Search Results (303)

Omega-6 polyunsaturated fats (ω-6 PUFAs) are vital for many physiological functions, but their impact on cardiovascular disease (CVD) risk is controversial. Eryptosis alters blood viscosity by providing a procoagulant surface and leads to anemia, which is a recognized risk factor for CVD. This study examines the toxic mechanisms of adrenic acid (ADR), an ω-6 PUFA enriched in inflammatory and oxidative conditions, in red blood cells (RBCs). Purified RBCs were prepared from healthy volunteers and treated with 10–100 μM of ADR for 24 h at 37 °C under various physiological conditions. Eryptotic markers were studied through flow cytometry including Ca²⁺ (Fluo4/AM), loss of volume (forward scatter), phosphatidylserine (PS) exposure (annexin-V-FITC), and oxidative stress (H₂DCFDA). Moreover, hemolytic markers were measured by colorimetric methods, whereas cellular morphology was visualized using a scanning electron microscope. ADR led to significant Ca²⁺ elevation, cell shrinkage and schistocyte formation, PS externalization, hemolysis, and oxidative stress. While guanosine, heparin, and NSC 23766 prevented eryptosis and hemolysis, melatonin, ATP, adenine, and L-NAME only prevented eryptosis. Conversely, mannitol and urea exacerbated eryptosis, whereas caffeine, mannitol, and urea under Ca²⁺ deprivation and membrane potential dissipation aggravated hemolysis. ADR induces erythrocyte membrane injury and eryptosis through Ca²⁺ elevation, oxidative stress, and metabolic exhaustion subject to inhibition by the Rac1 GTPase/NOS/COX pathway. Altogether, these findings present a novel mechanistic link between lipid dysregulation and RBC dysfunction which may improve dietary strategies to prevent and manage CVD. Full article

Proximate composition, lipid classes, and fatty acid profile were comparatively analyzed in different body parts of carp (Cyprinus carpio) cultivated in Madagascar. Higher (p < 0.05) protein values (163.3–200.1 g·kg⁻¹ range) were detected in muscle tissue (epaxial, hypaxial, and tail) than in the liver tissue (118.4 g·kg⁻¹). The average lipid content showed the following decreasing tissue sequence: liver > hypaxial > tail > epaxial. The highest levels (p < 0.05) of phospholipids and sterols were obtained in the epaxial muscle part (94.0 and 24.0 g·kg⁻¹ of lipids, respectively). A high presence of free fatty acids (183.2 g·kg⁻¹ of lipids) was detected in the liver. In all tissues, α-tocopherol provided higher values (p < 0.05) than γ- and δ-tocopherol compounds; among body parts, the liver showed the highest levels (p < 0.05) for all tocopherols. Fatty acid (FA) groups revealed a higher range value (g·100 g⁻¹ of total FAs) for monounsaturated FAs (48.19–52.57) than for saturated FAs (SFAs; 28.50–29.41) and polyunsaturated FAs (PUFAs; 17.96–22.57). The following increasing sequence was observed for ω3-PUFA/ω6-PUFA ratios in body parts: liver < hypaxial < tail < epaxial. All parts of muscle tissue contained higher (p < 0.05) PUFA/SFA values (0.72–0.77) than liver (0.61). Comparison of body parts revealed an inhomogeneous distribution of bioactive compounds. The liver tissue was found a good source of valuable constituents. Full article

