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1.
Cell ; 179(6): 1289-1305.e21, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31761534

RESUMO

Adult mesenchymal stem cells, including preadipocytes, possess a cellular sensory organelle called the primary cilium. Ciliated preadipocytes abundantly populate perivascular compartments in fat and are activated by a high-fat diet. Here, we sought to understand whether preadipocytes use their cilia to sense and respond to external cues to remodel white adipose tissue. Abolishing preadipocyte cilia in mice severely impairs white adipose tissue expansion. We discover that TULP3-dependent ciliary localization of the omega-3 fatty acid receptor FFAR4/GPR120 promotes adipogenesis. FFAR4 agonists and ω-3 fatty acids, but not saturated fatty acids, trigger mitosis and adipogenesis by rapidly activating cAMP production inside cilia. Ciliary cAMP activates EPAC signaling, CTCF-dependent chromatin remodeling, and transcriptional activation of PPARγ and CEBPα to initiate adipogenesis. We propose that dietary ω-3 fatty acids selectively drive expansion of adipocyte numbers to produce new fat cells and store saturated fatty acids, enabling homeostasis of healthy fat tissue.


Assuntos
Adipogenia , Cílios/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Fator de Ligação a CCCTC/metabolismo , Cromatina/metabolismo , Cílios/efeitos dos fármacos , AMP Cíclico/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo
2.
Hepatology ; 77(4): 1303-1318, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35788956

RESUMO

BACKGROUND AND AIM: Injury to hepatocyte mitochondria is common in metabolic dysfunction-associated fatty liver disease. Here, we investigated whether changes in the content of essential fatty acid-derived lipid autacoids affect hepatocyte mitochondrial bioenergetics and metabolic efficiency. APPROACH AND RESULTS: The study was performed in transgenic mice for the fat-1 gene, which allows the endogenous replacement of the membrane omega-6-polyunsaturated fatty acid (PUFA) composition by omega-3-PUFA. Transmission electron microscopy revealed that hepatocyte mitochondria of fat-1 mice had more abundant intact cristae and higher mitochondrial aspect ratio. Fat-1 mice had increased expression of oxidative phosphorylation complexes I and II and translocases of both inner (translocase of inner mitochondrial membrane 44) and outer (translocase of the outer membrane 20) mitochondrial membranes. Fat-1 mice also showed increased mitofusin-2 and reduced dynamin-like protein 1 phosphorylation, which mediate mitochondrial fusion and fission, respectively. Mitochondria of fat-1 mice exhibited enhanced oxygen consumption rate, fatty acid ß-oxidation, and energy substrate utilization as determined by high-resolution respirometry, [1- 14 C]-oleate oxidation and nicotinamide adenine dinucleotide hydride/dihydroflavine-adenine dinucleotide production, respectively. Untargeted lipidomics identified a rich hepatic omega-3-PUFA composition and a specific docosahexaenoic acid (DHA)-enriched lipid fingerprint in fat-1 mice. Targeted lipidomics uncovered a higher content of DHA-derived lipid autacoids, namely resolvin D1 and maresin 1, which rescued hepatocytes from TNFα-induced mitochondrial dysfunction, and unblocked the tricarboxylic acid cycle flux and metabolic utilization of long-chain acyl-carnitines, amino acids, and carbohydrates. Importantly, fat-1 mice were protected against mitochondrial injury induced by obesogenic and fibrogenic insults. CONCLUSION: Our data uncover the importance of a lipid membrane composition rich in DHA and its lipid autacoid derivatives to have optimal hepatic mitochondrial and metabolic efficiency.


Assuntos
Ácidos Graxos Ômega-3 , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Conservação de Recursos Energéticos , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Mitocôndrias/metabolismo , Ácidos Graxos Ômega-6/química , Ácidos Graxos Ômega-6/metabolismo , Ácidos Graxos Ômega-6/farmacologia , Camundongos Transgênicos , Ácidos Graxos/metabolismo
3.
Eur J Clin Invest ; 54(2): e14109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37859571

