Omega-3 Free Fatty Acids Research Articles

Gene therapy for fat-1 prevents obesity-induced metabolic dysfunction, cellular senescence, and osteoarthritis

Obesity is one of the primary risk factors for osteoarthritis (OA), acting through cross talk among altered biomechanics, metabolism, adipokines, and dietary free fatty acid (FA) composition. Obesity and aging have been linked to cellular senescence in various tissues, resulting in increased local and systemic inflammation and immune dysfunction. We hypothesized that obesity and joint injury lead to cellular senescence that is typically associated with increased OA severity or with aging and that the ratio of omega-6 (ω-6) to omega-3 (ω-3) FAs regulates these pathologic effects. Mice were placed on an ω-6-rich high-fat diet or a lean control diet and underwent destabilization of the medial meniscus to induce OA. Obesity and joint injury significantly increased cellular senescence in subcutaneous and visceral fat as well as joint tissues such as synovium and cartilage. Using adeno-associated virus (AAV) gene therapy for fat-1, a fatty acid desaturase that converts ω-6 to ω-3 FAs, decreasing the serum ω-6:ω-3 FA ratio had a strong senomorphic and therapeutic effect, mitigating metabolic dysfunction, cellular senescence, and joint degeneration. In vitro coculture of bone marrow-derived macrophages and chondrocytes from control and AAV8-fat1-treated mice were used to examine the roles of various FA mediators in regulating chondrocyte senescence. Our results suggest that obesity and joint injury result in a premature "aging" of the joint as measured by senescence markers, and these changes can be ameliorated by altering FA composition using fat-1 gene therapy. These findings support the potential for fat-1 gene therapy to treat obesity- and/or injury-induced OA clinically.

The content of selected omega-3 free fatty acids in breast milk samples and their interactions with macronutrients as well as personal characteristics of mothers

Human milk contains many nutritional and non-nutritional components, including free fatty acids (FFAs) such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These acids were determined in 67 breast milk samples collected from Polish women. The average content of FFAs was 0.3 ± 0.2 mg g−1 of fat for EPA, 1.4 ± 0.6 mg g−1 of fat for ALA, and 0.4 ± 0.3 mg g−1 of fat for DHA. In each milk sample energy, fat, carbohydrate, crude and true protein, and total solids were also determined. The correlations between the content of FFAs and/or macronutrients and other parameters characteristic of nursing milk donors were found using statistical analysis. Among the most important connections with EPA, DHA, ALA contents are an effect of dietary and lactation supplements, eating habits, or breastfeeding complications.

Unsaturated bond recognition leads to biased signal in a fatty acid receptor.

Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and Gi or Giq trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.

Oral Mucositis in Cancer and Potential Use of Omega-3 Free Fatty Acids in Its Management: A Review.

Oral mucositis (OM) is a painful condition caused by chemotherapeutic or radiotherapeutic cancer treatments, occurring in patients with different tumour characteristics and locations. OM greatly impacts a patient’s quality of life and cancer recovery. Current OM management strategies are not providing sufficient prevention and treatment; new approaches to injury management are needed. Studies on the benefit of omega-3 free fatty acids (FFA) in human health have increased significantly in recent years. FFA properties have been studied extensively, including their potential therapeutic use in inflammatory conditions. However, omega-3 FFA’s use as a supplementary treatment for OM has not been clinically tested. Preliminary evidence suggests that utilising FFA to manage OM could be a useful strategy for lesion management, assisting with healthy oral mucosa recovery. This review will describe the incidence, risk factors, biology of OM and the current treatment strategies, leading to a discussion of the utility of omega-3 FFA as a novel therapeutic agent for OM.

Targeting dyslipidemia with antioxidative vitamins C, D, and E; a systematic review of meta-analysis studies: Dyslipidemia and antioxidative vitamins.

