Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPARα

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1340-1346 ◽  
Author(s):  
Sanjeev Sethi ◽  
Ouliana Ziouzenkova ◽  
Heyu Ni ◽  
Denisa D. Wagner ◽  
Jorge Plutzky ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fish Oil ◽  
Inflammatory Diseases ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor

Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)–treated mice. This occurred via a PPARα-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARα-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARα-mediated anti-inflammatory effect of oxidized EPA.

scholarly journals Role of Omega-3 Polyunsaturated Fatty Acids in the Production of Prostaglandin E2and Nitric Oxide during Experimental Murine Paracoccidioidomycosis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
S. C. Sargi ◽  
M. M. O. Dalalio ◽  
A. G. Moraes ◽  
J. E. L. Visentainer ◽  
D. R. Morais ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Peritoneal Macrophages ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Potential Health ◽  
Macrophage Activity ◽  
Experimental Paracoccidioidomycosis

There has recently been increased interest in the potential health effects of omega-3 polyunsaturated fatty acids on the immune system. Paracoccidioidomycosis is the most important endemic mycosis in Latin America. Macrophages have a fundamental role and act as first line of organism defense. The purpose of this study was to analyze the effect of n-3 fatty acids on the production of PGE2and NO by mice infected with Pb18 and fed a diet enriched with LNA for 8 weeks. To study the effect of omega-3 fatty acids on macrophage activity during experimental paracoccidioidomycosis, mice were infected with Pb18 and fed a diet supplemented with LNA. PGE2in the serum of animals was analyzed and NO in the supernatants of macrophages cultured and challengedin vitrowith Pb18 was measured. Omega-3 fatty acids seemed to decrease the production of PGE2in vivoin the infected group fed an LNA-supplemented diet during the 4th and 8th weeks of the experiment. At the same time, we observed an increase in synthesis of NO by peritoneal macrophages in this group. Omega-3 fatty acids thus appear to have an immunomodulatory effect in paracoccidioidomycosis.

Cardioprotective role of omega-3 polyunsaturated fatty acids

2008 ◽  
Vol 149 (14) ◽  
pp. 627-637 ◽  
Author(s):  
Zsuzsa Varga
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Fish Oil ◽  
Linseed Oil ◽  
Density Lipoprotein ◽  
Receptor Protein ◽  
Peroxisome Proliferator ◽  
Nuclear Factor ◽  
Omega 3 Fatty Acids ◽  
Omega 3

Cardioprotective action of omega-3 polyunsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in fish and α-linolenic acid in plants was demonstrated in primary and secondary clinical trials. Fish oil therapy causes a marked decrease in serum triacylglycerol and very low density lipoprotein levels and increases moderately high density lipoprotein levels without any adverse effects. Omega-3 fatty acids decrease slightly, but significantly blood pressure, enhance endothelial function, they have anti-aggregator, anti-thrombotic and anti-inflammatory effects as well. These beneficial effects are in connection with modification of gene transcription levels of some key molecules such as nuclear factor-κB and sterol element binding receptor protein-1c, which regulate for example expression of adhesion molecules or several receptors involved in triglyceride synthesis (hepatocyte X receptor, hepatocyte nuclear factor 4α, farnesol X receptor, and peroxisome proliferator-activated receptors). On the basis of these observations, the supplementation of the diet with omega-3 fatty acids (fish, fish oil, linseed, and linseed oil or canola oil) is advisable in primary and secondary prevention.

scholarly journals Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing β-oxidation of fatty acid in mice

2019 ◽  
Vol 316 (4) ◽  
pp. G527-G538 ◽  
Author(s):  
Liu Yao ◽  
Boyang Cao ◽  
Qian Cheng ◽  
Wenbin Cai ◽  
Chenji Ye ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver

Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg·kg−1·day−1 for the animal model and 1 μM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-α (PPAR-α), as evidenced by elevated β-oxidation of fatty acids and the expression of PPAR-α target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-α activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-α. Of note, 11,12-EET ligand dependently activated PPAR-α. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-α was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.

scholarly journals Addition of marine omega-3 fatty acids to statins in familial hypercholesterolemia does not affect in vivo or in vitro endothelial function

2019 ◽  
Vol 13 (5) ◽  
pp. 762-770 ◽  
Author(s):  
Liv Nesse Hande ◽  
Hilde Thunhaug ◽  
Terje Enebakk ◽  
Judith Ludviksen ◽  
Kristin Pettersen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endothelial Function ◽  
Familial Hypercholesterolemia ◽  
Omega 3 Fatty Acids ◽  
Omega 3

scholarly journals Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism

2020 ◽  
Vol 8 (1) ◽  
pp. e000871 ◽  
Author(s):  
Charlotte J Green ◽  
Camilla Pramfalk ◽  
Catriona A Charlton ◽  
Pippa J Gunn ◽  
Thomas Cornfield ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasma Glucose ◽  
De Novo ◽  
In Vitro Studies ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Omega 3 Fatty Acids ◽  
Omega 3

