role is played by some key molecules involved in triglyceride (TG)...
The Positive Association between Plasma Myristic Acid and ApoCIII Concentrations in Cardiovascular Disease Patients Is Supported by the Effects of Myristic Acid in HepG2 Cells.
BACKGROUND
In the settings of primary and secondary prevention for coronary artery disease (CAD), a crucial role is played by some key molecules involved in triglyceride (TG) metabolism, such as ApoCIII. Fatty acid (FA) intake is well recognized as a main determinant of plasma lipids, including plasma TG concentration.
OBJECTIVES
The aim was to investigate the possible relations between the intakes of different FAs, estimated by their plasma concentrations, and circulating amounts of ApoCIII.
METHODS
Plasma samples were obtained from 1370 subjects with or without angiographically demonstrated CAD (mean ± SD age: 60.6 ± 11.0 y; males: 75.8%; BMI: 25.9 ± 4.6 kg/m2; CAD: 73.3%). Plasma lipid, ApoCIII, and FA concentrations were measured. Data were analyzed by regression models adjusted for FAs and other potential confounders, such as sex, age, BMI, diabetes, smoking, and lipid-lowering therapies. The in vitro effects of FAs were tested by incubating HepG2 hepatoma cells with increasing concentrations of selected FAs, and the mRNA and protein contents in the cells were quantified by real-time RT-PCR and LC-MS/MS analyses.
RESULTS
Among all the analyzed FAs, myristic acid (14:0) showed the most robust correlations with both TGs (R = 0.441, P = 2.6 × 10-66) and ApoCIII (R = 0.327, P = 1.1 × 10-31). By multiple regression analysis, myristic acid was the best predictor of both plasma TG and ApoCIII variability. Plasma TG and ApoCIII concentrations increased progressively at increasing concentrations of myristic acid, independently of CAD diagnosis and gender. Consistent with these data, in the in vitro experiments, an ∼2-fold increase in the expression levels of the ApoCIII mRNA and protein was observed after incubation with 250 μM myristic acid. A weaker effect (∼30% increase) was observed for palmitic acid, whereas incubation with oleic acid did not affect ApoCIII protein or gene expression.
CONCLUSIONS
Plasma myristic acid is associated with increased ApoCIII concentrations in cardiovascular patients. In vitro experiments indicated that myristic acid stimulates ApoCIII expression in HepG2 cells.
Topics: Aged; Apolipoprotein C-III; Cardiovascular Diseases; Gene Expression Regulation; Hep G2 Cells; Hepatocytes; Humans; Male; Middle Aged; Myristic Acid; RNA, Messenger
PubMed: 32710763
DOI: 10.1093/jn/nxaa202 -
Journal of Proteome Research Feb 2018Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed countries. At the moment, no effective screening system is available....
Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed countries. At the moment, no effective screening system is available. Here, we evaluate the diagnostic performance of a serum metabolomic signature. Two enrollments were carried out, one consisting of 168 subjects: 88 with EC and 80 healthy women, was used for building the classification models. The second (used to establish the performance of the classification algorithm) was consisted of 120 subjects: 30 with EC, 30 with ovarian cancer, 10 with benign endometrial disease, and 50 healthy controls. Two ensemble models were built, one with all EC versus controls (Model I) and one in which EC patients were aggregated according to their histotype (Model II). Serum metabolomic analysis was conducted via gas chromatography-mass spectrometry, while classification was done by an ensemble learning machine. Accuracy ranged from 62% to 99% for the Model I and from 67% to 100% for the Model II. Ensemble model showed an accuracy of 100% both for Model I and II. The most important metabolites in class separation were lactic acid, progesterone, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, and valine. The serum metabolomics signature of endometrial cancer patients is peculiar because it differs from that of healthy controls and from that of benign endometrial disease and from other gynecological cancers (such as ovarian cancer).
Topics: 3-Hydroxybutyric Acid; Aged; Biomarkers, Tumor; Case-Control Studies; Diagnosis, Differential; Endometrial Neoplasms; Endometriosis; Endometrium; Female; Gas Chromatography-Mass Spectrometry; Homocysteine; Humans; Lactic Acid; Linoleic Acid; Machine Learning; Metabolome; Metabolomics; Middle Aged; Myristic Acid; Progesterone; Prospective Studies; Stearic Acids; Threonine; Valine
PubMed: 29235868
DOI: 10.1021/acs.jproteome.7b00503 -
Current Drug Delivery 2022The bitter taste and strong irritation of valnemulin hydrochloride limit its wide clinical application in pigs by oral.
