RESUMEN
Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), offer numerous health benefits. Enriching these fatty acids in fish oil using cost-effective methods, like lipase application, has been studied extensively. This research aimed to investigate F. solani as a potential lipase producer and compare its efficacy in enhancing polyunsaturated omega-3 fatty acids with commercial lipases. Submerged fermentation with coconut oil yielded Lipase F2, showing remarkable activity (215.68 U/mL). Lipase F2 remained stable at pH 8.0 (activity: 93.84 U/mL) and active between 35 and 70 °C, with optimal stability at 35 °C. It exhibited resistance to various surfactants and ions, showing no cytotoxic activity in vitro, crucial for its application in the food and pharmaceutical industries. Lipase F2 efficiently enriched EPA and DHA in fish oil, reaching 22.1 mol% DHA and 23.8 mol% EPA. These results underscore the economic viability and efficacy of Lipase F2, a partially purified enzyme obtained using low-cost techniques, demonstrating remarkable stability and resistance to diverse conditions. Its performance was comparable to highly pure commercially available enzymes in omega-3 production. These findings highlight the potential of F. solani as a promising lipase source, offering opportunities for economically producing omega-3 and advancing biotechnological applications in the food and supplements industry.
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Ácidos Grasos Omega-3 , Fusarium , Lipasa , Fusarium/enzimología , Fusarium/efectos de los fármacos , Lipasa/metabolismo , Ácidos Grasos Omega-3/metabolismo , Aceites de Pescado/metabolismo , Aceites de Pescado/química , Fermentación , Proteínas Fúngicas/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Concentración de Iones de Hidrógeno , Estabilidad de Enzimas , Aceite de Coco/química , Aceite de Coco/metabolismo , TemperaturaRESUMEN
The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.
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Ácidos Grasos Omega-3 , Hepatopatías , Humanos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Antiinflamatorios/uso terapéutico , Hepatopatías/metabolismo , Fenotipo , Mediadores de Inflamación/metabolismoRESUMEN
Background: In dogs, dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) affect the fatty acid (FA) profile of blood plasma, erythrocyte membrane (EM), and semen, but their correlation has not yet been investigated. Aim: In this study, we evaluated the association between dietary PUFA and their profile in blood plasma, EM, and semen of dogs, with the possibility to predict the semen profile using the values of the three first. Methods: Twelve male dogs received the same standard commercial diet for 4 weeks. The FA profile was analyzed by gas chromatography in paired diet, blood (plasma and EM determinations), and semen samples. Data were analyzed with SAS Proc Corr version 9.4. Pearson´s correlation coefficient (significant if p < 0.05) was used to assess the association of dietary FA profiles with those in blood plasma, EM, and semen. Results: There was a positive correlation between dietary eicosapentaenoic acid (EPA) and blood plasma (r = 0.97), EM (r = 0.94) and semen (r = 0.92) EPA, and between dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) and semen DHA (r = 0.93) and ARA (r = 0.92), respectively. There was a negative correlation between dihomo-gamma-linolenic acid (DGLA) in the diet and EM DGLA (r = -0.94). Conclusion: The dietary EPA is correlated with blood plasma, EM, and semen EPA concentrations, and dietary DHA and ARA are associated with semen DHA and ARA concentrations in dogs. These findings suggest that dietary EPA, DHA, and ARA concentrations could be helpful to predictive markers for such concentrations in the semen of dogs.
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Ácidos Grasos Omega-3 , Semen , Masculino , Perros , Animales , Semen/metabolismo , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-3/metabolismo , Dieta/veterinaria , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/metabolismo , Eritrocitos/química , Eritrocitos/metabolismo , Ácido Araquidónico/análisis , Ácido Araquidónico/metabolismo , Plasma/metabolismoRESUMEN
We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.
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Diabetes Gestacional , Neuroprostanos , Obesidad Materna , Humanos , Femenino , Embarazo , Neuroprostanos/metabolismo , Isoprostanos , Diabetes Gestacional/metabolismo , Placenta/metabolismo , F2-Isoprostanos/metabolismo , Obesidad Materna/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Araquidónico/metabolismo , Obesidad/metabolismoRESUMEN
BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. AIM: To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. SUBJECTS AND METHODS: Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. RESULTS: In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. CONCLUSIONS: EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.