RESUMO

INTRODUCTION: N-3 polyunsaturated fatty acids (PUFAs) supplementation has been reported to have an impact on flow-mediated dilatation (FMD), a conventionally used clinical technique for estimating endothelial dysfunction. However, its proven effects on endothelial function are unclear. This systematic review and meta-analysis were conducted to evaluate the effects of n-3 PUFAs supplementation on FMD of the brachial artery. METHOD: This study was performed following the PRISMA guidelines. To identify eligible RCTs, a systematic search was completed in PubMed/Medline, Scopus and Web of Science using relevant keywords. A fixed- or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). RESULTS: Thirty-two studies (with 35 arms) were included in this meta-analysis, involving 2385 subjects with intervention duration ranging from 4 to 48 weeks. The pooled meta-analysis demonstrated a significant effect of omega-3 on FMD (WMD = 0.8%, 95% CI = 0.3-1.3, p = .001) and heterogeneity was significant (I2 = 82.5%, p < .001). CONCLUSION: We found that n-3 PUFA supplementation improves endothelial function as estimated by flow-mediated dilatation of the brachial artery.


Assuntos
Ácidos Graxos Ômega-3 , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Endotélio Vascular , Artéria Braquial/diagnóstico por imagem , Suplementos Nutricionais
4.
Haematologica ; 109(6): 1918-1932, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105727

RESUMO

Inflammatory vasculopathy is critical in sickle cell disease (SCD)-associated organ damage. An imbalance between pro-inflammatory and pro-resolving mechanisms in response to different triggers such as hypoxia/reoxygenation or infections has been proposed to contribute to the progression of SCD. Administration of specialized pro-resolving lipid mediators may provide an effective therapeutic strategy to target inflammatory vasculopathy and to modulate inflammatory response. Epeleuton (15 hydroxy eicosapentaenoic acid ethyl ester) is a novel, orally administered, second-generation ω-3 fatty acid with a favorable clinical safety profile. In this study we show that epeleuton re-programs the lipidomic pattern of target organs for SCD towards a pro-resolving pattern. This protects against systemic and local inflammatory responses and improves red cell features, resulting in reduced hemolysis and sickling compared with that in vehicle-treated SCD mice. In addition, epeleuton prevents hypoxia/reoxygenation-induced activation of nuclear factor-κB with downregulation of the NLRP3 inflammasome in lung, kidney, and liver. This was associated with downregulation of markers of vascular activation in epeleuton-treated SCD mice when compared to vehicle-treated animals. Collectively our data support the potential therapeutic utility of epeleuton and provide the rationale for the design of clinical trials to evaluate the efficacy of epeleuton in patients with SCD.


Assuntos
Anemia Falciforme , Modelos Animais de Doenças , Traumatismo por Reperfusão , Animais , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Anemia Falciforme/complicações , Camundongos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Humanos , Masculino , Hipóxia/metabolismo , Hipóxia/tratamento farmacológico
5.
J Nutr ; 154(2): 395-402, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38081585

RESUMO

BACKGROUND: Oxylipins are products derived from polyunsaturated fatty acids (PUFAs) that play a role in cardiovascular disease and aging. Fish oil-derived n-3 PUFAs promote the formation of anti-inflammatory and vasodilatory oxylipins; however, there are little data on oxylipins derived from α-linolenic acid (C18:3n-3), the primary plant-derived n-3 PUFA. Walnuts are a source of C18:3n-3. OBJECTIVES: To investigate the effect on serum oxylipins of a diet enriched with walnuts at 15% energy (30-60 g/d; 2.6-5.2 g C18:3n-3/d) for 2 y compared to a control diet (abstention from walnuts) in healthy older males and females (63-79 y). METHODS: The red blood cell proportion of α-linolenic acid was determined by gas chromatography as a measure of compliance. Ultra-performance liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 53 oxylipins in participants randomly assigned to receive the walnut diet (n = 64) or the control diet (n = 51). Two-year concentration changes (final minus baseline) were log-transformed (base log-10) and standardized (mean-centered and divided by the standard deviation of each variable). Volcano plots were then generated (fold change ≥1.5; false discovery rate ≤0.1). For each oxylipin delta surviving multiple testing, we further assessed between-intervention group differences by analysis of covariance adjusting for age, sex, BMI, and the baseline concentration of the oxylipin. RESULTS: The 2-y change in red blood cell C18:3n-3 in the walnut group was significantly higher than that in the control group (P < 0.001). Compared to the control diet, the walnut diet resulted in statistically significantly greater increases in 3 C18:3n-3-derived oxylipins (9-HOTrE, 13-HOTrE, and 12,13-EpODE) and in the C20:5n-3 derived 14,15-diHETE, and greater reductions of the C20:4n-6-derived 5-HETE, 19-HETE, and 5,6-diHETrE. CONCLUSIONS: Long-term walnut consumption changes the serum oxylipin profile in healthy older persons. Our results add novel mechanistic evidence on the cardioprotective effects of walnuts. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01634841.


