Effects Of Polyunsaturated Fatty Acids Research Articles

Association of Dietary Polyunsaturated Fatty Acid Intake with Allergic Rhinitis in Adults: A Cross-Sectional Study of NHANES 2005–2006

Introduction: The incidence of allergic rhinitis (AR) is increasing year by year, and the pathogenesis is complex, in which diet may play an important role. The role of polyunsaturated fatty acids (PUFAs) in AR is still controversial. Previous studies have looked at the effects of PUFA during pregnancy, childhood, and adolescence. In this study, we aimed to determine the association between dietary intake of PUFA and AR in adults. Methods: We used the NHANES database from 2005 to 2006 to include a total of 4,211 adult subjects. We collected dietary PUFA intake data and information on AR. Logistic regression and restricted cubic spline models were constructed to examine the association between PUFA intake and AR in adults. The t test was used to compare daily PUFA intakes in patients with and without AR. Results: In the fully adjusted model (OR: 1.016; 95% CI: 1.003; 1.028), PUFA intake was positively correlated with allergic symptoms, hay fever, and AR in adults (p < 0.05). In addition, daily PUFA intake was significantly higher in people with allergic symptoms, hay fever, and AR than in people without the disease (p < 0.01). Conclusions: Our results suggest a positive association between dietary PUFA intake and AR in adults to a certain extent. Future studies on dietary PUFA dose will provide new strategies for the prevention and treatment of allergic diseases such as AR related to non-pharmaceutical interventions.

Multi‐omic network analysis identified betacellulin as a novel target of omega‐3 fatty acid attenuation of western diet‐induced nonalcoholic steatohepatitis

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi‐omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta‐analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR‐binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor–β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti‐inflammatory and anti‐fibrotic effects of ω3 PUFA on NASH.

Omega-3 Polyunsaturated Fatty Acids and Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint contamination, pain, and damage. The study of animal RA debris is complicated and multifactorial, and has connections with hereditary, material, and immunological determinants. Omega-3 polyunsaturated fatty acids (PUFA) have gained much interest for their potential to treat RA because of their antagonistic, angiogenic, and immunomodulatory properties.Omega-3 PUFAs, found in fatty fish, flax seeds, and walnuts, include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These greasy acids have been demonstrated to weaken contamination by restraining pro-instigative cytokines, chemokines, and movable adhesion particles. In addition, they increase the results of anti-angering mediators and defeat sensitivity, contributing to joint security in RA. Medical research fact-finding on the effects of end-3 PUFAs on RA has proven promising. Supplementation with bait lubricate rich in EPA and DHA has been associated with lowered affliction ventures, diminished soft and swollen junctures, and diminished use of nonsteroidal antagonistic-angering drugs (NSAIDs). Additionally, omega-3 PUFAs have been shown to decrease inflexibility and improve overall growth in patients with RA. Despite irresistible evidence, the optimal portion of drugs or other consumables, endings, and forms of end-3 PUFA supplementation in RA are areas of ongoing study. Furthermore, the best randomized, regulated tests are needed to decode unending benefits and unfavorable belongings. In conclusion, end-3 PUFAs offer a promising secondary situation for RA, providing an unrefined and reliable method for directing contamination and improving welfare for individuals suffering from this incapacitating condition. Further research will increase our understanding of their duties in the context of RA and manual clinical recommendations for their use. Keywords: Omega-3 PUFA, Rheumatoid arthritis, swelling Autoimmune ailment, Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA), antagonistic-inflammatory and immunomodulatory Interest in joint care

Mendelian Randomization Analysis Reveals Causal Effects of Polyunsaturated Fatty Acids on Subtypes of Diabetic Retinopathy Risk.

Polyunsaturated fatty acids (PUFAs) affect several physiological processes, including visual acuity, but their relationship with diabetic retinopathy (DR) remains elusive. The aim of this study was to determine whether PUFAs have a causal effect on DR. PUFAs- (total and omega-3 [FAw3] and omega-6 [FAw6] fatty acids and their ratio) and DR-associated single nucleotide polymorphisms derived from genome-wide association studies; sample sizes were 114,999 for fatty acids and 216,666 for any DR (ADR), background DR (BDR), severe non-proliferative DR (SNPDR), and proliferative DR (PDR). We hypothesized that the intra-body levels of PUFAs have an impact on DR and conducted a two-sample Mendelian randomization (MR) study to assess the causality. Pleiotropy, heterogeneity, and sensitivity analyses were performed to verify result reliability. High levels of PUFAs were found to be associated with reduced risk of both ADR and PDR. Moreover, FAw3 was associated with a decreased risk of PDR, whereas FAw6 demonstrated an association with lowered risks of both BDR and PDR. Our findings provide genetic evidence, for the first time, for a causal relationship between PUFAs and reduced DR risk. Consequently, our comprehensive MR analysis strongly urges further investigation into the precise functions and long-term effects of PUFAs, FAw3, and FAw6 on DR.

