-
Mediators of Inflammation 2021Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In... (Review)
Review
Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs-microbiome-immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.
Topics: Animals; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Gastrointestinal Microbiome; Humans; Intestines
PubMed: 33488295
DOI: 10.1155/2021/8879227 -
Genomics, Proteomics & Bioinformatics Oct 2021Oleic acid (OA), a monounsaturated fatty acid (MUFA), has previously been shown to reverse saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance...
Oleic acid (OA), a monounsaturated fatty acid (MUFA), has previously been shown to reverse saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance (IR). However, its underlying molecular mechanism is unclear. In addition, previous studies have shown that eicosapentaenoic acid (EPA), a ω-3 polyunsaturated fatty acid (PUFA), reverses PA-induced muscle IR, but whether EPA plays the same role in hepatic IR and its possible mechanism involved need to be further clarified. Here, we confirmed that EPA reversed PA-induced IR in HepG2 cells and compared the proteomic changes in HepG2 cells after treatment with different free fatty acids (FFAs). A total of 234 proteins were determined to be differentially expressed after PA+OA treatment. Their functions were mainly related to responses to stress and endogenous stimuli, lipid metabolic process, and protein binding. For PA+EPA treatment, the PA-induced expression changes of 1326 proteins could be reversed by EPA, 415 of which were mitochondrial proteins, with most of the functional proteins involved in oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle. Mechanistic studies revealed that the protein encoded by JUN and reactive oxygen species (ROS) play a role in OA- and EPA-reversed PA-induced IR, respectively. EPA and OA alleviated PA-induced abnormal adenosine triphosphate (ATP) production, ROS generation, and calcium (Ca) content. Importantly, HO-activated production of ROS increased the protein expression of JUN, further resulting in IR in HepG2 cells. Taken together, we demonstrate that ROS/JUN is a common response pathway employed by HepG2 cells toward FFA-regulated IR.
Topics: Eicosapentaenoic Acid; Hep G2 Cells; Humans; Hydrogen Peroxide; Insulin Resistance; Oleic Acid; Palmitic Acid; Proteomics; Reactive Oxygen Species
PubMed: 33631425
DOI: 10.1016/j.gpb.2019.06.005 -
Medicina (Kaunas, Lithuania) Jul 2022: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of... (Review)
Review
: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of nutritional interventions aiming to improve cachexia outcomes in cancer, focusing on weight gain. : A search in Medline and Elsevier databases for articles up until the 23 January 2022, was conducted. : Out of 5732 screened records, 26 publications were included in the final analysis. Four randomized clinical trials showed a significant body weight (BW) increase in patients treated with eicosapentaenoic acid (EPA), β-hydroxy-beta-methyl butyrate (β-HMB), arginine, and glutamine or marine phospholipids (MPL). An upward BW trend was observed in patients treated with L-carnitine, an Ethanwell/Ethanzyme (EE) regimen enriched with ω-3 fatty acids, micronutrients, probiotics, fish oil, a leucine-rich supplement, or total parental nutrition (TPN) with a high dose of a branched-chain amino acid (BCAA). : Although clinical trials relating to large numbers of nutritional supplements present promising data, many trials provided negative results. Further studies investigating the underlying mechanisms of action of these nutritional supplements in cancer cachexia are needed. Early screening for cancer cachexia risk and nutritional intervention in cancer patients before aggravating weight loss may stabilize their weight, preventing cachexia syndrome. According to the GRADE methodology, no positive recommendation for these nutritional supplements may be expressed.
Topics: Cachexia; Dietary Supplements; Eicosapentaenoic Acid; Humans; Micronutrients; Neoplasms
PubMed: 35888685
DOI: 10.3390/medicina58070966 -
Annual Review of Pharmacology and... Jan 2023The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood, supplements, and concentrated pharmaceutical... (Review)
Review
The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in seafood, supplements, and concentrated pharmaceutical preparations. Prospective cohort studies demonstrate an association between higher intakes of EPA+DHA or higher levels of EPA and DHA in the body and lower risk of developing cardiovascular disease (CVD), especially coronary heart disease and myocardial infarction, and of cardiovascular mortality in the general population. The cardioprotective effect of EPA and DHA is due to the beneficial modulation of a number of risk factors for CVD. Some large trials support the use of EPA+DHA (or EPA alone) in high-risk patients, although the evidence is inconsistent. This review presents key studies of EPA and DHA in the primary and secondary prevention of CVD, briefly describes potential mechanisms of action, and discusses recently published RCTs and meta-analyses. Potential adverse aspects of long-chain omega-3 fatty acids in relation to CVD are discussed.
