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Adipocyte Dec 2022Metabolic disorders related to obesity are largely dependent on adipose tissue hypertrophy, which involves adipocyte hypertrophy and increased adipogenesis. Adiposize is...
Metabolic disorders related to obesity are largely dependent on adipose tissue hypertrophy, which involves adipocyte hypertrophy and increased adipogenesis. Adiposize is regulated by lipid accumulation as a result of increased lipogenesis (mainly lipid uptake in mature adipocytes) and reduced lipolysis. Using realtime 2D cell culture analyses of lipid uptake, we show (1) that high glucose concentration (4.5 g/L) was required to accumulate oleic acid increasing lipid droplet size until unilocularization similar to mature adipocytes in few days, (2) oleic acid reduced ( gene transcription and (3) insulin counteracted oleic acid-induced increase of lipid droplet size. Although the lipolytic activity observed in high low glucose (1 g/L) conditions was not altered, insulin was found to inhibit oleic acid induced gene transcription required for lipid storage such as Cell Death Inducing DFFA Like Effectors (CIDEC) and G0 switch gene S2), possibly through PPARA activity. Although this signalling pathway requires more detailed investigation, the results point out the differential mechanisms involved in the pro-adipogenic effect of insulin in absence its protective effect on adiposity in presence of oleic acid uptake.: AICAR, 5-Aminoimidazole-4-carboxamide-1-D-ribofuranoside; AMPK, AMP-Activated protein kinase, ASCs, adipose stem cell; ATGL, adipose triglyceride lipase; BSA, Bovine serum albumin; CEBPA, CCAAT enhancer binding protein alpha; CIDEs, Cell Death Inducing DFFA Like Effectors; dA, differentiated adipocyte; DMEM, Dulbecco's Modified Eagle's Medium; FABPs, Fatty Acid Binding Proteins; FAT/CD36, Fatty acid translocase; FCS, Foetal calf serum; FN1, fibronectin 1; FFA, free fatty acid; G0S2, G0 switch gene S2; GLUTs, Glucose transporters; GPR120, G protein-coupled receptor 120; HG, high glucose; HSL, hormone sensitive lipase; INSR, insulin receptor; LG, low glucose; OA, oleic acid; PBS, Phosphate buffer saline; PPARs, Peroxisome-Proliferator Activated Receptors; PKA, Protein kinase cyclic AMP-dependent; PKG, Protein kinase cyclic GMP dependent; PTGS2, cytochrome oxidase 2; RTCA, realtime cell analysis; TG, triglyceride.
Topics: Adipocytes; Fatty Acids; Glucose; Humans; Hypertrophy; Insulin; Lipolysis; Obesity; Oleic Acid; Protein Kinases
PubMed: 35946137
DOI: 10.1080/21623945.2022.2107784 -
Lipids in Health and Disease Jun 2020Inhalation of common air pollutants such as diesel and biodiesel combustion products can induce vascular changes in humans which may contribute to increased mortality...
BACKGROUND
Inhalation of common air pollutants such as diesel and biodiesel combustion products can induce vascular changes in humans which may contribute to increased mortality and morbidity associated with fine particulate matter exposures. Diesel, biodiesel, and other combustion byproducts contain fatty acid components capable of entering the body through particulate matter inhalation. Fatty acids can also be endogenously released into circulation following a systemic stress response to some inhaled pollutants such as ozone. When in the circulation, bioactive fatty acids may interact with cells lining the blood vessels, potentially inducing endothelial dysfunction. To examine whether fatty acids could potentially be involved in human vascular responses to air pollutants, we determined the effects of fatty acids and derivatives on important vascular cell functions.
METHODS
Human umbilical vein endothelial cells (HUVEC) were exposed in vitro to oleic acid (OA) or OA metabolites for 4-48 h. Cytotoxicity, vasodilator production (by ELISA measurement), mitochondrial function (using Sea Horse assays), and iron metabolism (inferred by ICP-OES measurements) were examined, with standard statistical testing (ANOVA, t-tests) employed.
RESULTS
Dose-dependent cytotoxicity was noted at 24 h, with 12-hydroxy OA more potent than OA. Mitochondrial stress testing showed that 12-hydroxy OA and OA induce mitochondrial dysfunction. Analysis of soluble mediator release from HUVEC showed a dose-dependent increase in prostaglandin F, a lipid involved in control of vascular tone, at 24 h (85% above controls) after OA-BSA exposure. RT-PCR analysis revealed OA did not induce changes in gene expression at noncytotoxic concentrations in exposed HUVEC, but 12-OH OA did alter ICAM and COX2 gene expression.
CONCLUSIONS
Together, these data demonstrate that FA may be capable of inducing cytotoxic effects and altering expression of mediators of vascular function following inhalation exposure, and may be implicated in air pollutant-induced deaths and hospitalizations. (267 of max 350 words).