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Ácidos Grasos Omega-3 , Inhibidor 1 de Activador Plasminogénico , Humanos , Inhibidor 1 de Activador Plasminogénico/metabolismo , Resistina/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacología , Autoinforme , Voluntarios Sanos , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Tejido Adiposo/metabolismo , Glucosa/metabolismoRESUMEN
Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.
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Enfermedades del Sistema Nervioso Central , Ácidos Grasos Omega-3 , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Grasos/metabolismo , Ácidos Grasos Omega-3/metabolismo , HumanosRESUMEN
Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.
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Aterosclerosis , Enfermedades Cardiovasculares , Ácidos Grasos Omega-3 , Animales , Aterosclerosis/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Inflamación/metabolismo , Mediadores de Inflamación/metabolismoRESUMEN
The incidence of cardiovascular diseases and metabolic disorders has increased worldwide. Clinical and experimental research has shown that the consumption of ω-3 FAs can be beneficial to metabolism in several ways, as they can act on metabolic pathways. Our objective was to evaluate the effect of treatment with linseed oil, a vegetable oil rich in alpha-linolenic acid, and EPA and DHA in different proportions (3:1 EPA:DHA, and 1:3 EPA:DHA), on the metabolic disorders induced by a high-fat diet (20 % lipids) in rats for 2 weeks, after 18 weeks of consumption of a high-fat diet. In 18 weeks, the high-fat diet increased blood glucose, systolic blood pressure, triglyceride concentration in the liver and adipose tissue, and impaired insulin sensibility without interfering in the weight of the animals. All treatments were effective in reducing the deposition of hepatic type III collagen, the proportion of ω-6/ω-3 in the liver and WAT (white adipose tissue), the proportion of area/number of adipocytes, and the gene expression of the ACC, FAS, and CPT1 enzymes. In addition, treatment with EPA and DHA reduced blood glucose, serum TNF-α concentration, amount of liver fat, degree of microsteatosis and type I collagen deposition in the liver, deposition of type I and III collagen in TA, gene expression of the transcription factor SREBP-1c, and increased hepatic binucleation. EPA in major proportion was more effective in reducing the area of adipocytes, hepatic triglyceride concentration, PPAR-α expression, and WAT fat weight. DHA in a major proportion reduced the concentration of MCP1 in WAT. LO treatment did not have any isolated effects. We concluded that EPA and DHA were more effective in treating metabolic damage than treatment with LO, leading to a more favorable metabolic profile.
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Dieta Alta en Grasa , Ácidos Grasos Omega-3 , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Aceite de Linaza/farmacología , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratas , Triglicéridos/metabolismoRESUMEN
In self-revolving gram-negative Escherichia coli infection, Resolvin D5 (RvD5) was found to enhance bacteria phagocytosis and reduce the production of inflammatory mediators, contributing to the resolution of infection. LPS (lipopolysaccharide) is a gram-negative bacterial structure product which activates the immune system and, at high doses, leads to endotoxemia. To our knowledge, the effect of RvD5 against LPS endotoxemia has not been investigated to date. Female Swiss mice received an i.p. treatment with RvD5 (0.1, 1 or 10 ng/animal). After 1 h, they were stimulated with LPS (10 mg/kg, i.v.), and samples were collected after additional 6 h. The resulting data demonstrated that RvD5 protected the kidneys (urea and creatinine serum levels) from tissue injury. These effects were related to an improvement in histopathological parameters and a reduction of enzymatic markers of leukocyte infiltration, pro-inflammatory cytokine (IL-1ß, TNF-α, and IL-6) production, and oxidative stress. Antioxidant markers were also increased by RvD5, but IL-10 (an anti-inflammatory cytokine) levels were unaltered. We also observed that RvD5 reduced the infiltration of CD45+ hematopoietic cells into the kidneys, reduced the activation of NFκB and promoted the Nrf2 pathway by reducing Keap-1 levels. Our data indicate that RvD5 may be a therapeutic possibility to reduce kidney lesions in LPS endotoxemia.