Docosahexaenoic acid (DHA) is an essential ω-3 polyunsaturated fatty acid (PUFA) with high nutritional and pharmaceutical value. The marine protist Aurantiochytrium is a promising industrial DHA producer; however, its DHA biosynthesis via the PUFA synthase pathway co-produces ω-6 docosapentaenoic acid (DPA), limiting DHA purity. Here, we introduced an ω-3 desaturase from Phytophthora infestans (Pin-O3D) into Aurantiochytrium sp. SD116. Functional validation in an Escherichia coli system co-expressing the native PUFA synthase confirmed that Pin-O3D converts DPA to DHA, shifting the DHA/DPA ratio from 1:1 to 2:1. Pin-O3D was then integrated into the fatty acid synthase (FAS) locus, simultaneously attenuating FAS activity and enabling heterologous gene expression. The engineered strain ΔFAS-Pin-O3D exhibited significantly (p < 0.0001 in t-test) increased DHA content (55.2% of total fatty acids) and DHA/DPA ratio (5.91) in shake flasks, with no negative impact on biomass or lipid accumulation. Fed-batch fermentation confirmed the scalability of this strategy, achieving a >20% increase in DHA/DPA ratio. This study demonstrates that combining heterologous ω-3 desaturase expression with FAS attenuation is an effective approach for optimizing PUFA profiles in Aurantiochytrium. Full article

Ceramides, sphingolipids produced from fatty acids linked to sphingosine and an amide, are structural elements of cellular membranes and lipoproteins. These molecules also retain biological effects in key cellular pathways such as oxidative stress and inflammation, apoptosis, and fibrosis, with a role in the onset and development of many pathophysiological conditions, including obesity, diabetes, and insulin resistance. Increasing evidence suggests that different nutrients and dietary patterns may affect ceramide levels, both negatively (e.g., fructose and the Western diet), whereas others improve the ceramide profile (e.g., ω-3 PUFAs, resveratrol, vitamin D, and the Mediterranean and the Nordic diets). Thus, ceramide nutritional modulation could represent a simple, additive, and reliable tool to improve metabolic health. This review focused on the role of ceramides in the pathophysiology of diabetes and obesity, as well as their pathogenetic mechanisms of action. Ceramides are increasingly recognized as “dynamic metabolic interfaces” linking nutrition and disease. This review aims to address a critical gap by synthesizing recent evidence on how dietary interventions, in addition to pharmacological approaches, can specifically target the enzymatic pathways involved in ceramide synthesis to enhance metabolic health. Thus, this review offers a concentrated analysis of the response of specific ceramide species, such as Cer16:0 and Cer18:0, to distinct dietary factors. Additionally, it incorporates emerging evidence on the role of gut microbiota in the biotransformation of sphingolipids, thereby adding a contemporary dimension to the established nutritional perspective. Full article

White-backed and Ash-grey cows yielded an average of 6212 kg and 6078 kg of milk per year, with 4.25–4.28% fat and 3.37–3.40% protein, while Holsteins averaged 10,694 kg with 4.47% fat and 3.45% protein. The study aimed to analyse the fatty acid (FA) profile of milk from two local cow breeds, compare them with that of Holstein cows, and evaluate the influence of lactation number, productivity indicators and milk colour. The study was carried out with White-backed (n = 40), Ash-grey (n = 49), and Holstein (n = 51) cows. Based on lactation number, cows were divided into two groups. Composite milk samples from all quarters of each cow were collected. Two additional milk samples were taken: 1st to assess milk colour and the second to determine the fatty acids profile. Productivity data of cows were provided from the Livestock Information System. Statistical analysis included calculating means and standard deviations or standard errors of the mean. One-way and two-way ANOVA (breed and lactation) were used, and Duncan’s test was applied to compare mean values between groups. White-backed cows contained greater proportions of C17:0, C17:1, C18:3 ω3, and C20:0 (p < 0.05), as well as higher total omega-3 and polyunsaturated fatty acid (PUFA) contents. Parity did not have a significant effect on productivity indicators, but parity influenced the FA profile. Milk from 1st-lactation Ash-grey cows showed higher levels of PUFA and omega-6 fatty acids (p < 0.05). Milk from Ash-grey cows has more favourable visual attributes, indicating improved suitability for dairy processing, where colour uniformity is important for technological quality. Full article