Assuntos
Ácidos Graxos Ômega-3 , Juglans , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Oxilipinas , Ácido alfa-Linolênico , Dieta , Ácidos Graxos Insaturados , Ácidos Graxos Ômega-3/farmacologia
6.
Brain Behav Immun ; 115: 335-355, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914102

RESUMO

Alzheimer's disease (AD) and other forms of dementia represent major public health challenges but effective therapeutic options are limited. Pathological brain aging is associated with microvascular changes and impaired clearance systems. The application of omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) is one of the most promising nutritional interventions in neurodegenerative disorders from epidemiological data, clinical and pre-clinical studies. As essential components of neuronal membranes, n-3 PUFAs have shown neuroprotection and anti-inflammatory effects, as well as modulatory effects through microvascular pathophysiology, amyloid-beta (Aß) clearance and glymphatic pathways. This review meticulously explores these underlying mechanisms that contribute to the beneficial effects of n-3 PUFAs against AD and dementia, synthesizing evidence from both animal and interventional studies.


Assuntos
Doença de Alzheimer , Ácidos Graxos Ômega-3 , Animais , Barreira Hematoencefálica/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Encéfalo/metabolismo , Doença de Alzheimer/metabolismo
7.
Neurochem Res ; 49(1): 157-169, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37640824

RESUMO

Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.


Assuntos
Delírio do Despertar , Ácidos Graxos Ômega-3 , Humanos , Camundongos , Animais , Idoso , Óleos de Peixe , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Doenças Neuroinflamatórias , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Anti-Inflamatórios/farmacologia
8.
Nutr Cancer ; 76(1): 1-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37897076

RESUMO

Until now, no study evaluated the impact of optimum intake of omega-3 fatty acids on inflammatory factors. We aimed to investigate the dose-dependent effects of omega-3 fatty acids supplementation on inflammatory factors in cancer patients. PubMed, Scopus and ISI Web of Science were searched until July 2022 to find randomized controlled trials (RCTs) for examining the efficacy of omega-3 fatty acids on inflammatory factors. Our primary outcomes were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and albumin. The results of 33 trials (2068 participants) revealed that each 1 g/day omega-3 fatty acids (oral/enteral) significantly reduced IL-6 (SMD: -1.17 pg/ml; 95% CI: -1.78, -0.55; p < 0.001; GRADE = moderate), and TNF-α (SMD: -2.15 pg/ml; 95% CI: -3.14, -1.16; p < 0.001; GRADE = very low). Moreover, each 0.5 g/kg/day omega-3 fatty acids (parenteral) significantly reduced TNF-α (SMD: -1.11 pg/ml; 95% CI: -2.02, -0.19; p = 0.017; GRADE = low). With moderate and very low evidence certainty, each 1 g/day of omega-3 fatty acids supplementation (oral/enteral) has a beneficial effect on IL-6 and TNF-α. Each 0.5 g/kg/day omega-3 fatty acids (parenteral) could also exert a favorable impact on TNF-α, but the certainty of the evidence was low.


Assuntos
Ácidos Graxos Ômega-3 , Neoplasias , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa , Suplementos Nutricionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias/tratamento farmacológico , Inflamação/tratamento farmacológico
9.
Prostaglandins Other Lipid Mediat ; 170: 106799, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37977351

RESUMO

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis pose substantial public health challenges. While genetics play a primary role, recent research emphasizes the impact of environmental factors, particularly diet and lifestyle. This study investigates the initiating effects of Omega (ω)- 3 and Omega (ω)- 6 fatty acids on neuroinflammation, potentially contributing to these diseases. Using BV-2 microglial cells, we explored the influence of different fatty acid compositions and ratios on cell viability, cytokine production, morphological changes, and lipid peroxidation. Notably, a 2/1 ω-6:ω-3 ratio led to decreased cell viability. Fatty acid compositions influenced cytokine secretion, with reduced TNF-α suggesting anti-inflammatory effects. IL-17 increased, while IL-4 and IL-10 decreased in the 15/1 ω-6:ω-3 ratio, indicating complex cytokine interactions. This study found that polyunsaturated fatty acids interventions induced microglial activation, altering cell morphology even without immunostimulants. These findings demonstrate the intricate nature of fatty acid interactions with microglial cells and their potential implications for neuroinflammation. Further research is needed to clarify mechanisms and their relevance to neurodegenerative diseases, informing possible therapeutic strategies.