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Endotoxemia , Lipopolisacáridos , Femenino , Ratones , Animales , Lipopolisacáridos/toxicidad , Endotoxemia/inducido químicamente , Endotoxemia/tratamiento farmacológico , Riñón , Ácidos Docosahexaenoicos/metabolismoRESUMEN
The psychrophilic marine microorganism Thraustochytrium sp. RT2316-16 can produce carotenoids as well as lipids containing the omega-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid and docosahexaenoic acid. This work reports on the effects of the composition of the culture medium, including certain amino acids, on growth and lipid synthesis by RT2316-16. Compared with the culture on glutamate, the use of lysine, alanine, or serine, increased the content of the omega-3 PUFA in total lipids. In the media that contained yeast extract, glutamate, and glucose, lipid accumulation occurred when organic ammonium was exhausted earlier than glucose. In contrast, lipid mobilization was promoted if glucose was exhausted while organic ammonium (supplied by yeast extract and glutamate) remained in the medium. The total content of carotenoids in the lipid-free biomass decreased during the first 12 to 24 h of culture, simultaneously with a decrease in the total lipid content of the biomass. The experimental data suggested a possible interrelationship between the metabolism of carotenoids and lipids. A high content of omega-3 PUFA in the total lipids could be obtained by growing the thraustochytrid in a medium with a low glucose concentration (6 g L-1) and a high concentration of organic nitrogen (yeast extract 12 g L-1; glutamate 1.06 g L-1), after glucose was exhausted. These observations may guide the development of a strategy to enhance omega-3 PUFA in the biomass.
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Ácidos Grasos Omega-3 , Estramenopilos , Nitrógeno/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Estramenopilos/metabolismo , Carotenoides/metabolismo , Glucosa/metabolismo , Glutamatos/metabolismo , Ácidos Grasos/metabolismoRESUMEN
Modern western diets have been associated with a reduced proportion of dietary omega-3 fatty acids leading to decreased levels of DHA (docosahexaenoic acid) in the brain. Low DHA content has been associated with altered development of visual acuity in infants and also with an altered time course of synapse elimination and plasticity in subcortical visual nuclei in rodents. Microglia has an active role in normal developmental processes such as circuitry refinement and plasticity, and its activation status can be modulated by omega-3 (ω3) and omega-6 (ω6) essential fatty acids. In the present study, we investigated the impact of dietary restriction of DHA (ω3-), through the chronic administration of a coconut-based diet as the only fat source. This dietary protocol resulted in a reduction in DHA content in the retina and superior colliculus (SC) and in a neuroinflammatory outcome during the development of the rodent visual system. The ω3- group showed changes in microglial morphology in the retina and SC and a corresponding altered pattern of pro-inflammatory cytokine expression. Early and late fish oil protocols supplementation were able to restore DHA levels. The early supplementation also decreased neuroinflammatory markers in the visual system. The present study indicates that a chronic dietary restriction of omega-3 fatty acids and the resulting deficits in DHA content, commonly observed in Western diets, interferes with the microglial profile leading to an inflamed microenvironment which may underlie a disruption of synapse elimination, altered topographical organization, abnormal plasticity, and duration of critical periods during brain development.
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Ácidos Grasos Omega-3/metabolismo , Inflamación/etiología , Visión Ocular/fisiología , Animales , Animales Recién Nacidos , Dieta , Ácidos Docosahexaenoicos/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Aceites de Pescado/uso terapéutico , Microglía , Enfermedades Neuroinflamatorias/etiología , Ratas , Retina/crecimiento & desarrollo , Retina/metabolismo , Colículos Superiores/crecimiento & desarrollo , Colículos Superiores/metabolismo , Agudeza VisualRESUMEN
This work investigates how docosahexaenoic acid (DHA) modifies the effect of Cholesterol (Chol) on the structural and dynamical properties of dipalmitoylphosphatidylcholine (DPPC) membrane. We employ low-cost and non-invasive methods: zeta potential (ZP), conductivity, density, and ultrasound velocity, complemented by molecular dynamics simulations. Our studies reveal that 30% of DHA added to the DPPC-Chol system tends to revert Chol action on a model lipid bilayer. Results obtained in this work shed light on the effect of polyunsaturated fatty acids - particularly DHA - on lipid membranes, with potential preventive applications in many diseases, e.g. neuronal as, Alzheimer's disease, and viral, as Covid-19.