Topics: Humans; Prospective Studies; Fatty Acids, Omega-3; Cardiovascular System; Docosahexaenoic Acids; Eicosapentaenoic Acid; Cardiovascular Diseases
PubMed: 36662586
DOI: 10.1146/annurev-pharmtox-051921-090208 -
International Journal of Molecular... Dec 2017In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow... (Review)
Review
In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.
Topics: Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Psychotic Disorders
PubMed: 29207548
DOI: 10.3390/ijms18122608 -
Autophagy Jul 2021Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the...
Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the renovation of plasma and organelle membranes to maintain the integrity of the PTECs. However, this autophagic activation places a burden on the lysosomal system, leading to a downstream suppression of autophagy, which manifests as phospholipid accumulation and inadequate acidification in lysosomes. Here, we investigated whether pharmacological correction by eicosapentaenoic acid (EPA) supplementation could restore autophagic flux and alleviate renal lipotoxicity. EPA supplementation to high-fat diet (HFD)-fed mice reduced several hallmarks of lipotoxicity in the PTECs, such as phospholipid accumulation in the lysosome, mitochondrial dysfunction, inflammation, and fibrosis. In addition to improving the metabolic syndrome, EPA alleviated renal lipotoxicity via several mechanisms. EPA supplementation to HFD-fed mice or the isolated PTECs cultured in palmitic acid (PA) restored lysosomal function with significant improvements in the autophagic flux. The PA-induced redistribution of phospholipids from cellular membranes into lysosomes and the HFD-induced accumulation of SQSTM1/p62 (sequestosome 1), an autophagy substrate, during the temporal and genetic ablation of autophagy were significantly reduced by EPA, indicating that EPA attenuated the HFD-mediated increases in autophagy demand. Moreover, a fatty acid pulse-chase assay revealed that EPA promoted lipid droplet (LD) formation and transfer from LDs to the mitochondria for beta-oxidation. Noteworthy, the efficacy of EPA on lipotoxicity is autophagy-dependent and cell-intrinsic. In conclusion, EPA counteracts lipotoxicity in the proximal tubule by alleviating autophagic numbness, making it potentially suitable as a novel treatment for obesity-related kidney diseases. 4-HNE: 4-hydroxy-2-nonenal; ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; ATG: autophagy-related; ATP: adenosine triphosphate; BODIPY: boron-dipyrromethene; BSA: bovine serum albumin; cKO: conditional knockout; CML: N-carboxymethyllysine; COL1A1: collagen type I alpha 1 chain; COX: cytochrome c oxidase; CTRL: control; DGAT: diacylglycerol O-acyltransferase; EPA: eicosapentaenoic acid; FA: fatty acid; FFA: free fatty acid; GFP: green fluorescent protein; HFD: high-fat diet; iKO: inducible knockout; IRI: ischemia-reperfusion injury; LAMP1: lysosomal-associated membrane protein 1; LD: lipid droplet; LRP2: low density lipoprotein receptor-related protein 2; MAP1LC3: microtubule-associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; OA: oleic acid; PAS: periodic-acid Schiff; PPAR: peroxisome proliferator activated receptor; PPARGC1/PGC1: peroxisome proliferator activated receptor, gamma, coactivator 1; PTEC: proximal tubular epithelial cell; ROS: reactive oxygen species; RPS6: ribosomal protein S6; SDH: succinate dehydrogenase complex; SFC/MS/MS: supercritical fluid chromatography triple quadrupole mass spectrometry; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TG: triglyceride; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.
Topics: Acute Kidney Injury; Animals; Autophagy; Diet, High-Fat; Eicosapentaenoic Acid; Kidney; Kidney Tubules, Proximal; Lysosomes; Mice; Mice, Transgenic; Phospholipids
PubMed: 32546086
DOI: 10.1080/15548627.2020.1782034 -
Nutrients Mar 2021Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood. Blood levels of EPA and... (Review)
Review
Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood. Blood levels of EPA and DHA reflect dietary intake and other variables and are preferably assessed as percentage in erythrocytes with a well-documented and standardized analytical method (HS-Omega-3 Index). Every human being has an Omega-3 Index between 2 and 20%, with an optimum of 8-11%. Compared to an optimal Omega-3 Index, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies. Most intervention trials, and their meta-analyses considered EPA and DHA as drugs with good bioavailability, a design tending to produce meaningful results in populations characterized by low baseline blood levels (e.g., in major depression), but otherwise responsible for many neutral results and substantial confusion. When trial results were evaluated using blood levels of EPA and DHA measured, effects were larger than comparing EPA and DHA to placebo groups, and paralleled epidemiologic findings. This indicates future trial design, and suggests a targeted use EPA and DHA, based on the Omega-3 Index.