Assuntos
Ácidos Graxos Ômega-3 , Doenças Neurodegenerativas , Humanos , Ácidos Graxos , Doenças Neuroinflamatórias , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Citocinas , Doenças Neurodegenerativas/tratamento farmacológico
10.
Br J Nutr ; 131(5): 841-850, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-37886879

RESUMO

Several meta-analyses investigating the efficacy of n-3 PUFA in alleviating depression symptoms have reported conflicting findings. In the present study, we aimed to perform an umbrella meta-analysis to provide a definite conclusion. A comprehensive systematic search of PubMed, Scopus, Embase, Web of Science and Cochrane Central Library was performed up to June 2021. Meta-analysis studies evaluating the effects of n-3 PUFA on depression symptoms were included. The quality of the included meta-analyses was assessed using AMSTAR questionnaire. Out of 101 studies, twenty-two studies with twenty-six effect sizes (ES) were eligible for inclusion. Sixteen ES showed significant improving effect of n-3 supplementation on depression symptoms among which eleven ES had small ES. The other studies observed no significant effect. Available evidence suggests that n-3 PUFA (EPA, DHA) supplementation could be considered as an effective add-on therapeutic approach in relieving depression symptoms.


Assuntos
Depressão , Ácidos Graxos Ômega-3 , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Inquéritos e Questionários , Suplementos Nutricionais
11.
Br J Nutr ; 131(5): 749-761, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-37877265

RESUMO

Long-chain n-3 PUFA (LC n-3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZOFO), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycaemic-hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZOFO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.


Assuntos
Ácidos Graxos Ômega-3 , Resistência à Insulina , Humanos , Masculino , Ratos , Animais , Resistência à Insulina/fisiologia , Óleos de Peixe/farmacologia , Ratos Zucker , Glicemia/metabolismo , Insulina/metabolismo , Obesidade/metabolismo , Glucose/farmacologia , Ingestão de Alimentos , Aumento de Peso , Ácidos Graxos Insaturados/farmacologia , Óleo de Milho/farmacologia , Ácidos Graxos Ômega-3/farmacologia
12.
Org Biomol Chem ; 22(14): 2877-2890, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38525805

RESUMO

Oxidative stress and carbonyl stress resulting from the toxicity of small aldehydes are part of the detrimental mechanisms leading to neuronal cell loss involved in the progression of neurodegenerative diseases such as Alzheimer's disease. Polyunsaturated alkylated lipophenols represent a new class of hybrid molecules that combine the health benefits of anti-inflammatory omega-3 fatty acids with the anti-carbonyl and oxidative stress (anti-COS) properties of (poly)phenols in a single pharmacological entity. To investigate the therapeutic potential of quercetin-3-docosahexaenoic acid-7-isopropyl lipophenol in neurodegenerative diseases, three synthetic pathways using chemical or chemo-enzymatic strategies were developed to access milligram or gram scale quantities of this alkyl lipophenol. The protective effect of quercetin-3-DHA-7-iPr against cytotoxic concentrations of acrolein (a carbonyl stressor) was assessed in human SHSY-5Y neuroblastoma cells to underscore its ability to alleviate harmful mechanisms associated with carbonyl stress in the context of neurodegenerative diseases.


Assuntos
Ácidos Graxos Ômega-3 , Doenças Neurodegenerativas , Humanos , Quercetina/farmacologia , Estresse Oxidativo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo
13.
Crit Care ; 28(1): 38, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302945

RESUMO

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.