Obesity is a persistent public health issue, often resulting in metabolic complications such as insulin resistance (IR). The secretion of pro-inflammatory cytokines from adipose tissue (AT) is increased during obesity, contributing to the impairment of systemic insulin sensitivity. While interventions in animal models have shown that reducing inflammation restores insulin sensitivity, human studies reducing systemic inflammation have produced inconsistent results. We recently demonstrated that three months of high-dose (4 g/daily) ω-3PUFA (fish oil, FO) supplementation improved insulin sensitivity, and decreased systemic and AT inflammation in individuals with obesity (BMI  ≥  30 kg/m²). Given recent studies highlighting the involvement of microRNA (miRNA) in inflammatory cytokine production, we investigated the effect of ω-3PUFA supplementation on AT miRNA expression in this cohort. AT biopsies were collected before and after ω-3PUFA supplementation. miRNA was processed on the Affymetrix miRNA 4.0 GeneChip and analyzed using existing inflammatory gene sets sourced from MSigDB. Unbiased, differentially expressed miRNA analysis identified miR-4498 and miR-5689 as significantly increased after three months of ω-3PUFA supplementation. Real-time PCR confirmed bioinformatic analysis findings. Our study reports the modulation of miRNA in AT, reductions in systemic and AT markers of inflammation, and the improvement of IR post ω-3PUFA supplementation. Further research is needed to elucidate the link between miR-4498, miR-5689, and whole-body insulin sensitivity. Full article

Impaired blood–brain barrier (BBB) integrity is a common hallmark of neurological disorders associated with neuroinflammation, neurodegeneration and aging. The function of the BBB relies heavily on the interaction between astrocytes and endothelial cells, the most closely connected elements of the neurovascular unit. Under inflammatory conditions, astrocytes can undergo a range of metabolic changes, becoming pro-inflammatory and harmful to endothelial cells. Upon activation, astrocytes secrete a plethora of inflammatory mediators that severely disrupt the barrier function of the BBB. ω-3 polyunsaturated fatty acids (PUFAs), mainly docosahexaenoic and eicosapentaenoic acids, exhibit protective anti-inflammatory and antioxidant effects demonstrated in various neurological disorders. This review focused on the role of ω-3 PUFAs and their oxidative derivatives, specialized pro-resolving mediators, in preserving the BBB’s integrity via suppression of astrocytes’ activation or even promotion of their transition from an A1 to an A2 phenotype. We considered mainstream mechanisms of the anti-inflammatory and antioxidant effects of ω-3 PUFAs on reactive astrocytes, such as stimulation of the Nrf2/ARE and Wnt/β-catenin signaling pathways, inhibition of NF-κB/matrix metalloproteinase activity and the JAK/STAT3 signaling axis, as well as the contribution of ω-3 PUFA-activated GPCRs and PPAR transcriptional factors, particularly regarding the role of these mechanisms in preserving the BBB’s integrity. Full article

Seafood processing generates large volumes of by-products that are often underutilized despite their potential as sources of high-value bioactive lipids. In this study, a hybrid process integrating microwave (MW) pretreatment with Soxhlet (SOX) extraction was developed and optimized to intensify the recovery of astaxanthin (ASX)- and ω-3 PUFA-rich oil from green tiger shrimp (Penaeus semisulcatus) residues. Response surface methodology (RSM) comprising 22 experimental runs was applied to optimize key MW process variables, including power (100–400 W) and irradiation time (30–90 s). Both factors significantly influenced oil yield, with optimal operating conditions identified at 400 W and 75 s. MW pretreatment promoted structural disruption of shrimp shells, as confirmed by scanning electron microscopy, thereby enhancing solvent penetration and mass transfer. Solvent selection further affected extraction performance: hexane:isopropanol (1:1, v/v) achieved the highest oil yield (3.86 g/100 g dry weight), while hexane:acetone produced extracts with the highest ASX concentration (1032.24 µg/g oil), ω-3 PUFA content (29.85%), and antioxidant activity (93.30% DPPH scavenging). Colorimetric analysis supported these results, with increased redness (a* = 18.12) correlating with ASX enrichment. Overall, this integrated MW-SOX process represents an effective process-intensification strategy for sustainable shrimp waste valorization and production of bioactive lipid fractions. Full article