There is controversial evidence for the beneficial effects of antioxidative vitamins (vits) on dyslipidemia. In this regard, we aimed to systematically review all meta-analyses of trials on this topic. We comprehensively searched PubMed, Web of Science, Scopus, and Cochrane Library databases until January 2021 to explore the published English meta-analyses of trials conducted to assess the effects of single or combined vits C, D and E consumption on lipid profile. The meta-analyses of observational, in vivo/in vitro, or case-report studies were excluded. Search results were reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart. Overall, 25 meta-analyses including 32,177 individuals with different underlying disorders met our inclusion criteria. Numerous studies had assessed supplementation with Vit-D or its combination with other agents on lipid profile. Consumption of 400IU/day (d) to 50,000IU/week (w) Vit-D for at least eight weeks improved the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in type 2 diabetes mellitus or polycystic ovary syndrome (PCOS) patients. This treatment reduced the levels of TC and TG in patients with chronic kidney disease. A significant increase in high-density lipoprotein cholesterol (HDL-C) levels was only observed in coronary artery disease patients. Sole intake of 500-2000mg/d Vit-C for at least 3weeks improved LDL-C and TG values in hypercholesterolemic patients. Nevertheless, sole intake of Vit-E had controversial effects on lipid profile. The combination of 400-1800IU/d omega-3 free fatty acid (FFA) and 400IU/d Vit-E significantly reduced the levels of LDL-C and TG in overweight individuals, without any significant effect on other components. A significant improvement of TG values was observed after consumption of 1000-2000mg/d omega-3 FFA plus 400IU/d Vit-E along with 50,000IU/each 2w Vit-D for at least 6weeks in diabetic patients. The beneficial effects of antioxidative vitamins (C, D, E) or their combination with other agents on lipid profile varied based on their dosage, intake duration, and the health status of the individuals. The online version contains supplementary material available at 10.1007/s40200-021-00919-8.

Evaluating the Impact of Omega-3 Free Fatty Acid Supplementation on Postoperative Complications in Obese Postmenopausal Women With Estrogen Receptor Positive Breast Cancer.

Evaluating the Impact of Omega-3 Free Fatty Acid Supplementation on Postoperative Complications in Obese Postmenopausal Women With Estrogen Receptor Positive Breast Cancer.

What is new in lipid-lowering therapies in diabetes?

Diabetes can lead to a myriad of microvascular and macrovascular complications - with the leading cause of mortality in diabetes being cardiovascular disease. Low-density lipoprotein cholesterol, along with non-high-density lipoprotein cholesterol and triglycerides are proven, modifiable risk factors for cardiovascular disease. This article will focus on lipid-lowering agents in individuals with diabetes. It will summarise relevant changes in the latest guidelines for dyslipidaemia and will also review the mechanisms of action of lipid-lowering agents along with the latest cardiovascular outcomes data specific to individuals with diabetes. Older agents such as statins, ezetimibe, fibrates and nicotinic acid will be reviewed with a focus on new diabetes-specific evidence. Similarly, a relatively novel agent proprotein-convertase subtilisin-kexin type 9 will be reviewed and details around the Pharmaceutical Benefits Scheme criteria governing its usage in Australia will be reported. Finally, this review will touch on agents still on the horizon such as icosapent ethyl, high-density lipoprotein mimetics, bempedoic acid, omega-3 free fatty acids, bromodomain and extra-terminal protein inhibitors and inclisiran - a long-acting ribonucleic acid interference agent. In the appropriately selected population of individuals with diabetes, these agents can assist to improve further lipid profile and reduce cardiovascular events.

Relationship between omega-3 and omega-6 serum free fatty acids and ovarian reserve

Relationship between omega-3 and omega-6 serum free fatty acids and ovarian reserve

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

Evaluation of the possible therapeutic role of omega-3 on ankle joint and lung in a model of rheumatoid arthritis in rats: A histological and immunohistochemical study