BACKGROUND
The bitter taste and strong irritation of valnemulin hydrochloride limit its wide clinical application in pigs by oral.
METHOD
In order to improve its palatability and residence time in the body, the valnemulin hydrochloride taste-masking granules with sustained-release were prepared by combining solid dispersion based on fatty acid with wet granulation. The formulation was screened by orthogonal test with content, yield, grain size and angle of repose as evaluation indexes.
RESULT
The results showed that the optimal granules were composed of corn starch, sucrose, citric acid, valnemulin hydrochloride and myristic acid at a ratio of 40: 20: 20: 11: 19. The daily feed intake of pigs in the optimum taste-masking granule groups was similar to that of its self-control, and significantly higher than that in the valnemulin hydrochloride active ingredient group, suggesting that the optimum granules have satisfactory palatability. The prepared granules improved the oral bioavailability of valnemulin hydrochloride by 3.04 folds and extended its mean residence time (MRT) by 2.33 folds.
CONCLUSION
The granules developed in this study could obviously improve the palatability and sustained release of valnemulin hydrochloride. The producing method of granules by combining solid dispersion powder with wet granulation can provide ideas for other drugs with poor palatability and a short half-life.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Biological Availability; Diterpenes; Drug Compounding; Powders; Solubility; Swine; Taste
PubMed: 34477518
DOI: 10.2174/1567201818666210903151658 -
Journal of the Science of Food and... Feb 2024Lipids and carbohydrates perform essential functions in foods. In recent decades, food scientists have studied the effects of carbohydrate-lipid interactions on the...
BACKGROUND
Lipids and carbohydrates perform essential functions in foods. In recent decades, food scientists have studied the effects of carbohydrate-lipid interactions on the functional properties of food. However, the ways in which carbohydrate-lipid complex-derived materials affect the biological system are unknown. In this study, a myristic acid-potato starch complex was created using a simple cooking approach. The complex was employed as a precursor for the fabrication of myristic acid-potato starch complex-based nanostructured materials (MPS-NMs) through a liquid-liquid extraction approach. A study was conducted on the structural and cytotoxic features of the fabricated MPS-NMs.
RESULTS
Transmission electron microscopy images confirmed the formation of spherical nanostructures, 3-60 nm in size. After 24 h exposure, the chloroform fraction-based and n-hexane fraction-based MPS-NMs increased cell death by ~90% and ~ 82%, respectively. Chloroform fraction-based MPS-NMs (CMPS-NMs) triggers apoptotic cell death in human mesenchymal stem cells (hMSCs). n-Hexane fraction-based MPS-NMs (HMPS-NMs) treated cells have red color-intact nuclei, attributed to necrotic cell death. The CMPS-NMs and HMPS-NMs significantly decreased the mitochondria membrane potential and increased the intracellular reactive oxygen species (ROS) levels. We observed significant downregulation in flavin-containing monooxygenase (FMO), Ataxia Telangiectasia Mutated (ATM), and uridine diphosphate glucuronosyltransferases (UGT) gene expression levels in the exposed cells of CMPS-NMs and HMPS- NMs. In addition, we found upregulation of glutathione-disulfide reductase (GSR) and glutathione S-transferase A4 (GSTA4) genes in CMPS-NMs, and HMPS-NMs exposure.
CONCLUSION
The cooking process may lead to the formation of nanostructured material in food systems. Chloroform fraction-based MPS-NMs and HMPS-NMs may contribute to cell metabolic disorders. © 2023 Society of Chemical Industry.