Evaluating the Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Bowel Disease via Circulating Metabolites: A Mediation Mendelian Randomization Study.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Comparison of the Effects of Monounsaturated Fatty Acids and Polyunsaturated Fatty Acids on Liver Lipid Disorders in Obese Mice.

Obesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.

Omega-3 Polyunsaturated Fatty Acids Protect Neurological Function After Traumatic Brain Injury by Suppressing Microglial Transformation to the Proinflammatory Phenotype and Activating Exosomal NGF/TrkA Signaling.

The transformation of microglia to a pro-inflammatory phenotype at the site of traumatic brain injury (TBI) drives the progression of secondary neurodegeneration and irreversible neurological impairment. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to suppress this phenotype transformation, thereby reducing neuroinflammation following TBI, but the molecular mechanisms are unknown. We found that Omega-3 PUFA suppressed the expression of disintegrin metalloproteinase (ADAM17), the enzyme required to convert tumor necrosis factor-α (TNF-α) to the soluble form, thereby inhibiting the TNF-α/NF-κB pathway both in vitro and in a mouse model of TBI. Omega-3 PUFA also prevented the reactive transformation of microglia and promoted the secretion of microglial exosomes containing nerve growth factor (NGF), activating the neuroprotective NGF/TrkA pathway both in culture and TBI model mice. Moreover, Omega-3 PUFA suppressed the pro-apoptotic NGF/P75NTR pathway at the TBI site and reduced apoptotic neuronal death, brain edema, and disruption of the blood-brain barrier. Finally, Omega-3 PUFA preserved sensory and motor function as assessed by two broad-spectrum test batteries. The beneficial effects of Omega-3 PUFA were blocked by an ADAM17 promotor and by a NGF inhibitor, confirming the pathogenic function of ADAM17 and the central neuroprotective role of NGF. Collectively, these findings provide a strong experimental basis for Omega-3 PUFA as a potential clinical treatment for TBI.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer’s dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

Alzheimer’s dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500–2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84–4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Peroxisome proliferator-activated receptors mediate phytochemical-induced upregulation of farnesoid X receptor expression and activity in colonic epithelial cells

Introduction: The nuclear bile acid receptor, farnesoid X receptor (FXR), is expressed on intestinal epithelial cells where its potential as a new drug target for treatment of intestinal and metabolic disorders, such as chronic diarrhoea, colitis, colon cancer, obesity and diabetes, has been well-established. We have previously shown that pentacyclic triterpenes (PCTs), a class of dietary phytochemical, enhance the expression and activity of colonic epithelial FXR. Here, we investigated if another common class of dietary phytochemical, polyunsaturated fatty acids (PUFAs), also modulate FXR signalling in these cells. Furthermore, since peroxisome proliferator-activated receptors (PPARs) have been shown to regulate FXR expression in other cell types, we investigated their potential in mediating the effects of PCTs and PUFAs on FXR expression in the colonic epithelium. Methods: All experiments were conducted on monolayers of T 84 colonic epithelial cells grown on permeable supports. Alpha-linolenic acid (ALA; 100 μM) and hederagenin (HG; 5 μM) were used as prototypical PUFAs or PCTs, respectively. Rosiglitazone (1 μM) and WY14643 (1 – 20 μM) were employed as PPARγ and PPARα agonists, whereas GW9662 (20 μM) and GW6471 (1 μM) were used as PPARγ and PPARα antagonists, respectively. Levels of FXR, FGF19, an index of FXR activation, and ANGPTL4, a PPAR target gene, were measured by qRT-PCR, western blotting, or ELISA. Results: Similar to our previous studies with HG, treatment of T 84 cells with ALA upregulated FXR mRNA and protein expression to 11.43 ± 2.1 fold (n = 7, p &lt; 0.01) and 6.4 ± 1.2 fold (n = 6, p &lt; 0.05) of that in control cells, respectively. ALA treatment also enhanced the effects of an FXR agonist, GW4064 (5 μM), on FGF19 mRNA and protein expression by 4.4 ± 1.6 (n = 7) and 6.5 ± 1.4 fold (n = 8, p &lt; 0.05), respectively. Treatment with HG and ALA (3 hrs) also increased mRNA expression of the PPAR target gene, ANGPTL4, to 5.7 ± 1.0 (n = 5; p &lt; 0.05) and 66.3 ± 9.5 fold (n = 7; p &lt; 0.01) of that in untreated cells, respectively. Furthermore, the effects of the phytochemicals on FXR expression were mimicked by the PPARγ and PPARα agonists, rosiglitazone and WY14643, respectively. The PPARγ antagonist, GW9662, inhibited ALA-induced FXR mRNA expression by 0.5 ± 0.1 fold (n = 11; p &lt; 0.001) but did not alter responses to HG. In contrast, the PPARα antagonist, GW6471, inhibited both ALA and HG-induced FXR mRNA expression by 0.71 ± 0.1 and 0.58 ± 0.1 fold (n = 4; p &lt; 0.05) of that in control cells, respectively. Conclusion: The dietary phytochemicals, HG and ALA, upregulate colonic epithelial FXR through mechanisms that appear to involve differential activation of PPARs. By virtue of their ability to upregulate FXR expression and activity, foods or food supplements, rich in such PCTs and PUFAs have excellent potential for development as a new class of “FXR-targeted nutraceutical” for treatment and prevention of intestinal and metabolic disorders. Science Foundation Ireland This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The potential effects of polyunsaturated ω-3 fatty acids on spinal cord injury: A systematic review & meta-analysis of preclinical evidence.