ABSTRACTIntroduction: Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease. Lung disease has beenrecognized as a common complication of RA. Omega-3 is an essential fatty acid with wide range of activity.Aim of the work: To investigate the possible therapeutic role of omega-3 free fatty acid on the structure of ankle joint andlung in a model of adjuvant-induced RA in rats.Materials and Methods: Thirty adult male albino rats were divided into three groups; Group I served as a control group.Group II was used as a model of RA. Rats of this group were given single subcutaneous injection of 0.1ml of completeFreund adjuvant in their hind paws. Group III (omega 3-treated group), omega-3 was given in as a dose of 300 mg/kg orallyadministered after two weeks of RA induction and continued daily for another two weeks. The ankle joint and the lungs fromall groups were dissected out after two and four weeks and processed for light microscopic examination. Histomorphometricstudies and statistical analysis were also done.Results: RA was confirmed histologically in the ankle joint after two weeks and was aggravated after four weeks. Erosionof articular cartilage and mononuclear cellular infiltration in the synovium were noticed in both time points. Moreover, thelungs after two weeks showed focal inflammatory cellular infiltration and pulmonary fibrosis that were more evident afterfour weeks of untreated RA. This was associated with significant increase in the mean area percentage of collagen fibers andnumber of cells positive for TNF-α immunohistochemical reaction compared to the control group. Omega-3 treated groupillustrated improvement of both ankle and lung structures.Conclusion: Omega-3 significantly ameliorated the structural damage of ankle joint and lung after RA induction.

Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation

High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin. Knockdown Shp2 by siRNA resulted in significantly elevated omega-3 FFAs–activated Akt phosphorylation but failed to change insulin-stimulated Akt and Erk1/2 phosphorylation. And viable cell number was not affected by either downregulation of Shp2 expression or Erk1/2 inhibitor U0126 treatment. These observations indicated that omega-3 FFAs attenuate insulin-promoted breast cancer cell proliferation and insulin-activated Akt phosphorylation.

Development of an up-grading process to produce MLM structured lipids from sardine discards.

The aim of the work was to produce MLM structured lipids with caprylic acid (M) as medium chain fatty acid located at the external bonds of the glycerol backbone and concentrated polyunsaturated fatty acids (L) from sardine discards (Sardine pilchardus) in the central bond of the glycerol. To that end, the following steps were conducted: (i) fish oil extraction, (ii) Omega-3 free fatty acids (FFA) concentration (low temperature winterization), (iii) two-steps enzymatic esterification and (iv) triacylglycerols (TAG) purification (liquid column chromatography). The resultant purified triacylglycerols accomplished with the oxidative state (peroxide and anisidine value, PV and AV) required for refined oils. As enzymatic treatment, Omega-3 concentrate FFA (Omega-3>600mg Omega-3 per g oil) were esterified with dicaprylic glycerol employing Novozyme 435. This process presented high regioselectivity, with ∼80mol% of concentrated fatty acids esterified at the sn-2 position.

25 Modulation of Esophageal Inflammation in Obese Barrett's Esophagus Subjects by Omega-3 Free Fatty Acids: A Potential Strategy for Prevention of Esophageal Adenocarcinoma

25 Modulation of Esophageal Inflammation in Obese Barrett's Esophagus Subjects by Omega-3 Free Fatty Acids: A Potential Strategy for Prevention of Esophageal Adenocarcinoma

Anticipation Runs High for Coming Megatrials in General Cardiology

trials due to r Preventive cardiovascular medicine will get a big boost from ongoing major randomized controlled eport results during the next several years, Eric D. Peterson, MD, MPH, predicted at the annual meeting of the American College of Cardiology in San Diego. He presented an overview of eagerly anticipated clinical trials approaching completion in three of the hottest areas of research in general cardiology: new cardiovascular disease prevention agents and strategies; innovative health policy initiatives; and optimal antithrombotic regimens across the range of chronic coronary artery disease, peripheral arterial disease, patients with atrial fibrillation who’ve undergone percutaneous coronary intervention, and cerebrovascular disease. Dr. Peterson is executive director of the Duke Clinical Research Institute (DCRI), and professor of medicine at Duke University in Durham, N C.