Topics: Humans; Myristic Acid; Solanum tuberosum; Chloroform; Nanostructures; Starch; Carbohydrates
PubMed: 37872732
DOI: 10.1002/jsfa.13071 -
Cellular & Molecular Immunology Apr 2021Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases (NMTs), which are ubiquitous enzymes in eukaryotes. Specifically,... (Review)
Review
Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases (NMTs), which are ubiquitous enzymes in eukaryotes. Specifically, attachment of a myristoyl group is vital for proteins participating in various biological functions, including signal transduction, cellular localization, and oncogenesis. Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections. In this review, we describe the current understanding of protein N-myristoylation (mainly focusing on myristoyl switches) and summarize its crucial roles in regulating innate immune responses, including TLR4-dependent inflammatory responses and demyristoylation-induced innate immunosuppression during Shigella flexneri infection. Furthermore, we examine the role of myristoylation in viral assembly, intracellular host interactions, and viral spread during human immunodeficiency virus-1 (HIV-1) infection. Deeper insight into the relationship between protein N-myristoylation and innate immunity might enable us to clarify the pathogenesis of certain infectious diseases and better harness protein N-myristoylation for new therapeutics.
Topics: Dysentery, Bacillary; HIV; HIV Infections; Humans; Immunity, Innate; Myristic Acid; Protein Processing, Post-Translational; Proteins; Shigella flexneri
PubMed: 33731917
DOI: 10.1038/s41423-021-00663-2 -
The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.The EMBO Journal Feb 2024The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal...
The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits that mirror human spastic paraplegia. Via pulldown-mass spectrometry analyses, we find that DDHD2 binds to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1 mouse model of human early infantile encephalopathy associated with intellectual disability and motor dysfunction, we show that STXBP1 controls targeting of DDHD2 to the plasma membrane and generation of saturated FFAs in the brain. These findings suggest key roles for DDHD2 and STXBP1 in lipid metabolism and in the processes of synaptic plasticity, learning, and memory.
Topics: Animals; Mice; Brain; Fatty Acids, Nonesterified; Memory; Memory, Long-Term; Munc18 Proteins; Phospholipases
PubMed: 38316990
DOI: 10.1038/s44318-024-00030-7 -
International Journal of Molecular... Mar 2022Non-alcoholic fatty liver disease is a pathology with a hard-to-detect onset and is estimated to be present in a quarter of the adult human population. To improve our...
Non-alcoholic fatty liver disease is a pathology with a hard-to-detect onset and is estimated to be present in a quarter of the adult human population. To improve our understanding of the development of non-alcoholic fatty liver disease, we treated a human hepatoma cell line model, HepG2, with increasing concentrations of common fatty acids, namely myristic, palmitic and oleic acid. To reproduce more physiologically representative conditions, we also included combinations of these fatty acids and monitored the cellular response with an in-depth proteomics approach and imaging techniques. The two saturated fatty acids initially presented a similar phenotype of a dose-dependent decrease in growth rates and impaired lipid droplet formation. Detailed analysis revealed that the drop in the growth rates was due to delayed cell-cycle progression following myristic acid treatment, whereas palmitic acid led to cellular apoptosis. In contrast, oleic acid, as well as saturated fatty acid mixtures with oleic acid, led to a dose-dependent increase in lipid droplet volume without adverse impacts on cell growth. Comparing the effects of harmful single-fatty-acid treatments and the well-tolerated fatty acid mixes on the cellular proteome, we were able to differentiate between fatty-acid-specific cellular responses and likely common lipotoxic denominators.
Topics: Fatty Acids; Fatty Acids, Nonesterified; Hepatocytes; Humans; Non-alcoholic Fatty Liver Disease; Oleic Acid; Palmitic Acid; Proteome
PubMed: 35328776
DOI: 10.3390/ijms23063356 -
Journal of Experimental Zoology. Part... Aug 2021The Chilo partellus (Crambidae: Lepidoptera) larvae undergoes both hibernation and estivation in India. Although, much has been done on reproductive physiological...