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Colesterol/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Membrana Dobles de Lípidos/metabolismo , Fosfatidilcolinas/metabolismo , Liposomas , Estructura Molecular , Temperatura , Ondas UltrasónicasRESUMEN
To improve the oral absorption of fish oil and test its anti-inflammatory effect, a fish oil nanoemulsion was developed using cis-4,7,10,13,16,19-docosahexaenoic fatty acid as a biomarker for oral administration. The colloidal stability tests of the fish oil nanoemulsion showed an average size of 155.44â¯nm⯱â¯6.46 (4⯰C); 163.04â¯nm⯱â¯9.97 (25⯰C) and polydispersity index 0.22⯱â¯0.02 (4⯰C), 0.21⯱â¯0.02 (25⯰C), indicating systems with low polydispersity and stable droplets. The fish oil nanoemulsion did not alter the cell viability of the RAW 264.7 macrophages and, at a concentration of 0.024â¯mg/mL, was kinetically incorporated into the cells after 18â¯h of contact. The nanoemulsion was maintained in the gastrointestinal region for a significantly shorter period of time (pâ¯≤â¯0.05) compared to the intake of fish oil in free form. Inflammatory tests demonstrated that nanoemulsion and fish oil showed less (pâ¯≤â¯0.05) neutrophil infiltration after 24h of sepsis induction and there was a significant reduction (pâ¯≤â¯0.05) in the volume of paw edema in female adult Balb/c mice who received the nanoemulsion diet compared to the other experimental groups (control, formalin, fish oil and sunflower oil). These results indicate that the fish oil nanoemulsion was significantly effective in the dietary conditions tested here, presenting satisfactory responses in the modulation of inflammatory disorders, demonstrating interesting and beneficial nutraceutical effects.
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Antiinflamatorios/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Edema/prevención & control , Ácido Eicosapentaenoico/administración & dosificación , Inflamación/prevención & control , Nanopartículas , Agua/química , Administración Oral , Animales , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/metabolismo , Combinación de Medicamentos , Composición de Medicamentos , Estabilidad de Medicamentos , Edema/inmunología , Edema/metabolismo , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/metabolismo , Emulsiones , Femenino , Vaciamiento Gástrico , Inflamación/inmunología , Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Infiltración Neutrófila/efectos de los fármacos , Tamaño de la Partícula , Células RAW 264.7RESUMEN
Human embryonic kidney (HEK) 293 cells were co-transfected with plasmids for the expression of mCherry fluorescent protein-tagged FFA4 receptors and the enhanced green fluorescent protein-tagged Rab proteins involved in retrograde transport and recycling, to study their possible interaction through Förster Resonance Energy Transfer (FRET), under the action of agents that induce FFA4 receptor phosphorylation and internalization through different processes, i.e., the agonist, docosahexaenoic acid, the protein kinase C activator phorbol myristate acetate, and insulin. Data indicate that FFA4 receptor internalization varied depending on the agent that induced the process. Agonist activation (docosahexaenoic acid) induced an association with early endosomes (as suggested by interaction with Rab5) and rapid recycling to the plasma membrane (as indicated by receptor interaction with Rab4). More prolonged agonist stimulation also appears to allow the FFA4 receptors to interact with late endosomes (interaction with Rab9), slow recycling (interaction with Rab 11), and target to degradation (Rab7). Phorbol myristate acetate, triggered a rapid association with early endosomes (Rab5), slow recycling to the plasma membrane (Rab11), and some receptor degradation (Rab7). Insulin-induced FFA4 receptor internalization appears to be associated with interaction with early endosomes (Rab5) and late endosomes (Rab9) and fast and slow recycling to the plasma membrane (Rab4, Rab11). Additionally, we observed that agonist- and PMA-induced FFA4 internalization was markedly reduced by paroxetine, which suggests a possible role of G protein-coupled receptor kinase 2.
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Ácidos Docosahexaenoicos/metabolismo , Insulina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Acetato de Tetradecanoilforbol/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Ácidos Docosahexaenoicos/farmacología , Células HEK293 , Humanos , Insulina/farmacología , Unión Proteica/efectos de los fármacos , Unión Proteica/fisiología , Isoformas de Proteínas/metabolismo , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Prostate cancer (PCa) has different molecular features along progression, including androgen profile, which is associated to therapy inefficiency leading to more aggressive phenotype. Docosahexaenoic acid (DHA) has antiproliferative and pro-apoptotic properties in different cancers associated to cell metabolism modulation. The latter is of particular interest since metabolic reprogramming is one of PCa hallmarks, but is not clear how this occurs among disease progression. Therefore, we evaluated DHA antiproliferative potential in distinct androgenic backgrounds associated to metabolism modulation and androgen-regulated genes. For this purpose, pre-malignant PNT1A and tumor AR-positive 22rv1, and AR-negative PC3 cells were incubated with DHA at 100 µM-48 h. DHA reduced at least 26% cell number for all lineages due to S-phase decrease in AR-positive and G2/M arrest in AR-negative. Mitochondrial metabolic rate decreased in PNT1A (~38%) and increased in tumor cells (at least 40%). This was associated with ROS overproduction (1.6-fold PNT1A; 2.1 22rv1; 2.2 PC3), lipid accumulation (3-fold PNT1A; 1.8 22rv1; 3.6 PC3) and mitochondria damage in all cell lines. AKT, AMPK and PTEN were not activated in any cell line, but p-ERK1/2 increased (1.5-fold) in PNT1A. Expression of androgen-regulated and nuclear receptors genes showed that DHA affected them in a distinct pattern in each cell line, but most converged to metabolism regulation, response to hormones, lipids and stress. In conclusion, regardless of androgenic or PTEN background DHA exerted antiproliferative effect associated to cell cycle impairment, lipid deregulation and oxidative stress, but differentially regulated gene expression probably due to distinct molecular features of each pathologic stage.