Omega-3 free fatty acids inhibit tamoxifen-induced cell apoptosis

Fish oil, which contains omega-3 fatty acids mainly in the form of triglycerides, has benefits for reducing breast cancer risk, similar to tamoxifen action. However, it remains to be elucidated whether the combination of omega-3 free fatty acid (ω-3FFA) with tamoxifen leads to improved treatment in breast cancer. In this study, we observed that ω-3FFA induces MCF-7 cell apoptosis to suppress cell growth. The treatment of breast cancer cells with ω-3FFA attenuated tamoxifen-induced cell apoptosis. ω-3FFA and tamoxifen significantly increased Erk1/2 and Akt phosphorylation levels in a dose and time dependent manner. Compared to ω-3FFA alone, the combination of tamoxifen with ω-3FFA significantly increased Erk1/2 and Akt phosphorylation levels. Because Erk1/2 and Akt activation has been linked to tamoxifen-related anti-estrogen resistance in breast cancer patients, these results indicate that ω-3FFA may interfere with the effects of tamoxifen in the prevention of breast cancer risk.

Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model.

Beneficial effects of dietary supplements in age-related macular degeneration (AMD) are related to antioxidative properties. In the Age-Related Eye Disease Study 1 (AREDS 1), a reduced progression to late stage AMD was found using vitamin C, E, zinc, and β-carotene. We showed previously that the AREDS 1 formulation restores the O2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (lipopolysaccharide [LPS]) model. We hypothesized that the abnormal O2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (vitamin C, E, and zinc, lutein/zeaxanthin, selenium, taurine, Aronia extract, and omega-3 free fatty acids). A total of 43 healthy subjects was included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity, and flow to 100% O2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14-day period of daily dietary supplement intake. The decrease in retinal arterial diameter, RBC velocity, and flow during 100% O2 breathing was diminished significantly after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O2 after LPS administration. This effect was significant for retinal arterial diameter (P = 0.03 between groups), and RBC velocity and flow (each P < 0.01 between groups). The present data indicate restoring of the RBC flow response to 100% O2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology. (ClinicalTrials.gov number, NCT00914576.).

Influencing mitochondrial membrane composition and bioenergetics through omega-3 supplementation.

Influencing mitochondrial membrane composition and bioenergetics through omega-3 supplementation.

On-Treatment Triglyceride Concentration is a Determinant of the Change in LDL Particle Size During Therapy with Omega-3 Free Fatty Acids

On-Treatment Triglyceride Concentration is a Determinant of the Change in LDL Particle Size During Therapy with Omega-3 Free Fatty Acids

Plasma Fatty Acids as Predictors of Triglyceride and Non-HDL Cholesterol Responses to Omega-3 Free Fatty Acid Therapy in Hypertriglyceridemia

Plasma Fatty Acids as Predictors of Triglyceride and Non-HDL Cholesterol Responses to Omega-3 Free Fatty Acid Therapy in Hypertriglyceridemia

Oxidative stress markers in affective disorders

Affective disorders are a medical condition with a complex biological pattern of etiology, involving genetic and epigenetic factors, along with different environmental stressors. Increasing numbers of studies indicate that induction of oxidative and nitrosative stress (O&NS) pathways, which is accompanied by immune-inflammatory response, might play an important role in the pathogenic mechanisms underlying many major psychiatric disorders, including depression and bipolar disorder.Reactive oxygen and nitrogen species have been shown to impair the brain function by modulating activity of principal neurotransmitter (e.g., glutamatergic) systems involved in the neurobiology of depression. Both preclinical and clinical studies revealed that depression is associated with altered levels of oxidative stress markers and typically reduced concentrations of several endogenous antioxidant compounds, such as glutathione, vitamin E, zinc and coenzyme Q10, or enzymes, including glutathione peroxidase, and with an impairment of the total antioxidant status. These oxidative stress parameters can be normalized by successful antidepressant therapy. On the other hand, some antioxidants (zinc, N-acetylcysteine, omega-3 free fatty acids) may exhibit antidepressant properties or enhance standard antidepressant therapy. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present paper reviews selected animal and human studies providing evidence that oxidative stress is implicated in the pathophysiology and treatment of depression and bipolar disorder.