Assuntos
Ácido Eicosapentaenoico , Ácidos Graxos Ômega-3 , Humanos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Estado Terminal/terapia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Inflamação/tratamento farmacológico , Músculo Esquelético , Proteínas Musculares
14.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 171-177, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836663

RESUMO

Chronic heart disease (CHD) is still a major global cause of morbidity and mortality, necessitating effective therapeutic interventions to mitigate its progression. Omega-3 fatty acids (FAs) have garnered attention for their potential anti-inflammatory and endothelial-protective properties in CHD management. The present study aims to assess the efficacy of Omega-3 FA supplementation on markers of inflammation and endothelial function in patients with CHD. To achieve this, we used the relevant keywords to search international databases (Web of Science, PubMed, Embase, and Scopus) and extract publications evaluating the effectiveness of omega-3 FA supplementation on inflammation markers and endothelial function in patients with CHD. STATA (version 15) and the random and fixed-effects models were used to evaluate the collected data. Thirteen clinical trial studies met inclusion criteria, with a total sample size of 853 individuals (406 cases and 447 controls). The cases had a mean age of 58 ± 10.3 years. The pooled results indicated that omega-3 Omega-3 FA supplementation significantly reduced the level of circulating IL-6 (SMD = -0.47, 95% CI -1.29 to 0.35, %, p < 0.001), hs-CRP (SMD = -0.21, 95% CI -0.70 to 0.28, p = 0.01), and TNF-α (SMD = -0.56, 95% CI -1.14 to 0.01, p < 0.001) in patients with CHD. Also, findings revealed that a daily supplement of omega-3 significantly increased FMD by 0.34% (95% CI: 0.14-0.54%, p < 0.001) as compared with placebo by a fixed-effect model in patients with CHD. These findings underscore the potential therapeutic utility of omega-3 fatty acid supplementation in modulating inflammation and endothelial dysfunction in patients with CHD.


Assuntos
Biomarcadores , Suplementos Nutricionais , Ácidos Graxos Ômega-3 , Inflamação , Humanos , Pessoa de Meia-Idade , Biomarcadores/sangue , Doença Crônica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Cardiopatias/tratamento farmacológico , Cardiopatias/sangue , Inflamação/tratamento farmacológico , Inflamação/sangue , Idoso
15.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 107-112, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678615

RESUMO

Parkinson's disease (PD) is defined as a progressive neurodegenerative disease in middle-aged and elderly people. The therapeutic effect of ω-3 PUFAs in several neurodegenerative diseases has been well recognized. Nevertheless, whether nutrition supplementing ω-3 PUFAs exerts a neuroprotective role in PD remains elusive. Bioinformatics revealed 2D chemical structural formula of three components. Mice received indicated treatment with saline, MPTP or ω-3 PUFAs according to grouping. Behavioral function of mice was measured through motor tests such as rearing, akinesia, and rotarod tests. OFT test measured anxiety-like behaviors of mice. Western blotting and TUNEL staining measured dopaminergic fibers and neurons of mice. Western blotting measured inflammation and apoptosis-related protein levels in mouse tissue. FACS measured iTreg cell proportion in colon and brain tissues of mice. ω-3 PUFAs repaired MPTP-stimulated motor function damage in PD mice. ω-3 PUFAs mitigated MPTP-stimulated comorbid anxiety in PD mice. ω-3 PUFAs relieved MPTP-stimulated deficits of dopaminergic fibers and neurons in PD mice. ω-3 PUFAs repressed MPTP-stimulated inflammation and apoptosis pathway activation in PD mice. ω-3 PUFAs repaired MPTP-stimulated immune function damage in PD mice. ω-3 PUFAs exert a protective role in PD mice through alleviating motor function impairment and neuroinflammation by increasing intestinal inducible Treg cells, which may provide a new direction for seeking targeted therapy plans for PD in humans.


Assuntos
Modelos Animais de Doenças , Ácidos Graxos Ômega-3 , Camundongos Endogâmicos C57BL , Doença de Parkinson , Linfócitos T Reguladores , Animais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Camundongos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Masculino , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Intestinos/efeitos dos fármacos , Intestinos/patologia , Comportamento Animal/efeitos dos fármacos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Inflamação/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo
16.
Nutr Neurosci ; 27(2): 172-183, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36657165

