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1.
Nutrients ; 13(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530352

RESUMO

The clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients' nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan-Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06-0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Insuficiência Cardíaca/sangue , Volume Sistólico , Ácido 8,11,14-Eicosatrienoico/sangue , Idoso , Idoso de 80 Anos ou mais , Ácido Araquidônico/sangue , Causas de Morte , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Masculino , Estado Nutricional , Plasma , Prognóstico , Estudos Retrospectivos , Fatores de Risco
2.
Nutrients ; 13(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530576

RESUMO

BACKGROUND: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. METHODS: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40-80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 ± 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings. RESULTS: A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07; p = 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC. CONCLUSIONS: We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.


Assuntos
Biomarcadores/sangue , Ácidos Graxos Ômega-3/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/análogos & derivados , Eritrócitos , Óleos de Peixe , Peixes , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Mol Aspects Med ; 77: 100943, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33551236

RESUMO

The health of the individual and the population in general is the result of interaction between genetics and various environmental factors, of which diet/nutrition is the most important. The focus of this paper is on the association of high n-6 PUFA or low n-3 PUFA due to genetic variation and/or dietary intake, with changes in specialized pro-resolving mediators (SPMs), cytokine storm, inflammation-resolution and Covid-19. Human beings evolved on a diet that was balanced in the n-6 and n-3 essential fatty acids with a ratio of n-6/n-3 of 1-2/1 whereas today this ratio is 16/1. Such a high ratio due to high amounts of n-6 fatty acids leads to a prothrombotic and proinflammatory state and is associated with obesity, diabetes, cardiovascular disease, and some forms of cancer. In addition to the high intake of n-6 fatty acids that increases inflammation there is genetic variation in the biosynthesis of n-6 linoleic acid (LA) to arachidonic acid (ARA) and of linolenic (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Present day humans have two common FADS haplotypes that differ dramatically in their ability to generate long-chain fatty acids. The more efficient, evolutionary derived haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and could have provided an advantage in environments with limited access to dietary long-chain fatty acids ARA, EPA and DHA. In the modern world this haplotype has been associated with lifestyle-related diseases, such as cardiovascular disease, obesity, diabetes, all of which are characterized by increased levels of inflammation. African Americans and Latino populations have increased susceptibility and higher death rates from SARS-CoV-2 than whites. These populations are characterized by increased numbers of persons (about 80%) that are fast metabolizers, leading to increased production of ARA, as well as poor intake of fruits and vegetables. The combinations of fast metabolism and high n-6 intake increases their inflammatory status and possibly susceptibility of SARS-CoV-2. In vitro and human studies indicate that the specialized pro-resolving mediators (SPM) produced from the n-3, EPA and DHA influence the resolution of inflammation, allowing the tissues to return to function and homeostasis. The SPMs each counter-regulate cytokine storms, as well as proinflammatory lipid mediators via NFκB and inflammasome down regulation and reduce the proinflammatory eicosanoids produced from ARA. The nutritional availability of dietary n-3 fatty acids from marine oils enriched with SPM intermediate precursors, along with increasing local biosynthesis of SPMs to functional concentrations may be an approach of value during SARS-CoV2 infections, as well as in prevention, and shortening their recovery from infections. It is evident that populations differ in their genetic variants and their frequencies and their interactions with the food they eat. Gene-nutrient interactions is a very important area of study that provides specific dietary advice for individuals and subgroups within a population in the form of Precision Nutrition. Nutritional science needs to focus on Precision Nutrition, genetic variants in the population and a food supply composed of Nutrients that have been part of our diet throughout evolution, which is the diet that our genes are programmed to respond.


Assuntos
/dietoterapia , /genética , /metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Eicosanoides/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Essenciais/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Inflamação/dietoterapia , Inflamação/genética , Inflamação/metabolismo , Ácido Linoleico/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , /patogenicidade
5.
Am Heart J ; 235: 54-64, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33516752

RESUMO

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.