Polyunsaturated fatty acids (PUFAs) have received attention for their anti-inflammatory and antioxidant properties. Preclinical studies have investigated the efficacy of PUFAs in animal models of spinal cord injury (SCI) to determine if these properties can translate to neuroprotection and locomotor recovery. Findings from such studies have been promising, suggesting PUFAs as potential treatments against the neurological dysfunction induced by SCI. This systematic review and meta-analysis sought to investigate the efficacy of PUFAs for promoting locomotor recovery in animal models of SCI. PubMed, Web of Science and Embase (Ovid) were searched for relevant papers and those that examined the restorative effects of PUFAs on locomotor recovery in preclinical SCI models were included in our analysis. A random effects meta-analysis (restricted maximum likelihood estimator) was employed. A total of 28 studies were included and the results showed the claim that PUFAs have a beneficial therapeutic effect for promoting locomotor recovery (SMD=1.037, 95% CI=0.809-1.2644, p=<0.001) and cell survival (SMD=1.101, 95% CI=0.889-1.313, p=<0.001) in animal models of SCI. No significant differences for the secondary outcomes of neuropathic pain and lesion volume. Moderate asymmetry was observed in the funnel plots for locomotor recovery, cell survival and neuropathic pain measures, suggesting publication bias. Trim-and-fill analysis estimated 13, 3, 0 and 4 missing studies for locomotor recovery, cell survival, neuropathic pain, and lesion volume, respectively. A modified CAMARADES checklist was also used to assess risk of bias, showing that the median score for all included papers was 4 out of a possible 7.

Effects of Whey Protein, Omega-3 Fatty Acid and Roux-En-Y Gastric Bypass on Body Weight, Biochemical Parameters and Organ Functions in an Obese Rat Model: Experimental Research

Extreme obesity (EO) is one of the biggest public health problems in the world and has grown considerably over the years. The aim of the study is to examine the effect of Roux-en-Y gastric bypass (RYGB), whey protein (WP), and omega-3 polyunsaturated fatty acid (PUFA) supplementation applied to EO rats on weight loss, histopathological changes in internal organs and biochemical alterations. Wistar albino female rats (n = 28) were used in the study and randomly divided into four groups. All rats were made obese by adding high fructose corn syrup (HFCS) to their drinking water. After the EO, WP and omega-3 PUFA supplementation was given and RYGB process was applied. At the end of the study, glucose, total cholesterol, HDL, VLDL, AST, ALT and uric acid changes and liver, kidney and pancreatic tissues were evaluated histopathologically. WP and omega-3 PUFA supplementation decreased body weight (p > 0.05). Omega-3 PUFA and RYGB caused a decrease in total cholesterol (p < 0.05), WP decreased HDL (p < 0.05), WP and omega-3 PUFA caused an increase in ALT (p < 0.05). WP has been shown to have greater curative effects in rat liver and kidney tissues. It has been determined that RYGB causes necrosis in the liver and HFCS causes inflammation in the kidney. In the study; the positive effects of WP, omega-3 PUFA and bariatric surgery on obesity and dyslipidemia have been demonstrated. With this result, it was determined that WP, omega-3 PUFA supplementation and bariatric surgery were not superior to each other.