Background/Objectives: The retina is enriched in polyunsaturated fatty acids (PUFAs) which are indispensable for normal vision, and recent clinical studies have shown that dietary supplementation of ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) can provide a protective role against retinopathy of prematurity (ROP). Our study aims to understand the mechanisms by which altering ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) in the eye can protect against pathologic retinal neovascularization (NV). Methods: We interrogated the effects of endogenous ω-3-PUFA enrichment using transgenic fat-1 mice which convert ω-6-PUFAs to ω-3-PUFAs in the oxygen-induced retinopathy (OIR) murine model. In the OIR model, mice are exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air (RA). We used a combination of immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling by UHPLC-MS/MS in P17 mouse retinas to identify mechanisms underlying the protective effect against NV seen in fat-1 mice exposed to OIR. Results:Fat-1 OIR mice were protected against the development of retinopathy, demonstrating 15.1% less vaso-obliteration (75.5% relative reduction) after OIR and a 6.1% reduction in neovascularization (71.8% relative reduction) at P17 (p < 0.0001 for both). We found a dampened transcriptional response to OIR in the retina of fat-1 mice as compared to WT mouse retinas (198 vs. 782 genes, adjusted p-value < 0.01). Pathway analyses confirmed these findings, with significant OIR-induced transcriptional shifts in angiogenesis (adjusted p-value < 10⁻²⁷), inflammation (adjusted p-value < 10⁻²⁵), and microglial activation pathways (adjusted p-value < 10⁻⁹) in WT mouse retina that were not observed in fat-1 mice. Enrichment scores obtained through the integration of our bulk transcriptomics data with cell-resolved retina data indicate that the protective phenotype observed in fat-1 mice could be associated with intrinsic differences in microglia cell subtypes between WT and fat-1 mice. In situ, WT OIR mice demonstrated an increase in Iba1+ microglia compared to WT RA mice, whereas fat-1 OIR mice showed no difference when compared to fat-1 RA mice. Three ARA-derived oxylipins, 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin D2 (PGD2), and thromboxane B2 (TXB2) demonstrated a pattern of upregulation in WT OIR compared to WT RA, but no upregulation in fat-1 OIR mice compared to fat-1 RA. Two EPA-derived specialized pro-resolving mediators and two LA-derived oxylipins were also differentially expressed. Conclusions: These findings show that a lower ω-6:ω-3 protects against neovascularization and is associated with attenuation of hyperoxia-induced microglial recruitment and activation, as well as inflammation and angiogenic signaling. Full article

Background/Objectives: Circulating inflammatory cytokines and tissue sensitivity are both elevated following heat stress-induced intrauterine growth restriction (IUGR). Cytokines disrupt myoblast function and muscle growth, and thus we hypothesized that suppressing inflammatory tone in IUGR-born lambs by supplementing anti-inflammatory nutraceuticals would improve early postnatal growth. Methods: IUGR lambs produced by maternal heat stress were supplemented daily with 42 mg/kg oral omega-3 polyunsaturated fatty acid (ω-3 PUFA) Ca²⁺ salts or placebo from birth to 28 days of age. Results: By day 28, the 21% lighter bodyweights for IUGR lambs were fully resolved by ω-3 PUFA due to the complete recovery of average daily gain. Subcutaneous fat deposition and visceral organ growth were modestly diminished in IUGR-born lambs, but skeletal muscle mass was more markedly restricted. This coincided with 63% less muscle AdipoR2 but 27% greater circulating adiponectin. ω-3 PUFA reduced or eliminated deficits in subcutaneous fat, visceral organs, and five of the six individual muscles assessed, which corresponded with rescue of myoblast populations and AdipoR2 content. In turn, asymmetric growth restriction was resolved at one month of age. Conclusions: These findings show that targeting heightened inflammatory tone during the neonatal period in IUGR-born offspring can recover early growth in skeletal muscle and other soft tissues. Full article