RESUMO

ABSTRACTObjetives: Omega-3 (n3) fatty acids have been studied as an option to alleviate the harmful effects of obesity. However, its role in obesity-related behavioral changes is still controversial. This study aimed to evaluate the effects of n3 on behavior and neuroinflammation in obese animals. Methods: Male Wistar rats were divided into four groups: control diet (CT), CT+n3, cafeteria diet (CAF), and CAF+n3. Diet was administered for 13 weeks, and n3 was supplemented during the last 5 weeks. Metabolic and biochemical parameters were evaluated, as well as anxiety-like behaviors. Immunoblots were conducted in the animals' cerebral cortex and hippocampus to assess changes in neuroinflammatory markers.Results: CAF-fed animals showed higher weight gain, visceral adiposity, fasting glucose, total cholesterol, triglycerides, and insulin levels, and n3 improved the lipid profile and restored insulin sensitivity. CAF-fed rats showed anxiety-like behaviors in the open field and light-dark box tasks but not in the contextual aversive conditioning. Omega-3 did not exert any effect on these behaviors. Regarding neuroinflammation, diet and supplementation acted in a region-specific manner. In the hippocampus, CAF reduced claudin-5 expression with no effect of n3, indicating a brain-blood barrier disruption following CAF. Furthermore, in the hippocampus, the glial fibrillary acidic protein (GFAP) and toll-like receptor 4 (TLR-4) were reduced in treated obese animals. However, n3 could not reverse the TLR-4 expression increase in the cerebral cortex.Discussion: Although n3 may protect against some neuroinflammatory manifestations in the hippocampus, it does not seem sufficient to reverse the increase in anxiolytic manifestations caused by CAF.


Assuntos
Ácidos Graxos Ômega-3 , Receptor 4 Toll-Like , Ratos , Masculino , Animais , Ratos Wistar , Doenças Neuroinflamatórias , Obesidade/etiologia , Obesidade/metabolismo , Dieta , Ácidos Graxos Ômega-3/farmacologia , Ansiedade/etiologia , Ansiedade/prevenção & controle , Suplementos Nutricionais
17.
Mar Drugs ; 22(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393051

RESUMO

The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.


Assuntos
Epilepsia , Ácidos Graxos Ômega-3 , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Suplementos Nutricionais , Encéfalo , Fosfolipídeos/uso terapêutico , Epilepsia/tratamento farmacológico
18.
Mar Drugs ; 22(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38921567

RESUMO

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDSs). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.


Assuntos
Doenças Cardiovasculares , Ácidos Graxos Ômega-3 , Nanopartículas , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Nanopartículas/química , Animais , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/química
19.
Mar Drugs ; 22(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38786598

RESUMO

This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.


Assuntos
Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácidos Graxos Ômega-3 , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/prevenção & controle , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Ferimentos e Lesões/cirurgia , Animais
20.
J Therm Biol ; 122: 103885, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38861860

RESUMO

The current study aimed to investigate the use of omega-6 (ω6) or omega-3 (ω3) in reducing heat-induced damage to the testicles. This is due to the known detrimental effects of heat and the potential protective properties of ω6 and ω3. In the study, 48 male rats were divided into eight groups, each containing 6 rats. Group I (control) received normal saline. Group 2 was exposed to high temperatures (43 °C for 20 min/day) and also received normal saline for 60 days. Groups 3-7 underwent identical HS conditions and received varying doses of ω6 or ω3 (0.5 mg/kg DHPG, 1 mg/kg DHPG, 5 mg/kg HT, 0.5 mg/kg DHPG + 5 mg/kg HT, and 1 mg/kg DHPG + 5 mg/kg HT), respectively. After 60 days, various tests were conducted on the testicular tissue, sperm quality, oxidative status, gene activity, and in vivo fertility indexes to evaluate the effects of the treatments. Treatment with ω6 and ω3 could reduce abnormal morphology and DNA damage while increasing total and progressive motility, characteristics motility, viability, and plasma membrane functional impairment compared with HS-exposed groups. Antioxidant status levels in testicular tissue were improved after administration of ω6 and ω3. Furthermore, after receiving ω6 and ω3, there were significantly lower expression levels of P53 and Caspase-3 and significantly higher expression levels of Bcl-2 compared to the HS-exposed group. Furthermore, the results showed that administration of ω6 and ω3 to rats exposed to HS could increase their in vivo fertility indexes compared to the group not exposed to HS. According to our data, all doses of ω6 and ω3 (particularly doses of ω6-1.25 and ω3-300) can improve the testicular damage, testicular antioxidant defense mechanism, regulate germ cell apoptosis, and increase in vivo fertility indexes.


Assuntos
Antioxidantes , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Fertilidade , Espermatogênese , Testículo , Animais , Masculino , Ácidos Graxos Ômega-3/farmacologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Espermatogênese/efeitos dos fármacos , Ratos , Ácidos Graxos Ômega-6/farmacologia , Fertilidade/efeitos dos fármacos , Antioxidantes/farmacologia , Resposta ao Choque Térmico/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Ratos Wistar
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