Topics: Brain; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans
PubMed: 33806218
DOI: 10.3390/nu13041074 -
Journal of the International Society of... Dec 2023Resistance exercise training (RET) is a common and well-established method to induce hypertrophy and improvement in strength. Interestingly, fish oil supplementation... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Resistance exercise training (RET) is a common and well-established method to induce hypertrophy and improvement in strength. Interestingly, fish oil supplementation (FOS) may augment RET-induced adaptations. However, few studies have been conducted on young, healthy adults.
METHODS
A randomized, placebo-controlled design was used to determine the effect of FOS, a concentrated source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), compared to placebo (PL) on RET-induced adaptations following a 10-week RET program (3 days·week). Body composition was measured by dual-energy x-ray absorptiometry (LBM, fat mass [FM], percent body fat [%BF]) and strength was measured by 1-repetition maximum barbell back squat (1RM) and bench press (1RM) at PRE (week 0) and POST (10 weeks). Supplement compliance was assessed via self-report and bottle collection every two weeks and via fatty acid dried blood spot collection at PRE and POST. An α-level of 0.05 was used to determine statistical significance and Cohen's was used to quantify effect sizes (ES).
RESULTS
Twenty-one of 28 male and female participants (FOS, = 10 [4 withdrawals]; PL, = 11 [3 withdrawals]) completed the 10-week progressive RET program and PRE/POST measurements. After 10-weeks, blood EPA+DHA substantially increased in the FOS group (+109.7%, < .001) and did not change in the PL group (+1.3%, = .938). Similar between-group changes in LBM (FOS: +3.4%, PL: +2.4%, = .457), FM (FOS: -5.2%, PL: 0.0%, = .092), and %BF (FOS: -5.9%, PL: -2.5%, = .136) were observed, although, the between-group ES was considered large for FM ( = 0.84). Absolute and relative (kg·kg [body mass]) 1RM was significantly higher in the FOS group compared to PL (FOS: +17.7% vs. PL: +9.7%, = .047; FOS: +17.6% vs. PL: +7.3%, = .011; respectively), whereas absolute 1RM was similar between conditions (FOS: +28.8% vs. PL: +20.5%, = .191). Relative 1RM was higher in the FOS group (FOS: +29.3% vs. PL: +17.9%, = .045).
CONCLUSIONS
When combined with RET, FOS improves absolute and relative 1RM upper-body and relative 1RM lower-body strength to a greater extent than that observed in the PL group of young, recreationally trained adults.
Topics: Female; Humans; Male; Body Composition; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fish Oils; Muscle Strength; Muscle, Skeletal; Resistance Training
PubMed: 36822153
DOI: 10.1080/15502783.2023.2174704 -
Advances in Nutrition (Bethesda, Md.) Jul 2023The current guidelines recommend that people consume 2 or more servings of fat-rich fish per week to obtain enough omega-3 (ω-3) polyunsaturated fatty acids to prevent... (Meta-Analysis)
Meta-Analysis Review
The current guidelines recommend that people consume 2 or more servings of fat-rich fish per week to obtain enough omega-3 (ω-3) polyunsaturated fatty acids to prevent cardiovascular events. However, the cardiovascular benefits of ω-3 polyunsaturated fatty acids in patients with diabetes are unclear, and related large-scale trials have produced conflicting results. We aimed to perform a meta-analysis of all randomized controlled trials that attempted to assess the effects of ω-3 fatty acid supplementation on cardiovascular outcomes in patients with diabetes. In PubMed, EMBASE, and the Cochrane Library, we searched for data from all randomized controlled trials on ω-3 fatty acids and cardiovascular outcomes in patients with diabetes published before July 2022. Eight eligible studies involving 57,754 participants were ultimately included. Meta-analysis showed that ω-3 fatty acid supplementation reduces cardiovascular disease (CVD) risk in patients with diabetes (rate ration [RR] = 0.93; 95% confidence interval [CI]: 0.90, 0.97; P = 0.0009). Among them, eicosapentaenoic acid (EPA), but not EPA plus docosahexaenoic acid (DHA), significantly reduced the risk of CVD in patients with diabetes (EPA [RR = 0.81; 95% CI: 0.73, 0.90; P=0.0001]). This meta-analysis suggests that ω-3 fatty acid supplementation is an effective strategy to prevent CVD in patients with diabetes, but further well-designed, large-scale randomized controlled trials are necessary to evaluate the safety of ω-3 fatty acid supplementation, and its effect on atrial fibrillation. This study was registered with PROSPERO as CRD42022346302.