Background/Objectives: Chronic heat stress impairs lipid mobilization from adipocytes, which reduces substrate availability for muscle metabolism. Systemic inflammation is a key facilitative response to heat stress, and we sought to determine if mitigating inflammation in heat-stressed wether lambs would improve lipid flux. Methods: Two cohorts of commercial feedlot lambs were heat stressed for 30 days. In study 1, heat-stressed lambs received dexamethasone injections every 3 days, fish oil capsules twice daily, or no intervention. In study 2, heat-stressed lambs received daily boluses of ω-3 polyunsaturated fatty acid Ca²⁺ salts (ω-3 PUFA) or no intervention. Results: In both studies, heat stress reduced ex vivo epinephrine-stimulated free fatty acid and glycerol mobilization from visceral adipose tissue. These deficits were partially resolved by fish oil and fully resolved by ω-3 PUFA. In study 1, fish oil recovered heat stress-induced deficits in circulating triglycerides and HDL-cholesterol but not in circulating free fatty acids. Fish oil and dexamethasone resolved the increase in muscle PPARα, indicating less lipid utilization for metabolism. In study 2, ω-3 PUFA resolved heat stress-induced deficits in muscle CD36 and PPARγ, indicating improved lipid uptake capacity. However, interventions did not resolve reduced intramuscular lipid content in either study. Conclusions: We conclude that inflammation was a primary facilitator of impaired lipid mobilization in heat-stressed lambs but was not the sole driver of lipid dysregulation. Nevertheless, targeting inflammation was a beneficial strategy for improving lipid flux during chronic heat stress. Full article

Currently, ω-3 polyunsaturated fatty acids (PUFAs), which have become popular as dietary supplements, are limited by a shortage in supply. Thus, finding safe, effective alternatives is crucial. Echium seed oil (ESO), rich in α-linolenic acid (ALA, 18:3ω-3) and stearidonic acid (SDA, 18:4ω-3), surpasses many other botanical seed oils. In this study, a pseudotargeted approach was applied to characterize the lipidomic profile of two unexplored Echium species from the Mediterranean region. Our findings established Echium glomeratum as a rich source of ω-3 fatty acids (FAs), exceeding many other species in both quality and quantity. E. glomeratum possesses different FAs and triglyceride (TG) profiles compared to E. judaeum, with the ω-3:ω-6 ratio being 3.5 and 1.3, respectively. This corresponds to higher quantities of ALA (45.50%) and SDA (12.59%) in E. glomeratum. Triglycerides (TGs) comprise 93% of the total lipid content in ESO. This study also profiled the most abundant TGs (50–60 carbons) from both species through comprehensive assignment of the olefination patterns. The E. glomeratum oil profile, containing a higher ω-3 PUFA concentration, was further screened for cytotoxic and antioxidant activities. Our preliminary results demonstrated that E. glomeratum ESO may significantly suppress colon cancer cell growth. Full article

This study investigated the effects of different dietary flaxseed inclusion levels (0, 2, 4, 6, 8, and 10%) on the fatty acid composition, plasma biochemical parameters, and meat quality of Beijing-you chickens. A total of 960 6-week-old birds were randomly assigned to six dietary treatments in a completely randomized design, with eight replicates per treatment. Dietary flaxseed supplementation significantly decreased plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) concentrations (p < 0.05), while significantly increasing high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05). Meat quality was also improved, as evidenced by reduced drip loss (p < 0.05). Moreover, gas chromatography analysis revealed that increasing dietary flaxseed levels markedly elevated the concentrations of total ω-3 polyunsaturated fatty acids (ω-3 PUFAs) in both breast and leg muscles (p < 0.05), accompanied by a significant reduction in the ω-6/ω-3 ratio (p < 0.05). Dietary flaxseed supplementation did not significantly affect the docosahexaenoic acid (DHA) content in pectoral muscle (p > 0.05), with the highest value observed at the 6% inclusion level. In conclusion, dietary flaxseed supplementation effectively enriches ω-3 PUFAs in chicken meat while simultaneously enhancing metabolic health indicators and improving meat quality traits. Full article