Differential Behavior of Eicosapentaenoic and Docosahexaenoic Acids on the Organization, Dynamics, and Fusion of Homogeneous and Heterogeneous Membranes.

Membrane fusion is a common course in innumerable biological processes that helps in the survival of eukaryotes. Enveloped viruses utilize this process to enter the host cells. Generally, the membrane lipid compositions play an important role in membrane fusion by modulating the membrane's physical properties and the behavior of membrane proteins in the cellular milieu. In this work, we have demonstrated the role of polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on the organization, dynamics, and fusion of homogeneous and heterogeneous membranes. We have exploited arrays of steady-state and time-resolved fluorescence spectroscopic methods and polyethylene glycol-induced membrane fusion assay to elucidate the behavior of EPA and DHA on dioleoyl phosphatidylcholine (DOPC)/cholesterol (CH) homogeneous and DOPC/sphingomyelin/CH heterogeneous membranes. Our results suggest that EPA and DHA display differential effects on two different membranes. The effects of PUFAs in homogeneous membranes are majorly attributed to their flexible chain dynamics, whereas the ability of PUFA-induced cholesterol transfer from the lo to the ld phase rules their behavior in heterogeneous membranes. Overall, our results provide detailed information on the effect of PUFAs on homogeneous and heterogeneous membranes.

Pharmacological Potentials of Omega 3 Fatty Acid in Reduction of Atrial Fibrillation

Atrial fibrillation (AF) is the most common type of arrhythmia in the general population with a prevalence that reaches one third of patients with arterial hypertension, diabetic and other risk factors. In atrial fibrillation, the regular impulses produced by the sinus node for a normal heart beat are overwhelmed by rapid electrical discharges produced in the atria and adjacent parts of the pulmonary veins. Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. It has been proposed that Omega-3 polyunsaturated fatty acid possess anti-inflammatory properties that can inhibit arrhythmogenic mechanisms. Potential Targets of Omega-3 PUFAs Relevant to Arrhythmias Prevention are direct inhibition of sarcolemmal ion channels &amp; restoring cardiac connexion channels. Intake of omega-3 fatty acids significantly prevents the occurrence of AF. The purpose of this review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of atrial fibrillation.&#x0D; Keywords: Eicosapentaenoic acid, Docosahexaenoic acid, Atrial Fibrillation, Polyunsaturated fatty acids, Arrhythmias.

Effect of Polyunsaturated Fatty Acids on Temozolomide Drug-Sensitive and Drug-Resistant Glioblastoma Cells.

Glioblastomas (GBMs) are notoriously difficult to treat, and the development of multiple drug resistance (MDR) is common during the course of the disease. The polyunsaturated fatty acids (PUFAs) gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have been reported to improve MDR in several tumors including breast, bladder, and leukaemia. However, the effects of PUFAs on GBM cell MDR are poorly understood. The present study investigated the effects of PUFAs on cellular responses to temozolomide (TMZ) in U87MG cells and the TMZ-resistant (TMZR) cells derived from U87MG. Cells were treated with PUFAs in the absence or presence of TMZ and dose-response, viable cell counting, gene expression, Western blotting, flow cytometry, gas chromatography-mass spectrometry (GCMS), and drug efflux studies were performed. The development of TMZ resistance caused an increase in ABC transporter ABCB1 and ABCC1 expression. GLA-, EPA-, and DHA-treated cells had altered fatty acid composition and accumulated lipid droplets in the cytoplasm. The most significant reduction in cell growth was seen for the U87MG and TMZR cells in the presence of EPA. GLA and EPA caused more significant effects on ABC transporter expression than DHA. GLA and EPA in combination with TMZ caused significant reductions in rhodamine 123 efflux from U87MG cells but not from TMZR cells. Overall, these findings support the notion that PUFAs can modulate ABC transporters in GBM cells.