Assuntos
Aterosclerose/complicações , Doenças Cardiovasculares/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Inibidores da Agregação de Plaquetas/uso terapêutico , Idoso , Doenças Cardiovasculares/complicações , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/complicações , Infecções Respiratórias/virologia
6.
Chemosphere ; 262: 128249, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182142

RESUMO

Saltwater fish is rich in health-promoting polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Excessive fish intake may also cause health hazards due to methylmercury (MeHg). A novel dose estimation method was proposed in this study to improve the quality of food matching by considering the usage ratio of cooking and processing methods in sampling design. In total, 39 table-ready samples were specified according to 2-3 common cooking methods, and MeHg and total mercury (THg) were analyzed. The results showed that mercury was detected in 20 samples (LOD = 0.01 µg/g). High MeHg samples included fried-Spanish mackerel (1.23 µg/g), non-cooked shredded swordfish (0.325 µg/g), pan-fried Spanish mackerel (0.248 µg/g), and non-cooked shredded salmon (0.208 µg/g). Consumption data (n = 166,911) were obtained from 24-h recalls in the 2005-2008 Nutrition and Health Surveys in Taiwan (NAHSIT). The average whole-group estimated daily intake (EDI_WG) was 0.018 (7.9% tolerable daily intake, TDI) for women of child-bearing age and 0.031 µg/day per kg body weight (13.6% TDI) for children. However, 95th percentile values (P95) of 90.4% TDI and 185% TDI were estimated for the two consumer-only populations, which have raised public health concerns. The ratio of % TDI to % daily reference intake (% DRI) was used as a risk-benefit (R/B) indicator. The top 4 R/B foods were: tuna sashimi (0.089 and 0.14), non-cooked shredded swordfish (0.033 and 0.052), fried-Spanish mackerel (0.027 and 0.043) and deep-fried fish balls (0.022 and 0.035) in the two perspective populations.


Assuntos
Exposição Dietética/análise , Ácidos Graxos Insaturados/análise , Peixes/metabolismo , Compostos de Metilmercúrio/análise , Alimentos Marinhos/análise , Adulto , Animais , Criança , Culinária , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/análise , Feminino , Humanos , Pessoa de Meia-Idade , Saúde Pública , Medição de Risco , Taiwan
7.
Am J Case Rep ; 21: e928422, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33311431

RESUMO

BACKGROUND Icosapent ethyl, a form of eicosapentaenoic acid with anti-inflammatory activity, has been approved as an adjunctive treatment with statins in patients with hypertriglyceridemia. Icosapent ethyl is currently undergoing clinical trials to determine its anti-inflammatory effects in patients with coronavirus disease 2019 (COVID-19). This report describes 3 intensive care unit (ICU) patients with moderate to severe COVID-19 pneumonia treated with icosapent ethyl as part of their supportive care who had favorable outcomes. CASE REPORT Case 1 was a 75-year-old man with a past medical history of hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and benign prostatic hyperplasia. Case 2 was a 23-year old man with a past medical history of type 2 diabetes mellitus and obesity. Case 3 was a 24-year old man with a history of autism. All cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed from a nasopharyngeal swab using the Becton Dickinson nasopharyngeal reverse-transcription polymerase chain reaction. All patients in these cases were treated with a course of 2 g of icosapent ethyl twice a day by nasogastric tube. CONCLUSIONS This report of 3 cases describes the use of icosapent ethyl as a component of supportive treatments in ICU patients with moderate to severe COVID-19 pneumonia. However, as of yet there are no evidence-based treatments for SARS-CoV-2 infection from controlled clinical trials. The outcomes of ongoing clinical trials are awaited to determine whether icosapent ethyl has anti-inflammatory effects in patients with SARS-CoV-2 infection and which patients might benefit from the use of this adjunctive treatment.


Assuntos
/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Idoso , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Masculino , Adulto Jovem
8.
Curr Atheroscler Rep ; 22(12): 72, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009957

RESUMO

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the 2020 European Society of Cardiology (ESC) Congress-The Digital Experience. RECENT FINDINGS: The studies reviewed include clinical trials on novel RNA interference-based lipid-lowering therapies AKCEA-APOCIII-LRx and vupanorsen (AKCEA-ANGPTL3-LRx); the EVAPORATE trial assessing the effects of icosapent ethyl on coronary plaque volume progression; the LoDoCo2 trial evaluating the efficacy of low-dose colchicine in cardiovascular disease risk reduction among patients with chronic coronary artery disease; as well as the EMPEROR-Reduced trial evaluating cardiovascular and renal outcomes with empagliflozin in patients with heart failure and reduced ejection fraction. In addition, we review the BPLTTC analysis on blood pressure treatment across blood pressure levels and CVD status and discuss findings from the BRACE CORONA study that examined continuing versus suspending angiotensin-converting enzyme inhibitor or angiotensin receptor blockers in patients on these antihypertensive medications who were hospitalized with COVID-19 infection. The studies presented at the 2020 digital ESC Congress highlight the continuing advancements in the field of CVD prevention.