ObjectiveIncreased hepatic de novo lipogenesis (DNL) is suggested to be an underlying cause in the development of nonalcoholic fatty liver disease and/or insulin resistance. It is suggested that omega-3 fatty acids (FA) lower hepatic DNL. We investigated the effects of omega-3 FA supplementation on hepatic DNL and FA oxidation using a combination of human in vivo and in vitro studies.Research design and methodsThirty-eight healthy men were randomized to take either an omega-3 supplement (4 g/day eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) as ethyl esters) or placebo (4 g/day olive oil) and fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on intrahepatocellular triacylglycerol (IHTAG) content, hepatic DNL and FA oxidation were investigated using metabolic substrates labeled with stable-isotope tracers. In vitro studies, using a human liver cell-line was undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs.ResultsFasting plasma TAG concentrations significantly decreased in the omega-3 group and remained unchanged in the placebo group. Eight weeks of omega-3 supplementation significantly decreased IHTAG, fasting and postprandial hepatic DNL while significantly increasing dietary FA oxidation and fasting and postprandial plasma glucose concentrations. In vitro studies supported the in vivo findings of omega-3 FAs (EPA+DHA) decreasing intracellular TAG through a shift in cellular metabolism away from FA esterification toward oxidation.ConclusionsOmega-3 supplementation had a potent effect on decreasing hepatic DNL and increasing FA oxidation and plasma glucose concentrations. Attenuation of hepatic DNL may be considered advantageous; however, consideration is required as to what the potential excess of nonlipid substrates (eg, glucose) will have on intrahepatic and extrahepatic metabolic pathways.Trial registration numberNCT01936779.

Abstract 2454: Omega-3 fatty acids DHA and EPA decrease oncogenic PGE2 in medulloblastoma in vitro and in vivo

2016 ◽  
Author(s):  
Linda Ljungblad ◽  
Filip Bergqvist ◽  
Teodora Andonova ◽  
Per-Johan Jakobsson ◽  
John Inge Johnsen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Omega 3 Fatty Acids ◽  
Omega 3

scholarly journals Omega-3 Fatty Acids-Enriched Fish Oil Activates AMPK/PGC-1α Signaling and Prevents Obesity-Related Skeletal Muscle Wasting

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 380 ◽  
Author(s):  
Shing-Hwa Liu ◽  
Chen-Yuan Chiu ◽  
Lou-Pin Wang ◽  
Meng-Tsan Chiang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fish Oil ◽  
Muscle Wasting ◽  
Peroxisome Proliferator ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Sprague Dawley ◽  
Final Body Weight ◽  
Skeletal Muscle Wasting

Obesity is known to cause skeletal muscle wasting. This study investigated the effect and the possible mechanism of fish oil on skeletal muscle wasting in an obese rat model. High-fat (HF) diets were applied to induce the defects of lipid metabolism in male Sprague-Dawley rats with or without substitution of omega-3 fatty acids-enriched fish oil (FO, 5%) for eight weeks. Diets supplemented with 5% FO showed a significant decrease in the final body weight compared to HF diet-fed rats. The decreased soleus muscle weights in HF diet-fed rats could be improved by FO substitution. The decreased myosin heavy chain (a muscle thick filament protein) and increased FOXO3A and Atrogin-1 (muscle atrophy-related proteins) protein expressions in soleus muscles of HF diet-fed rats could also be reversed by FO substitution. FO substitution could also significantly activate adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, peroxisome-proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α), and PPARγ protein expression and lipoprotein lipase (LPL) mRNA expression in soleus muscles of HF diet-fed rats. These results suggest that substitution of FO exerts a beneficial improvement in the imbalance of lipid and muscle metabolisms in obesity. AMPK/PGC-1α signaling may play an important role in FO-prevented obesity-induced muscle wasting.

Omega-3-fatty acids improve in vivo and in vitro platelet function

1994 ◽  
Vol 109 (1-2) ◽  
pp. 322
Author(s):  
C. Pirich ◽  
A. Gaszo ◽  
D. Horrobin ◽  
S. Granegger ◽  
H. Sinzinger
Keyword(s):  
Fatty Acids ◽  
Platelet Function ◽  
Omega 3 Fatty Acids ◽  
Omega 3

Fish oil plus wheat germ oil have no prominent effect on homocysteine levels and nutritional indices in hemodialysis patients

2019 ◽  
pp. 1-7
Author(s):  
Hadeer Zakaria ◽  
Tarek M. Mostafa ◽  
Gamal A. El-Azab ◽  
Nagy AH Sayed-Ahmed
Keyword(s):  
Fatty Acids ◽  
Vitamin E ◽  
Fish Oil ◽  
Wheat Germ ◽  
Hemodialysis Patients ◽  
Nutritional Indices ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Wheat Germ Oil ◽  
Serum Homocysteine

Abstract. Background: Elevated homocysteine levels and malnutrition are frequently detected in hemodialysis patients and are believed to exacerbate cardiovascular comorbidities. Omega-3 fatty acids have been postulated to lower homocysteine levels by up-regulating metabolic enzymes and improving substrate availability for homocysteine degradation. Additionally, it has been suggested that prevention of folate depletion by vitamin E consumption decreases homocysteine levels. However, data on the effect of omega-3 fatty acids and/or vitamin E on homocysteine levels and nutritional status have been inconclusive. Therefore, this study was planned to examine the effect of combined supplementation of fish oil, as a source of omega-3 fatty acids, with wheat germ oil, as a source of vitamin E, on homocysteine and nutritional indices in hemodialysis patients. Methods: This study was a randomized, double-blind, placebo-controlled trial. Forty-six hemodialysis patients were randomly assigned to two equally-sized groups; a supplemented group who received 3000 mg/day of fish oil [1053 mg omega-3 fatty acids] plus 300 mg/day of wheat germ oil [0.765 mg vitamin E], and a matched placebo group who received placebo capsules for 4 months. Serum homocysteine and different nutritional indices were measured before and after the intervention. Results: Twenty patients in each group completed the study. At the end of the study, there were no significant changes in homocysteine levels and in the nutritional indices neither in the supplemented nor in the placebo-control groups (p > 0.05). Conclusions: Fish oil and wheat germ oil combination did not produce significant effects on serum homocysteine levels and nutritional indices of hemodialysis patients.

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