Topics: Humans; Dietary Supplements; Randomized Controlled Trials as Topic; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Docosahexaenoic Acids; Diabetes Mellitus; Cardiovascular Diseases
PubMed: 37121469
DOI: 10.1016/j.advnut.2023.04.009 -
Pharmacology & Therapeutics Sep 2022Atherosclerotic cardiovascular disease (ASCVD) and its atherothrombotic complications impose a substantial disease burden in Europe, representing a cost of €210... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) and its atherothrombotic complications impose a substantial disease burden in Europe, representing a cost of €210 billion per year for the European Union. Hypertriglyceridemia, a major risk factor for premature ASCVD, is present in more than 20% of the European population, and is a key feature of atherogenic dyslipidemia. Recent findings from the Progression of Early Subclinical Atherosclerosis (PESA) cohort in Spain showed that even in apparently healthy, middle-aged individuals without a history of cardiovascular (CV) risk, elevated triglyceride levels are associated with subclinical atherosclerosis and arterial inflammation. Emerging evidence from epidemiologic and genetic studies supports an independent causative role of triglycerides, triglyceride-rich lipoproteins, and their remnants in this pathology. Icosapent ethyl (IPE) is a highly purified, stable ethyl ester of eicosapentaenoic acid (EPA) that was initially approved by the United States Food and Drug Administration to treat severe hypertriglyceridemia, and subsequently received an expanded indication to reduce the risk of CV events in adult statin-treated patients. Approval was based on the pivotal, randomized, placebo-controlled, double-blind Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), which showed that high-dose IPE (4 g/day) significantly reduced the risk of primary and secondary composite endpoints comprising major CV events and CV death relative to placebo. In 2021, the European Medicines Agency (EMA) approved IPE to reduce the risk of CV events in adult statin-treated patients at high CV risk with elevated triglyceride levels (≥1.7 mmol/L [≥150 mg/dL]) and established CV disease, or diabetes and at least one other CV risk factor. Clinical studies in Europe, which included patients with acute myocardial infarction, coronary artery disease, and those undergoing cardiac rehabilitation, established that 12.5% to 23.3% of these high-risk populations may benefit from treatment with IPE. Such clinical benefit may in part result from the moderate triglyceride-lowering properties of IPE/EPA; equally however, concentrations of atherogenic remnant particle-cholesterol are markedly reduced. Furthermore, IPE/EPA exerts pleiotropic actions beyond its lipid-lowering properties, which include modulation of endothelial function, attenuation of intra-plaque inflammation and oxidative stress, and reduction in macrophage accumulation. Plasma phospholipids, into which EPA is primarily incorporated and transported, appear to serve as precursors for a series of anti-inflammatory metabolites involving the resolvins RvE1 to RvE3, a pathway which may confer cardioprotective benefits. In addition, plaque imaging data from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) and the Combination Therapy of Eicosapentaenoic Acid and Pitavastatin for Coronary Plaque Regression Evaluated by Integrated Backscatter Intravascular Ultrasonography (CHERRY) trials show that plaque stabilization may be favorably affected. These factors may act synergistically to stabilize atherosclerotic plaques and reduce CV risk. In addition to robust efficacy data, multiple cost-utility studies across several countries indicate that IPE/EPA is a cost-effective treatment option that is favorably situated relative to some common willingness-to-pay thresholds. This review will evaluate the relevance of hypertriglyceridemia to residual ASCVD burden in statin-treated dyslipidemic patients, the potential of IPE/EPA to reduce the risk of ASCVD and cardiovascular mortality in high-risk patient populations, and the mechanisms which may underlie these effects. Finally, the clinical implications of the EMA label for IPE will be critically appraised in light of the updated 2019 European Society of Cardiology/European Atherosclerosis Society guidelines on the management of dyslipidemia and the recent European Atherosclerosis Society consensus statement on triglyceride-rich lipoproteins and their remnants, together with considerations of its cost-effectiveness across several countries.
Topics: Adult; Atherosclerosis; Cardiovascular Diseases; Coronary Artery Disease; Eicosapentaenoic Acid; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Lipoproteins; Middle Aged; Plaque, Atherosclerotic; Randomized Controlled Trials as Topic; Risk Factors; Triglycerides
PubMed: 35304222
DOI: 10.1016/j.pharmthera.2022.108172