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Ciclo Celular/genética , Ácidos Docosahexaenoicos/metabolismo , Redes y Vías Metabólicas/genética , Próstata/metabolismo , Neoplasias de la Próstata/genética , Andrógenos/genética , Andrógenos/metabolismo , Apoptosis/genética , División Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Redes Reguladoras de Genes/genética , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1ß, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.
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Dermatitis/prevención & control , Ácidos Heptanoicos/administración & dosificación , Protectores contra Radiación/administración & dosificación , Receptores de Lipoxina/antagonistas & inhibidores , Animales , Antígenos CD59/metabolismo , Dermatitis/etiología , Dermatitis/metabolismo , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/metabolismo , Relación Dosis-Respuesta a Droga , Ácidos Heptanoicos/farmacología , Lipoxinas/metabolismo , Ratones , Ratones Pelados , Protectores contra Radiación/farmacología , Rayos Ultravioleta/efectos adversosRESUMEN
Production of biomass and lipids in batch cultures of the Antarctic thraustochytrid Oblongichytrium sp. RT2316-13, is reported. The microorganism proved capable of producing nearly 67% docosahexaenoic acid (DHA) and 15% eicosapentaenoic acid (EPA) in its total lipid fraction. Biomass with a maximum total lipid content of 33.5% (wt/wt) could be produced at 15°C in batch culture using a medium containing glucose (20 g/L), yeast extract (10.5 g/L), and other minor components. A lower culture temperature (5°C) reduced biomass and lipid productivities compared to culture at 15°C, but enhanced the DHA and EPA content of the lipids by 6.4- and 3.3-fold, respectively. Both a simple minimally structured mathematical model and a more complex genome-scale metabolic model (GEM) allowed the fermentation profiles in batch cultures to be satisfactorily simulated, but the GEM provided much greater insight in the biochemical and physiological phenomena underlying the observed behavior. Unlike the simpler model, the GEM could be interrogated for the possible effects of various external factors such as oxygen supply, on the expected outcomes. In silico predictions of oxygen effects were consistent with literature observations for DHA producing thraustochytrids.
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Organismos Acuáticos/metabolismo , Biotecnología/métodos , Medios de Cultivo/química , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Fermentación , Estramenopilos/metabolismo , Regiones Antárticas , Organismos Acuáticos/crecimiento & desarrollo , Organismos Acuáticos/aislamiento & purificación , Biomasa , Frío , Ácidos Docosahexaenoicos/análisis , Ácido Eicosapentaenoico/análisis , Estramenopilos/crecimiento & desarrollo , Estramenopilos/aislamiento & purificaciónRESUMEN
Resveratrol (Resv) offers health benefits in cancer and has been reported to modulate important enzymes of lipid metabolism. Studies of its effects on lipid composition in different subtypes of breast-cancer cells are scarce. Thus, we investigated the alterations in phospholipids (PL), fatty acids (FA), and lipid metabolism enzymes in two breast-cancer cell lines after Resv treatment. MCF-7 and MDA-MB-231 cells were treated with 80 and 200 µM of Resv, respectively, for 24 hours. We analyzed PL with radiolabeled inorganic phosphate (32Pi) by thin-layer chromatography, FA by gas chromatography-mass spectrometry, and lipid metabolism enzymes (DGAT2, FAS, ρACCß, pAMPKα, and AMPK) by Western blot. Resv treated MDA-MB-231 phospholipids showed a reduction in phosphatidylcholine (63%) and phosphatidylethanolamine (35%). We observed an increase in eicosapentaenoic acid (EPA) (73%) and docosahexaenoic acid (DHA) (65%) in MCF-7 cells after Resv treatment. Interestingly, the same treatment caused 50% and 90% increases in EPA and DHA, respectively, in MDA-MB-231 cells. In MCF-7 cells, Resv increased the expression of ρACCß (3.3-fold) and AMPKα/ρAMPKα (1.5-fold) and in MDA-MB-231 cells it inhibited the expression of ρACCß (111.8-fold) and AMPKα/ρAMPKα (1.2 fold). Our results show that Resv modified PL and saturated and unsaturated FA especially in MDA-MB-231 cells, and open new perspectives to the understanding of the reported anticancer effect of Resv on these cells.