Effect of Short-Chain Fatty Acids and Polyunsaturated Fatty Acids on Metabolites in H460 Lung Cancer Cells

Lung cancer is the most common primary malignant lung tumor. However, the etiology of lung cancer is still unclear. Fatty acids include short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) as essential components of lipids. SCFAs can enter the nucleus of cancer cells, inhibit histone deacetylase activity, and upregulate histone acetylation and crotonylation. Meanwhile, PUFAs can inhibit lung cancer cells. Moreover, they also play an essential role in inhibiting migration and invasion. However, the mechanisms and different effects of SCFAs and PUFAs on lung cancer remain unclear. Sodium acetate, butyrate, linoleic acid, and linolenic acid were selected to treat H460 lung cancer cells. Through untargeted metabonomics, it was observed that the differential metabolites were concentrated in energy metabolites, phospholipids, and bile acids. Then, targeted metabonomics was conducted for these three target types. Three LC-MS/MS methods were established for 71 compounds, including energy metabolites, phospholipids, and bile acids. The subsequent methodology validation results were used to verify the validity of the method. The targeted metabonomics results show that, in H460 lung cancer cells incubated with linolenic acid and linoleic acid, while the content of PCs increased significantly, the content of Lyso PCs decreased significantly. This demonstrates that there are significant changes in LCAT content before and after administration. Through subsequent WB and RT-PCR experiments, the result was verified. We demonstrated a substantial metabolic disparity between the dosing and control groups, further verifying the reliability of the method.

Trophic transfer of polyunsaturated fatty acids across the aquatic-terrestrial interface: An experimental tritrophic food chain approach.

Aquatic and their adjacent terrestrial ecosystems are linked via the flux of organic and inorganic matter. Emergent aquatic insects are recognized as high-quality food for terrestrial predators, because they provide more physiologically relevant long-chain polyunsaturated fatty acids (PUFA) than terrestrial insects. The effects of dietary PUFA on terrestrial predators have been explored mainly in feeding trials conducted under controlled laboratory conditions, hampering the assessment of the ecological relevance of dietary PUFA deficiencies under field conditions. We assessed the PUFA transfer across the aquatic-terrestrial interface and the consequences for terrestrial riparian predators in two outdoor microcosm experiments. We established simplified tritrophic food chains, consisting of one of four basic food sources, an intermediary collector gatherer (Chironomus riparius, Chironomidae), and a riparian web-building spider (Tetragnatha sp.). The four basic food sources (algae, conditioned leaves, oatmeal, and fish food) differed in PUFA profiles and were used to track the trophic transfer of single PUFA along the food chain and to assess their potential effects on spiders, that is, on fresh weight, body condition (size-controlled measurement of nutritional status), and immune response. The PUFA profiles of the basic food sources, C.riparius and spiders differed between treatments, except for spiders in the second experiment. The PUFA α-linolenic acid (ALA, 18:3n-3) and ɣ-linolenic acid (GLA, 18:3n-6) were major contributors to the differences between treatments. PUFA profiles of the basic food sources influenced the fresh weight and body condition of spiders in the first experiment, but not in the second experiment, and did not affect the immune response, growth rate, and dry weight in both experiments. Furthermore, our results indicate that the examined responses are dependent on temperature. Future studies including anthropogenic stressors would deepen our understanding of the transfer and role of PUFA in ecosystems.

The role of omega-3 polyunsaturated fatty acids in the intensive care unit.

This review provides an update on the actions of omega-3 polyunsaturated fatty acids (PUFAs) and presents the most recent findings from trials in patients in the intensive care unit (ICU) setting including relevant meta-analyses. Many specialized pro-resolving mediators (SPMs) are produced from bioactive omega-3 PUFAs and may explain many of the beneficial effects of omega-3 PUFAs, although other mechanisms of action of omega-3 PUFAs are being uncovered. SPMs resolve inflammation, promote healing and support antiinfection activities of the immune system. Since publication of the ESPEN guidelines, numerous studies further support the use of omega-3 PUFAs. Recent meta-analyses favor the inclusion of omega-3 PUFAs in nutrition support of patients with acute respiratory distress syndrome or sepsis. Recent trials indicate that omega-3 PUFAs may protect against delirium and liver dysfunction in patients in the ICU, although effects on muscle loss are unclear and require further investigation. Critical illness may alter omega-3 PUFA turnover. There has been significant discussion about the potential for omega-3 PUFAs and SPMs in treatment of coronavirus disease 2019. Evidence for benefits of omega-3 PUFAs in the ICU setting has strengthened through new trials and meta-analyses. Nevertheless, better quality trials are still needed. SPMs may explain many of the benefits of omega-3 PUFAs.