Assuntos
Betacoronavirus/fisiologia , Cardiologia , Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares , Infecções por Coronavirus , Reguladores do Metabolismo de Lipídeos/farmacologia , Pandemias , Pneumonia Viral , Compostos Benzidrílicos/farmacologia , Cardiologia/métodos , Cardiologia/tendências , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Congressos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Europa (Continente) , Glucosídeos/farmacologia , Humanos , Oligonucleotídeos/farmacologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Sociedades Médicas , Telecomunicações
9.
Maturitas ; 141: 39-45, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33036701

RESUMO

OBJECTIVES: To investigate the effect of omega-3 (ω-3) polyunsaturated fatty acid supplementation and a multidomain intervention (MI) (physical activity counselling, cognitive training and nutritional advice) among community-dwelling older adults on levels of intrinsic capacity (IC), a construct recently proposed by the World Health Organization. STUDY DESIGN: Secondary analysis from the factorial-design 3-year Multidomain Alzheimer Preventive Trial (MAPT) with 1445 subjects (64.2 % female, mean age 75.3 years, SD = 4.4) randomized to one group of MI plus ω-3 (800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid/day); MI plus placebo; ω-3 supplementation alone; or placebo alone. Data collection was held between 2008 and 2014. MAIN OUTCOME MEASURES: IC domains were examined with the Geriatric Depression Scale (psychological); Short Physical Performance Battery (mobility); Z-score combining four tests (cognitive function); and handgrip strength (vitality). All domains were combined into a composite IC Z-score. RESULTS: After 3 years, IC Z-score decreased among all groups when time was considered continuous (MI plus ω-3: -0.16, 95 %CI: -0.22 to -0.10; MI alone: -0.13, 95 %CI: -0.19 to -0.07; ω-3 alone: -0.19, 95 %CI: -0.25 to -0.10; placebo: -0.20, 95 %CI: -0.26 to -0.14; all p < 0.0001). There were no significant differences between groups. In a sensitivity analysis with categorical time, significant within-group declines were first identified at 24 months for all groups. CONCLUSIONS: This trial designed to improve cognitive function was unable to find effects of the intervention on the composite IC Z-score. Further investigations are needed, especially trials providing stronger interventions (such as exercise training and a controlled diet) and also embracing the sensorial domain of IC.


Assuntos
Doença de Alzheimer/prevenção & controle , Cognição/efeitos dos fármacos , Ácidos Graxos Ômega-3/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico/análogos & derivados , Exercício Físico , Ácidos Graxos Ômega-3/farmacologia , Feminino , Avaliação Geriátrica , Força da Mão , Estilo de Vida Saudável , Humanos , Vida Independente , Estilo de Vida , Estudos Longitudinais , Masculino , Amplitude de Movimento Articular/efeitos dos fármacos
10.
Nat Commun ; 11(1): 4865, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978396

RESUMO

The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.


Assuntos
Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Regulação da Expressão Gênica , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Fenômenos Bioquímicos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Ácido Linoleico/metabolismo , Longevidade , Redes e Vias Metabólicas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
11.
Am J Cardiol ; 134: 62-68, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933754

RESUMO

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c <10%, blood pressure <200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Definição da Elegibilidade , Reguladores do Metabolismo de Lipídeos/uso terapêutico , Revascularização Miocárdica/estatística & dados numéricos , Idoso , Angina Instável/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Inquéritos Nutricionais , Prevenção Primária , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle
13.
Arch Biochem Biophys ; 691: 108486, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32710880