Topics: Air Pollutants; Cyclooxygenase 2; Dinoprost; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Iron; Mitochondria; Oleic Acid; Ricinoleic Acids; Vasomotor System
PubMed: 32505182
DOI: 10.1186/s12944-020-01296-6 -
Molecules (Basel, Switzerland) Dec 2023Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for...
Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (, , , ) were designed and synthesized. The target product (compound ) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.
Topics: Humans; Lipid Metabolism; PPAR alpha; Carnitine O-Palmitoyltransferase; Non-alcoholic Fatty Liver Disease; Antipsychotic Agents; Ethylamines; Oleic Acid; Lipase; Indoles
PubMed: 38202597
DOI: 10.3390/molecules29010012 -
Respiratory Research Jan 2023Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of...
BACKGROUND
Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-β1 (TGF-β1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling.
METHODS
Female C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors.
RESULTS
The expression of SCD1 was increased in fibroblasts exposed to TGF-β1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-β1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation.
CONCLUSIONS
The data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.
Topics: Animals; Mice; Female; Proto-Oncogene Proteins c-akt; Transforming Growth Factor beta1; Phosphatidylinositol 3-Kinases; Oleic Acid; Sterol Regulatory Element Binding Protein 1; Airway Remodeling; Mice, Inbred C57BL; Signal Transduction; TOR Serine-Threonine Kinases; Lung; Asthma; Fibroblasts; Sirolimus; Stearoyl-CoA Desaturase
PubMed: 36627645
DOI: 10.1186/s12931-023-02313-9 -
Scientific Reports Apr 2021Essential oils are natural products that have great antimicrobial potential value against many fungi and bacteria. Rosa damascena Mill. is one of the most important...
Essential oils are natural products that have great antimicrobial potential value against many fungi and bacteria. Rosa damascena Mill. is one of the most important aromatic species of the Rosaceae family from which essential oil and economically valuable products can be obtained. The present study was designed to investigate the major compositions of the essential oil of this plant in Isfahan region of Iran and to identify its antibacterial and antifungal effects against 11 microorganisms causing human diseases and food spoilage. The essential oil was extracted by using the Clevenger apparatus and was analyzed by gas chromatography-mass spectrometry (GC-MS) technique. Its antimicrobial activity was evaluated by well diffusion, minimum inhibitory concentration (MIC) and minimum bactericide concentration (MBC). The results showed that the most important compounds of the essential oil were nonadecane (24.72%), heneicosane (19.325%), oleic acid (17.63%), and citronellol (12.61%). The results also showed that the highest inhibition zone of rose essential oil was against Aspergillus brasiliensis (15.00 ± 0.00 mm) and had a significant effect on Klebsiella pneumoniae (~ 8.00 mm). Also the rose oil had a significant inhibition and lethal effect against Candida albicans (MIC and MBC ~ 125 μg/mL), which is equivalent to the nystatin antibiotic (~ 125 μg/mL). Therefore, the essential oil of Damask rose can be considered as an alternative natural product for the prevention and treatment of fungal diseases in humans and against food spoilage as well.
Topics: Anti-Bacterial Agents; Aspergillus; Microbial Sensitivity Tests; Oils, Volatile; Oleic Acid
PubMed: 33850230
DOI: 10.1038/s41598-021-87604-1 -
Biological Research May 2024We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the...
BACKGROUND
We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.
RESULTS
We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts.
CONCLUSIONS
For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.
Topics: Oleic Acid; Myotonic Dystrophy; Humans; Cell Differentiation; MicroRNAs; Autophagy; Cell Line; RNA-Binding Proteins
PubMed: 38760841
DOI: 10.1186/s40659-024-00496-z -
BMC Veterinary Research Jun 2022Accumulation of lipid droplets (LDs) was recently observed in pyometra-affected uteri. As data about their nature and function are missing we intended to compare the...
BACKGROUND
Accumulation of lipid droplets (LDs) was recently observed in pyometra-affected uteri. As data about their nature and function are missing we intended to compare the localization, quality and quantity of LDs in canine healthy and pyometra-affected tissues and in an in vitro model.
METHODS AND RESULTS
We characterized LDs in healthy and pyometra uterine tissue samples as well as in canine endometrial epithelial cells (CEECs) in vitro by means of histochemistry, immunohistochemistry, transmission electron microscopy, western blot, and RT-qPCR. Oil Red O (ORO) staining and quantification as well as p-phenylenediamine staining showed a higher number of LDs in epithelial cells of pyometra samples. Immunohistochemistry revealed that the amount of LDs coated by perilipin2 (PLIN2) protein was also higher in pyometra samples. Transmission electron microscopy showed an increase of LD size in surface and glandular epithelial cells of pyometra samples. In cell culture experiments with CEECs, supplementation with oleic acid alone or in combination with cholesterol lead to an increased LD accumulation. The expression of PLIN2 at protein and mRNA level was also higher upon oleic acid supplementation. Most LDs were double positive for ORO and PLIN2. However, ORO positive LDs lacking PLIN2 coating or LDs positive for PLIN2 but containing a lipid class not detectable by ORO staining were identified.