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Neoplasias de la Mama/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Resveratrol/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Grasos/metabolismo , Ácidos Grasos Insaturados , Femenino , Humanos , Lípidos/análisis , Células MCF-7 , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfolípidos/metabolismo , Resveratrol/uso terapéuticoRESUMEN
High-fat diet (HFD)-fed mice show obesity with development of liver steatosis and a proinflammatory state without establishing an inflammatory reaction. The aim of this work was to assess the hypothesis that eicosapentaenoic acid (EPA) plus hydroxytyrosol (HT) supplementation prevents the inflammatory reaction through enhancement in the hepatic resolvin content in HFD-fed mice. Male C57BL/6J mice were fed an HFD or a control diet and supplemented with EPA (50 mg/kg/day) and HT (5 mg/kg/day) or their respective vehicles for 12 weeks. Measurements include liver levels of EPA, DHA and palmitate (gas chromatography), liver resolvins and triglyceride (TG) and serum aspartate transaminase (AST) (specific kits) and hepatic and serum inflammatory markers (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). Compared to CD, HFD induced body weight gain, liver steatosis and TG accumulation, with up-regulation of proinflammatory markers in the absence of histological inflammation or serum AST changes; these results were accompanied by higher hepatic levels of resolvins RvE1, RvE2, RvD1 and RvD2, with decreases in EPA and DHA contents. EPA+HT supplementation in HFD feeding synergistically reduced the steatosis score over individual treatments and increased the hepatic levels of EPA, DHA and resolvins, with attenuation of proinflammatory markers. Lack of progression of HFD-induced proinflammatory state into overt inflammation is associated with resolvin up-regulation, which is further increased by EPA+HT supplementation eliciting steatosis attenuation. These findings point to the importance of combined protocols in hepatoprotection due to the involvement of cross-talk mechanisms, which increase effectiveness and diminish dosages, avoiding undesirable effects.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Ácido Eicosapentaenoico/farmacología , Hepatitis/dietoterapia , Hígado/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Animales , Suplementos Dietéticos , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos/metabolismo , Hepatitis/etiología , Hepatitis/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Alcohol Feniletílico/farmacologíaRESUMEN
In vertebrates, the essential fatty acids (FA) that satisfy the dietary requirements for a given species depend upon its desaturation and elongation capabilities to convert the C18 polyunsaturated fatty acids (PUFA), namely linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), into the biologically active long-chain (C20-24) polyunsaturated fatty acids (LC-PUFA), including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Recent studies have established that tambaqui (Colossoma macropomum), an important aquaculture-produced species in Brazil, is a herbivorous fish that can fulfil its essential FA requirements with dietary provision C18 PUFA LA and ALA, although the molecular mechanisms underpinning such ability remained unclear. The present study aimed at cloning and functionally characterizing genes encoding key desaturase and elongase enzymes, namely fads2, elovl5 and elovl2, involved in the LC-PUFA biosynthetic pathways in tambaqui. First, a fads2-like desaturase was isolated from tambaqui. When expressed in yeast, the tambaqui Fads2 showed Δ6, Δ5 and Δ8 desaturase capacities within the same enzyme, enabling all desaturation reactions required for ARA, EPA and DHA biosynthesis. Moreover, tambaqui possesses two elongases that are bona fide orthologs of elovl5 and elovl2. Their functional characterization confirmed that they can operate towards a variety of PUFA substrates with chain lengths ranging from 18 to 22 carbons. Overall our results provide compelling evidence that demonstrates that all the desaturase and elongase activities required to convert LA and ALA into ARA, EPA and DHA are present in tambaqui within the three genes studied herein, i.e. fads2, elovl5 and elovl2.