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Because hepatic steatosis is an early pathogenesis of NAFLD, the discovery of food components that could ameliorate hepatic steatosis is of interest. Susabinori (Pyropia yezoensis) is recognized as one of the most delicious edible brown algae, and we prepared lipid component of susabinori (SNL), which is rich in eicosapentaenoic acid (EPA)-containing polar lipids. In this study, we tested whether feeding SNL to db/db mice protects them from developing obesity-induced hepatic steatosis. After four weeks of feeding, hepatomegaly, hepatic steatosis, and hepatic injury were markedly alleviated in SNL-fed db/db mice. These effects were partly attributable to the suppression of activities and mRNA expressions of lipogenic enzymes and enhanced levels of adiponectin due to the SNL diet. Additionally, mRNA expression of monocyte chemoattractant protein-1, an inflammatory chemokine, was markedly suppressed, and the mRNA levels of PPARδ, the anti-inflammatory transcription factor, were strongly enhanced in the livers of db/db mice by the SNL diet. We speculate that the development and progression of obesity-induced hepatic steatosis was prevented by the suppression of chronic inflammation due to the combination of bioactivities of EPA, phospholipids, and glycolipids in the SNL diet.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Extratos Vegetais/farmacologia , Alga Marinha/química , Animais , Quimiocina CCL2/metabolismo , Glicolipídeos/farmacologia , Hepatomegalia/metabolismo , Hepatomegalia/prevenção & controle , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR delta/metabolismo , Fosfolipídeos/farmacologia , RNA Mensageiro/metabolismo , Rodófitas/química
14.
Am J Pathol ; 190(9): 1823-1832, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32561135

RESUMO

Leukotriene B4 (LTB4) is a major proinflammatory mediator important in host defense, whereas resolvins (Rvs) are produced during the resolution phase of inflammation. The authors determined the actions of both RvE1 and RvD1 on LTB4-induced responses of goblet cells cultured from rat conjunctiva. The responses measured were an increase in the intracellular [Ca2+] ([Ca2+]i) and high-molecular-weight glycoprotein secretion. Treatment with RvE1 or RvD1 for 30 minutes significantly blocked the LTB4-induced [Ca2+]i increase. The actions of RvE1 on LTB4-induced [Ca2+]i increase were reversed by siRNA for the RvE1 receptor, and the actions of RvD1 were reversed by an RvD1 receptor inhibitor. The RvE1 and RvD1 block of LTB4-stimulated increase in [Ca2+]i was also reversed by an inhibitory peptide to ß-adrenergic receptor kinase. LTB4 and block of the LTB4-stimulated increase in [Ca2+]i by RvE1 and RvD1 were partially mediated by the depletion of intracellular Ca2+ stores. RvE1, but not RvD1, counterregulated the LTB4-induced high-molecular-weight glycoprotein secretion. Thus, both RvE1 and RvD1 receptors directly inhibit LTB4 by phosphorylating the LTB4 receptor using ß adrenergic receptor kinase. RvE1 receptor counterregulates the LTB4-induced increase in [Ca2+]i and secretion, whereas RvD1 receptor only counterregulates LTB4-induced [Ca2+]i increase.


Assuntos
Cálcio/metabolismo , Túnica Conjuntiva/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Células Caliciformes/metabolismo , Leucotrieno B4/metabolismo , Mucinas/metabolismo , Animais , Ácido Eicosapentaenoico/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
15.
J Food Sci ; 85(7): 1983-1987, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32572984

RESUMO

Because omega-3 fatty acids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites are known to possess anti-inflammatory and health-promoting functions in human and experimental animals, their intake is assumed to be beneficial for maintaining our health. We previously identified a cytochrome P450-metabolite of EPA, 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE), as a novel bioactive lipid, which inhibits vascular hyperpermeability in inflammation. Because blue back fishes including sardine, mackerel, and horse mackerel are reported to contain high concentrations of omega-3 fatty acids, we investigated which tissue of blue back fish is suitable as a source of 5,6-DiHETE. We measured the concentration of 5,6-DiHETE as well as major fatty acids in muscle, bone, heart, liver, and intestine of blue back fishes. Arachidonic acid was detected richer in intestines than other tissues of blue back fishes. The concentrations were between 4.45 and 5.62 µg/g tissue weight. EPA and DHA are also detected richer in intestines of blue back fishes. The concentrations were between 75.95 and 358.04 µg/g, and 203.09 and 464.88 µg/g, respectively. Especially, mackerel intestine contained the highest levels of both EPA and DHA. 5,6-DiHETE was present in greater amount in livers and intestines of blue back fishes. The livers contained 118.98 to 476.11 ng/g, whereas intestines contained 156.14 to 970.22 ng/g of 5,6-DiHETE. Of interest, sardine intestine contained much higher level of 5,6-DiHETE than the other fish tissues. These results suggest that visceral organs of blue back fishes, remarkably sardine intestine, can be a good source of 5,6-DiHETE. PRACTICAL APPLICATION: A novel anti-inflammatory lipid, 5,6-DiHETE, was detected in each tissues of blue back fishes. Especially their intestines contain the highest concentration of this lipid.