Background/Objectives: Watermelon (Citrullus lanatus) processing generates substantial quantities of rind, seeds, and residual pulp that are typically discarded despite being rich in polyunsaturated fatty acids, polar lipids, carotenoids, and phenolic compounds. These amphiphilic bioactives are increasingly recognized for their roles in modulating oxidative stress, inflammation, and platelet activation; however, the lipid fraction of watermelon by-products remains insufficiently characterized. This study examined organic watermelon juice and its by-products to isolate, characterize, and evaluate extracts enriched in amphiphilic and lipophilic bioactives, with emphasis on their in vitro antioxidant, anti-inflammatory, and antithrombotic properties. Methods: total lipids were extracted using a modified Bligh–Dyer method and fractionated into total amphiphilic compounds (TAC) and total lipophilic compounds (TLC) via counter-current distribution. Phenolic and carotenoid levels were quantified, and antioxidant capacity was assessed using DPPH, ABTS, and FRAP assays. Anti-platelet and anti-inflammatory activities were evaluated against ADP- and PAF-induced platelet aggregation. Structural characterization of polar lipids was performed using ATR–FTIR, and LC–MS was used to determine fatty acid composition and phospholipid structures. Results and Discussion: Carotenoids were primarily concentrated in the TLC fractions with high ABTS values for antioxidant activity, while phenolics mostly in the juice, the TACs of which showed the strongest total antioxidant capacity based on DPPH. TAC fractions of both samples showed also higher FRAP values of antioxidant activity, likely due to greater phenolic content. TAC extracts also exhibited notable inhibition of PAF- and ADP-induced platelet aggregation, associated with their enriched ω-3 PUFA profiles and favorable ω-6/ω-3 ratios based on their LC-MS profiles. Conclusions: Overall, watermelon products (juice) and by-products represent a valuable and sustainable source of amphiphilic bioactives with significant antioxidant, anti-inflammatory, and anti-platelet potential, supporting their future use in functional foods, nutraceuticals, and cosmetic applications. Full article

Purpose: To investigate associations between lipid oxidation biomarkers (oxylipins), antioxidant micronutrients, lipoprotein particles, and apolipoproteins in multiple sclerosis (MS). Methods: Blood and neurological assessments were collected from 30 healthy controls, 68 relapsing remitting MS subjects, and 37 progressive MS subjects. Hydroxy (H) and hydroperoxy lipid peroxidation products of the polyunsaturated fatty acids (PUFAs) arachidonic (20:4, ω-6), linoleic (octadecadienoic acid or ODE, 18:2, ω-6), eicosapentaenoic (20:5, ω-3), and α-linolenic (18:3, ω-3) acids were measured using liquid chromatography–mass spectrometry. Antioxidant micronutrients, including β-cryptoxanthin and lutein/zeaxanthin, were quantified by high-performance liquid chromatography. Lipoprotein and metabolite profiles were obtained using nuclear magnetic resonance spectroscopy. Regression models were adjusted for age, sex, body mass index, and disease status. Results: The 9-hydroxy octadecadienoic acid to 13-hydroxy octadecadienoic acid ratio (9-HODE/13-HODE ratio), which reflects autoxidative versus enzymatic oxidation, was associated with MS status (p = 0.002) and disability on the Expanded Disability Status Scale (p = 0.004). Lutein/zeaxanthin (p = 0.023) and β-cryptoxanthin (p = 0.028) were negatively associated with the 9-HODE/13-HODE ratio. Apolipoprotein-CII, a marker of liver-X-receptor (LXR) signaling, was associated with 9-HODE/13-HODE ratio and other oxylipins. Octadecadienoic fatty acid-derived oxylipins were negatively associated with LC3A, a mitophagy marker, and positively correlated with 7-ketocholesterol, a cholesterol autoxidation product. Conclusions: Autoxidation of PUFAs is associated with greater disability in MS. Higher β-cryptoxanthin and lutein/zeaxanthin were associated with reduced auto-oxidation. Lipid peroxidation shows associations with LXR signaling, mitophagy, inflammation, and cholesterol autoxidation. Full article