The Chilo partellus (Crambidae: Lepidoptera) larvae undergoes both hibernation and estivation in India. Although, much has been done on reproductive physiological aspects, little is known about biochemical changes happening during hibernation and estivation in C. partellus. Thus, we mapped changes in amino acid and lipophilic profiles of C. partellus larvae while undergoing hibernation and estivation using high-performance liquid chromatography and gas chromatography mass spectroscopy. The studies revealed higher amounts of amino acids namely, serine, glycine, histidine, arginine, proline, tyrosine, and methionine in estivation, while lower in hibernation as compared with nondiapause larvae of C. partellus. Furthermore, the amounts of aspartic acid, glutamic acid, and alanine in hibernation, and threonine, valine, isoleucine, phenylalanine, and leucine in estivation were on par with nondiapause larvae. The lipophilic compounds namely, linoleic acid, stearic acid, eicosanoic acid, and n-pentadecanol were lower in hibernation than estivation and nondiapause larvae of C. partellus. Palmitoleic acid and methyl 3-methoxytetradecanoate contents were higher in hibernation than estivation and nondiapause, while myristic acid and lathosterol contents were higher in estivation than hibernation and nondiapause larvae of C. partellus. Cholesterol content was higher, while squalene and gamma-ergostenol were lower in hibernation and estivation as compared with nondiapause larvae of C. partellus. These findings suggest that certain amino acids may be constituents of heat-shock proteins and help C. partellus during estivation. However, the lipophilic compounds could be helpful in maintaining development during hibernation and estivation in C. partellus.
Topics: Amino Acids; Animals; Diapause; Estivation; Larva; Moths
PubMed: 34185965
DOI: 10.1002/jez.2502 -
Molecular Plant-microbe Interactions :... Jun 2022Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de...
Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de novo synthase (FAS), they depend on host-derived fatty acids. AMF colonization is accompanied by expression of specific lipid genes and synthesis of -2 monoacylglycerols (MAGs). It is unknown how host-derived fatty acids are taken up by AMF. We describe the characterization of two AMP-binding domain protein genes from , and , with sequence similarity to (). Uptake of C-myristic acid (14:0) and, to a lesser extent, C-palmitic acid (16:0) was enhanced after expression of or in Δ cells. The uptake of H-labeled fatty acids from H-myristoylglycerol or H-palmitoylglycerol was also increased after and expression in Δ, but intact H-MAGs were not detected. and expression was induced in colonized roots compared with extraradical mycelium. C-label in the AMF-specific palmitvaccenic acid (16:1Δ11) and eicosatrienoic acid (20:3) were detected in colonized roots only when C-acetate was supplemented but not C-fatty acids, demonstrating that de novo synthesized, host-derived fatty acids are rapidly taken up by from the roots. The results show that RiFAT1 and RiFAT2 are involved in the uptake of myristic acid (14:0) and palmitic acid (16:0), while fatty acids from MAGs are only taken up after hydrolysis. Therefore, the two proteins might be involved in fatty acid import into the fungal arbuscules in colonized roots.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Adenosine Monophosphate; Carrier Proteins; Fatty Acid Transport Proteins; Fatty Acids; Fungi; Glomeromycota; Mycorrhizae; Myristic Acids; Palmitic Acids; Plant Roots; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35285673
DOI: 10.1094/MPMI-01-22-0026-R -
Progress in Lipid Research Jan 2022Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine... (Review)
Review
Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine residues through amide bonds or lysine and cysteine side chains directly or indirectly via glycerol thioester and ester linkages. Before transfer to proteins, myristate must be activated into myristoyl coenzyme A in eukaryotes or, in bacteria, to derivatives like phosphatidylethanolamine. Myristate originates through de novo biosynthesis (e.g., plants), from external uptake (e.g., human tissues), or from mixed origins (e.g., unicellular organisms). Myristate usually serves as a molecular anchor, allowing tagged proteins to be targeted to membranes and travel across endomembrane networks in eukaryotes. In this review, we describe and discuss the metabolic origins of protein-bound myristate. We review strategies for in vivo protein labeling that take advantage of click-chemistry with reactive analogs, and we discuss new approaches to the proteome-wide discovery of myristate-containing proteins. The machineries of myristoylation are described, along with how protein targets can be generated directly from translating precursors or from processed proteins. Few myristoylation catalysts are currently described, with only N-myristoyltransferase described to date in eukaryotes. Finally, we describe how viruses and bacteria hijack and exploit myristoylation for their pathogenicity.
Topics: Acyltransferases; Fatty Acids; Humans; Myristic Acid; Protein Processing, Post-Translational; Proteins
PubMed: 34793862
DOI: 10.1016/j.plipres.2021.101139