Assuntos
Anti-Inflamatórios/química , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Peixes/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/química , Alimentos Marinhos/análise
16.
PLoS One ; 15(6): e0235217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574225

RESUMO

In sheep, polyunsaturated fatty acid (PUFA) supplementations in late gestation increases the growth of offspring; however, there is a lack of evidence on the effect of PUFA supplementation during early gestation. Thus, the objective of this study was to evaluate the effect of dietary supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in early gestation pregnant ewes on fatty acid concentration of fetal liver (FL) and fetal central nervous system (FCNS), and relative abundance of the mRNA for genes associated with transport and metabolism of fatty acids in FL and placenta. A total of 12 ewes, block for stage of gestation were fed a diet containing 1.6% (dry matter basis) monounsaturated fatty acids (MUFA) or EPA+DHA during the first 45 days of gestation. A cesarean section was conducted on day 45 of gestation to collect placenta (caruncle and cotyledon), FL, and FCNS. Relative abundance of mRNA in FL and FCNS and fatty acid concentration were analyzed using a 2x2 factorial arrangement of treatments considering fatty acid supplementation and tissue as the main factors. Concentrations of C18:1 isomers increase (P < 0.05) in FL and FCNS with MUFA supplementation; the FL and FCNS had a greater concentration of C20:3(n-6), C20:3(n-3), C22:1, C22:5 and C22:6 (P < 0.05) with EPA+DHA supplementation. In FL, the relative abundance of LPL mRNA was greater (P = 0.02) as a result of MUFA supplementation. In placenta, there was a FA x tissue interaction for relative abundance of DNMT3b and FFAR-4 mRNA (P < 0.05). Fetus from MUFA-supplemented dams had a greater relative abundance of FABP-4 mRNA (P < 0.05). Results indicate supplementation with EPA+DHA during early gestation increases the total EPA and DHA in FL. For the placenta, EPA+DHA supplementation led to an increase in the relative abundance of lipid mRNA for transport genes.


Assuntos
Sistema Nervoso Central/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos/análise , Feto/efeitos dos fármacos , Placenta/efeitos dos fármacos , RNA Mensageiro/metabolismo , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Suplementos Nutricionais , Ácido Eicosapentaenoico/farmacologia , Proteínas de Ligação a Ácido Graxo/genética , Ácidos Graxos/química , Feminino , Feto/metabolismo , Idade Gestacional , Lipase Lipoproteica/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Placenta/metabolismo , Gravidez , Ovinos
18.
Expert Rev Cardiovasc Ther ; 18(4): 175-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228246

RESUMO

INTRODUCTION: Icosapent ethyl (IPE) is a highly purified (>96%) form of eicosapentanoic acid, a marine-derived omega-3 fatty acid known to reduce serum triglyceride (TG) levels. In the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), the addition of 4 g IPE daily resulted in a 25% reduction in cardiovascular events beyond statins and other standard of care therapies. IPE is now the only therapy currently approved by the Food and Drug Administration to treat patients with elevated TGs (150-499 mg/dL) with cardiovascular disease (CVD) or Type 2 diabetes mellitus and two or more CVD risk factors.Areas covered: IPE is a highly purified form of eicosapentanoic acid for patients with elevated TGs as monotherapy or combined with statins and/or other lipid lowering therapies.The REDUCE-IT Study demonstrated a 25% reduction in the primary outcome measure and 30% reduction in total CVD events in high-risk patients with elevated TGs (135-499 mg/dL) assigned to IPE (4 g daily).Side effects included a statistically significant increased risk of atrial fibrillation and bleeding, although the risk of stroke was reduced and there were no cases of fatal bleeding.The FDA recently approved IPE for treatment of patients with TG levels of 150-499 mg/dL and preexisting CVD or Type 2 diabetes mellitus with two or more risk factors.Expert opinion:IPE has proven to be superior to other forms of omega 3 fatty acid in reducing CVD risk in patients with elevated TG. This could be attributed to multiple factors including the use of highly purified eicosapentaenoic acid ethyl esters without docosahexaenoic acid (DHA), thus preventing the increase in low-density lipoprotein cholesterol associated with DHA especially at high TG levels, reduction in atherogenic TG-rich particles, antioxidant and anti-inflammatory properties, improvement in endothelial function, and stabilization of atherosclerotic plaque.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/sangue , Ácido Eicosapentaenoico/análogos & derivados , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aterosclerose/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácido Eicosapentaenoico/administração & dosagem , Humanos , Hipertrigliceridemia/tratamento farmacológico , Fatores de Risco , Triglicerídeos/sangue
19.
Lett Appl Microbiol ; 71(2): 164-170, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32306412