CONCLUSIONS
We found differences in the healthy and pyometra-affected endometrium with respect to LDs size. Moreover, several kinds of LDs seem to be present in the canine endometrium. In vitro studies with CEECs could show their responsiveness to external lipids. Since epithelial cells reacted only to oleic acid stimulation, we assume that the cyclic lipid accumulation in the canine endometrium is based mainly on triglycerides and might serve as energy provision for the developing early embryo. Further studies are necessary to verify the complex role of lipids in the healthy and pyometra-affected canine endometrium.
Topics: Animals; Dog Diseases; Dogs; Endometrium; Female; Lipid Droplets; Oleic Acid; Pyometra; Uterus
PubMed: 35689217
DOI: 10.1186/s12917-022-03321-5 -
Scientific Reports May 2022Herein, esterification of oleic acid (OA) over tosylic acid functionalized eucalyptus bark biochar (TsOH-MBC) to synthesize fatty acid methyl ester (FAME) was...
Herein, esterification of oleic acid (OA) over tosylic acid functionalized eucalyptus bark biochar (TsOH-MBC) to synthesize fatty acid methyl ester (FAME) was investigated. The TsOH-MBC catalyst was prepared via pyrolysis-activation-sulfonation process at various impregnation ratios and was characterized by SEM, FTIR, EDX, XRD, BET, TGA and acid site density techniques. The catalytic performance of the sulfonated biochar catalyst was described in terms of acidity and FAME yield. 6 g of sulfonic acid loaded on 10 g of MBC (6TsOH-MBC) appeared to be most appropriate combination to achieve a highly active catalyst for the esterification of OA with 96.28% conversion to FAME at 80 °C for 5 h with catalyst loading of 4.0 wt% and 8:1 methanol/OA molar ratio. The catalytic reaction kinetic data were very well described by the second-order model, with a rate coefficient of 0.223 mL mol h at 80 °C and activation energy of 81.77 kJ mol. The thermodynamic parameters such as [Formula: see text], [Formula: see text] and [Formula: see text] were determined to be 78.94 kJ mol, 135.3 J mol K and 33.03 kJ mol, respectively. This research provided an environmentally friendly procedure for FAME production that could be replicated on a commercial scale.
Topics: Acids; Biofuels; Catalysis; Charcoal; Esterification; Eucalyptus; Oleic Acid; Plant Bark; Thermodynamics
PubMed: 35606402
DOI: 10.1038/s41598-022-12539-0 -
Cell Research Mar 2024Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by...
Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream G signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating G/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a "born to be activated and cold to enhance" model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis.
Topics: Animals; Mice; Adipose Tissue, Brown; Cell Membrane; Cryoelectron Microscopy; Ligands; Mice, Knockout; Oleic Acid; Receptors, G-Protein-Coupled
PubMed: 38287117
DOI: 10.1038/s41422-024-00932-5 -
Nitro-oleic acid regulates T cell activation through post-translational modification of calcineurin.Proceedings of the National Academy of... Jan 2023Nitro-fatty acids (NO-FAs) are unsaturated fatty acid nitration products that exhibit anti-inflammatory actions in experimental mouse models of autoimmune and allergic...
Nitro-fatty acids (NO-FAs) are unsaturated fatty acid nitration products that exhibit anti-inflammatory actions in experimental mouse models of autoimmune and allergic diseases. These electrophilic molecules interfere with intracellular signaling pathways by reversible post-translational modification of nucleophilic amino-acid residues. Several regulatory proteins have been identified as targets of NO-FAs, modifying their activity and promoting gene expression changes that result in anti-inflammatory effects. Herein, we report the effects of nitro-oleic acid (NO-OA) on pro-inflammatory T cell functions, showing that 9- and 10-NOA, but not their oleic acid precursor, decrease T cell proliferation, expression of activation markers CD25 and CD71 on the plasma membrane, and IL-2, IL-4, and IFN-γ cytokine gene expressions. Moreover, we have found that NO-OA inhibits the transcriptional activity of nuclear factor of activated T cells (NFAT) and that this inhibition takes place through the regulation of the phosphatase activity of calcineurin (CaN), hindering NFAT dephosphorylation, and nuclear translocation in activated T cells. Finally, using mass spectrometry-based approaches, we have found that NO-OA nitroalkylates CaNA on four Cys (Cys129, 228, 266, and 372), of which only nitroalkylation on Cys372 was of importance for the regulation of CaN phosphatase activity in cells, disturbing functional CaNA/CaNB heterodimer formation. These results provide evidence for an additional mechanism by which NO-FAs exert their anti-inflammatory actions, pointing to their potential as therapeutic bioactive lipids for the modulation of harmful T cell-mediated immune responses.
Topics: Mice; Animals; Calcineurin; Nitrogen Dioxide; Oleic Acid; Protein Processing, Post-Translational; Fatty Acids
PubMed: 36652486
DOI: 10.1073/pnas.2208924120