Associations between polyunsaturated fatty acid concentrations and Parkinson's disease: A two-sample Mendelian randomization study.

Observational studies demonstrated controversial effect of polyunsaturated fatty acids (PUFAs) on Parkinson's disease (PD) with limited causality evidence. Randomized control trials showed possible improvement in PD symptoms with PUFA supplement but had small study population and limited intervention time. A two-sample Mendelian randomization was designed to evaluate the causal relevance between PUFAs and PD, using genetic variants of PUFAs as instrumental variables and PD data from the largest genome-wide association study as outcome. Inverse variance weighted (IVW) method was applied to obtain the primary outcome. Mendelian randomization Egger regression, weighted median and weighted mode methods were exploited to assist result analyses. Strict Mendelian randomization and multivariable Mendelian randomization (MVMR) were used to estimate direct effects of PUFAs on PD, eliminating pleiotropic effect. Debiased inverse variance weighted estimator was implemented when weak instrument bias was introduced into the analysis. A variety of sensitivity analyses were utilized to assess validity of the results. Our study included 33,674 PD cases and 449,056 controls. Higher plasma level of arachidonic acid (AA) was associated with a 3% increase of PD risk per 1-standard deviation (SD) increase of AA (IVW; Odds ratio (OR)=1.03 [95% confidence interval (CI) 1.01-1.04], P = 2.24E-04). After MVMR (IVW; OR=1.03 [95% CI 1.02-1.04], P =6.15E-08) and deletion of pleiotropic single-nucleotide polymorphisms overlapping with other lipids (IVW; OR=1.03 [95% CI 1.01-1.05], P =5.88E-04), result was still significant. Increased level of eicosapentaenoic acid (EPA) showed possible relevance with increased PD risk after adjustment of pleiotropy (MVMR; OR=1.05 [95% CI 1.01-1.08], P =5.40E-03). Linoleic acid (LA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were found not causally relevant to PD risk. Various sensitivity analyses verified the validity of our results. In conclusion, our findings from Mendelian randomization suggested that elevated levels of AA and possibly EPA might be linked to a higher risk of PD. No association between PD risk and LA, DHA, DPA, or ALA was found. The odds ratio for plasma AA and PD risk was weak. It is important to approach our results with caution in clinical practice and to conduct additional studies on the relationship between PUFAs and PD risk.

Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis.

There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD = -6.72 IU/L; 95% CI: -8.61, -4.84; p< 0.001, and ESSMD = -0.52 IU/L; 95% CI: -0.84, -0.20, p< 0.001), AST (ESWMD = -3.73 IU/L, 95% CI: -5.93, -1.53, p< 0.001, and ESSMD = -0.65 IU/L; 95% CI: -1.08, -0.22, p= 0.003), GGT levels (ESWMD = -4.20 IU/L, 95% CI: -6.85, -1.55, p= 0.002), and liver fat (ESWMD = -5.16; 95% CI: -8.49, -1.82, p< 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.

Investigating the mechanism behind the effect of PUFA analogues in increasing the maximum conductance of KCNQ1 channels.

Polyunsaturated fatty acids (PUFAs) are potent activators of KCNQ1 channels, found in smooth muscle cells and cardiomyocytes. In the latter, the channel forms the KCNQ1/KCNE1 complex, mediating the slow delayed-rectifier currents (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause Long QT Syndrome (LQT), which increases the risk of sudden cardiac death and ventricular arrhythmia. One possible therapeutic intervention would be based on specifically targeting IKs currents to restore the channel function and the physiological QT interval. PUFAs are ideal candidates as they activate IKs current by shifting the voltage dependence of opening toward negative voltages and by increasing the maximum conductance of the channel (Gmax). PUFAs mechanism of action rely on two different binding sites, one at the voltage sensor domain - which shifts the voltage dependence - and the other at the pore region of the channel - which increases the Gmax. However, the mechanism by which PUFAs increase the Gmax of the channels is still poorly understood. In this study, we propose that the increase in the channel currents is caused by a complex mechanism of several residues in the external mouth of the pore, including K326, P320, and the two tryptophans of the conserved aromatic ring cuff. Our investigations showed that by mutating some of these residues, the effect of PUFAs on Gmax is reduced, describing a complex mechanism involving a wide network of residues in the Gmax effect of PUFAs.