RESUMO

Mortierella alpina has gained remarkable interest due to its high capacity for arachidonic acid (AA) production and potential for eicosapentaenoic acid (EPA) production recently. However, the development of genetically modified strains is limited by lacking inducible promoters, which can express genes conditionally. Here the inducible promoter of cellobiohydrolase (Pcbh1) was utilized in M. alpina and the gene oPpFADS17 encoding ω-3 fatty acid desaturase was selected as the reporter gene. Under conditions with inducer, expression of this gene enables M. alpina to produce EPA at room temperature, while no EPA was detected without inducer. We then optimized the induction conditions. The results demonstrated that the optimal induction condition was broth medium with 1% avicel as the inducer and 5% glucose as extra carbon source and the transcription level of the reporter gene was increasing with the extension of induction time. Successful application of Pcbh1 in M. alpina would significantly contribute to the steerable system to construct engineered strains for industrial production of microbial oils. SIGNIFICANCE AND IMPACT OF THE STUDY: Mortierella alpina is a commercial strain for production of polyunsaturated fatty acids. Genetic engineering strategies based on M. alpina require the development of inducible promoters to regulate gene expression conditionally at specific times. However, available inducible promoters for M. alpina were limited. In this study, we explore the feasibility of inducible cbh1 promoter in M. alpina and determined the optimal induction condition, which accelerates the genetic manipulation of M. alpina. Besides, high transcriptional levels of the reporter gene under the control of Pcbh1 showed that Pcbh1 is a strong inducible promoter for M. alpina.


Assuntos
Ácidos Graxos Dessaturases/genética , Engenharia Genética/métodos , Mortierella/genética , Mortierella/metabolismo , Regiões Promotoras Genéticas/genética , Ácido Araquidônico/biossíntese , Celulose 1,4-beta-Celobiosidase/genética , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/biossíntese , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica , Genes Reporter/genética , Mortierella/crescimento & desenvolvimento
20.
Proc Natl Acad Sci U S A ; 117(17): 9477-9482, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32300016

RESUMO

Resolution of intestinal inflammation and wound repair are active processes that mediate epithelial healing at mucosal surfaces. Lipid molecules referred to as specialized proresolving mediators (SPMs) play an important role in the restorative response. Resolvin E1 (RvE1), a SPM derived from omega-3 fatty acids, has been reported to dampen intestinal inflammation by promoting anti-inflammatory responses including increased neutrophil spherocytosis and macrophage production of IL-10. Despite these observations, a role for RvE1 in regulating intestinal epithelial cell migration and proliferation during mucosal wound repair has not been explored. Using an endoscopic biopsy-based wound healing model, we report that RvE1 is locally produced in response to intestinal mucosal injury. Exposure of intestinal epithelial cells to RvE1 promoted wound repair by increasing cellular proliferation and migration through activation of signaling pathways including CREB, mTOR, and Src-FAK. Additionally, RvE1-triggered activation of the small GTPase Rac1 led to increased intracellular reactive oxygen species (ROS) production, cell-matrix adhesion, and cellular protrusions at the leading edge of migrating cells. Furthermore, in situ administration of RvE1-encapsulated synthetic targeted polymeric nanoparticles into intestinal wounds promoted mucosal repair. Together, these findings demonstrate that RvE1 functions as a prorepair lipid mediator by increasing intestinal epithelial cell migration and proliferation, and highlight potential therapeutic applications for this SPM to promote mucosal healing in the intestine.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Mucosa Intestinal/metabolismo , Cicatrização/fisiologia , Animais , Adesão Celular , Linhagem Celular , Colo , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacologia , Humanos , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Neuropeptídeos , Organoides , Espécies Reativas de Oxigênio , Proteínas rac1 de Ligação ao GTP
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