Search Results (51)

Background/Objectives: Neuroinflammation, a hallmark of Alzheimer’s disease (AD), is characterized by elevated levels of inflammatory signaling molecules, including cytokines and eicosanoids, as well as increased microglial reactivity, and is augmented by gut microbiota dysbiosis via the gut–brain axis. We conducted a pilot experiment to elucidate the anti-inflammatory effects of dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) eicosapentaenoic acid (EPA) on the gut microbiota and neuroinflammation. Methods: Female APP/PS1 mice (TG) and non-transgenic littermates (WT), 13–14 months old, were fed a diet supplemented with 0.3% EPA or control chow for 3 weeks. The gut microbiota composition, hippocampal and plasma eicosanoids levels, platelet activation, and microglial phagocytosis, as well as the brain and retinal genes and protein expression, were analyzed. Results: EPA supplementation decreased the percentage of Bacteroidetes and increased bacteria of the phylum Firmicutes in APP/PS1 and WT mice. Inflammatory lipid mediators were elevated in the hippocampus of the TG mice, accompanied by a reduction in the endocannabinoid docosahexaenoyl ethanolamide (DHEA). Dietary EPA did not affect hippocampal lipid mediators, but reduced the levels of arachidonic-derived 5-HETE and N-arachidonoylethanolamine (AEA) in WT plasma. Moreover, EPA supplementation decreased major histocompatibility complex class II (MHCII) gene expression in the retina in both genotypes, and MHCII+ cells in the hippocampus of TG mice. Conclusions: This pilot study showed that short-term EPA supplementation shaped the gut microbiota by increasing butyrate-producing bacteria of the Firmicutes phylum and decreasing Gram-negative LPS-producing bacteria of the Bacteroidetes phylum, and downregulated the inflammatory microglial marker MHCII in two distinct regions of the central nervous system (CNS). Further investigation is needed to determine whether EPA-mediated effects on the microbiome and microglial MHCII have beneficial long-term effects on AD pathology and cognition. Full article

This study aimed to assess the effects of a diet containing 20.8 mg FB1 + FB2/kg over four and nine days on oxylipin (OL) profiles in the liver and brain of chickens. A total of 96 OLs, derived from seven polyunsaturated fatty acids (PUFAs) via the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (P450), and non-enzymatic pathways, were measured using HPLC-MS/MS. In the liver, a significant increase in epoxide P450-derived OLs was detected by day 4, with smaller but notable increases in COX- and LOX-derived OLs by day 9. These alterations were independent of whether the parent PUFA was ω6 or ω3. However, OLs derived from 18-carbon (C18) PUFAs, such as linoleic acid and alpha-linolenic acid, showed greater increases compared to those derived from C20 or C22 PUFAs. The diol/epoxide ratios in the liver decreased at four and nine days, suggesting that fumonisins did not induce an inflammatory response. In the brain, at four days, the most discriminative OLs were derived from ω3-PUFAs, including docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid, via the LOX pathway. By nine days, several OLs derived from arachidonic acid, spanning all enzymatic pathways, became discriminative. In general, the diol/epoxide ratios in the brain were decreased at 4 days and then returned to the initial levels. Taken together, these results show strong effects of fumonisins on OLs in the liver and brain that are both specific and distinct. Full article

Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions. Methods: The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a “healthy” control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats. Results: We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes CYP1B1, CYP2J3, and CYP1A1 and in the time course of expression changes with age. Conclusions: We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats. Full article

“Bubblegum” acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD). To explore ACSBG1’s function and potential as a therapeutic target in XALD, we created an ACSBG1 knockout (Acsbg1^−/−) mouse and examined the effects on brain FA metabolism during development. Phenotypically, Acsbg1^−/− mice resembled wild type (w.t.) mice. ACSBG1 expression was found mainly in tissue affected pathologically in XALD, namely the brain, adrenal gland and testis. ACSBG1 depletion did not significantly reduce the total ACS enzyme activity in these tissue types. In adult mouse brain, ACSBG1 expression was highest in the cerebellum; the low levels detected during the first week of life dramatically increased thereafter. Unexpectedly, lower, rather than higher, saturated VLCFA levels were found in cerebella from Acsbg1^−/− vs. w.t. mice, especially after one week of age. Developmental changes in monounsaturated ω9 FA and polyunsaturated ω3 FA levels also differed between w.t. and Acsbg1^−/− mice. ACSBG1 deficiency impacted the developmental expression of several cerebellar FA metabolism enzymes, including those required for the synthesis of ω3 polyunsaturated FA, precursors of bioactive signaling molecules like eicosanoids and docosanoids. These changes in membrane lipid FA composition likely affect membrane fluidity and may thus influence the body’s response to inflammation. We conclude that, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD, decreasing its potential as a therapeutic target. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and/or docosanoids should be further investigated. Full article

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs, n-3 PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), are essential polyunsaturated fats primarily obtained from fatty fish and plant-based sources. Compelling evidence from preclinical and epidemiological studies consistently suggests beneficial effects of ω-3 PUFAs on bone health and healthy aging processes. However, clinical trials have yielded mixed results, with some failing to replicate these benefits seen in preclinical models. This contraindication is mainly due to challenges such as low bioavailability, potential adverse effects with higher doses, and susceptibility to oxidation of ω-3 fatty acids, hindering their clinical effectiveness. This review comprehensively discusses recent findings from a clinical perspective, along with preclinical and epidemiological studies, emphasizing the role of ω-3 PUFAs in promoting bone health and supporting healthy aging. Additionally, it explores strategies to improve ω-3 PUFA efficacy, including nanoparticle encapsulation and incorporation of specialized pro-resolving mediators (SPM) derived from DHA and EPA, to mitigate oxidation and enhance solubility, thereby improving therapeutic potential. By consolidating evidence from various studies, this review underscores current insights and future directions in leveraging ω-3 PUFAs for therapeutic applications. Full article

Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients. Full article

The global focus on incorporating natural ingredients into the diet for health improvement encompasses ω-3 polyunsaturated fatty acids (PUFAs) derived from plant sources, such as flaxseed oil. ω-3 PUFAs are susceptible to oxidation, but oil-in-water (O/W) emulsions can serve to protect PUFAs from this phenomenon. This study aimed to create O/W emulsions using flaxseed oil and either soy lecithin or Quillaja saponins, thickened with modified starch, while assessing their physical properties (oil droplet size, ζ-potential, and rheology) and physical stability. Emulsions with different oil concentrations (25% and 30% w/w) and oil-to-surfactant ratio (5:1 and 10:1) were fabricated using high-pressure homogenization (800 bar, five cycles). Moreover, emulsions were thickened with modified starch and their rheological properties were measured. The physical stability of all emulsions was assessed over a 7-day storage period using the TSI (Turbiscan Stability Index). Saponin-stabilized emulsions exhibited smaller droplet diameters (0.11–0.19 µm) compared to lecithin (0.40–1.30 µm), and an increase in surfactant concentration led to a reduction in droplet diameter. Both surfactants generated droplets with a high negative charge (−63 to −72 mV), but lecithin-stabilized emulsions showed greater negative charge, resulting in more intense electrostatic repulsion. Saponin-stabilized emulsions showed higher apparent viscosity (3.9–11.6 mPa·s) when compared to lecithin-stabilized ones (1.19–4.36 mPa·s). The addition of starch significantly increased the apparent viscosity of saponin-stabilized emulsions, rising from 11.6 mPa s to 2117 mPa s. Emulsions stabilized by saponin exhibited higher stability than those stabilized by lecithin. This study confirms that plant-based ingredients, particularly saponins and lecithin, effectively produce stable O/W emulsions with flaxseed oil, offering opportunities for creating natural ingredient-based food emulsions. Full article

Omega-3 long-chain (≥C₂₀) polyunsaturated fatty acids (ω3 LC-PUFA) play a critical physiological role in health and are nutritionally important for both humans and animals. The abundance of marine-derived resources of the health-benefitting ω3 LC-PUFA is either static or in some cases declining. This review focuses on the development and deregulation of novel oilseed crops producing ω3 LC-PUFA and their market applications. Genetic engineering of ω3 LC-PUFA into sustainable oilseed crops involving multiple-gene pathways to reach fish oil-like levels of these key nutrients has been extremely challenging. After two decades of collaborative effort, oilseed crops containing fish oil-levels of ω3 LC-PUFA and importantly also containing a high ω3/ω6 ratio have been developed. Deregulation of genetically engineered crops with such novel nutritional traits is also challenging and more trait-based regulations should be adopted. Some ω3 LC-PUFA-producing oilseed crops have been approved for large-scale cultivation, and for applications into feed and food. These genetically engineered oilseed crops can and will help meet the increasing market demand for aquaculture and human nutrition. These new oil seed sources of ω3 LC-PUFA offer a sustainable, safe, cost-effective, and scalable land-based solution, which can have critical and positive health, economic, and environmental impacts. Full article

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are “essential” fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of “residual” cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented “pleiotropic” actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes. Full article

Cottonseed is the second major product of cotton (Gossypium spp.) crops after fiber. Thus, the characterization and valorization of cottonseed are important parts of cotton utilization research. In this work, the nonpolar and polar fractions of glanded (Gd) cottonseed were sequentially extracted by 100% hexane and 80% ethanol aqueous solutions and subjected to ¹³C and ¹H nuclear magnetic resonance (NMR) spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), respectively. The nonpolar (crude oil) extracts showed the characteristic NMR peak features of edible plant oils with the absence of ω-3 linolenic acid. Quantitative analysis revealed the percentage of polyunsaturated, monounsaturated, and saturated fatty acids as 48.7%, 16.9%, and 34.4%, respectively. Both general unsaturated fatty acid features and some specific olefinic compounds (e.g., oleic, linolenic, and gondonic acids) were found in the nonpolar fraction. In the polar extracts, FT-ICR MS detected 1673 formulas, with approximately 1/3 being potential phenolic compounds. Both the total and phenolic formulas fell mainly in the categories of lipid, peptide-like, carbohydrate, and lignin. A literature search and comparison further identifies some of these formulas as potential bioactive compounds. For example, one compound [2,5-dihydroxy-N′-(2,3,4-trihydroxybenzylidene) benzohydrazide] identified in the polar extracts is likely responsible for the anticancer function observed when used on human breast cancer cell lines. The chemical profile of the polar extracts provides a formulary for the exploration of bioactive component candidates derived from cottonseed for nutritive, health, and medical applications. Full article

Aside from their bioremediation roles, little is known about the food and feed value of earthworms. In this study, a comprehensive evaluation of the nutritional composition (proximate analysis and profiles of fatty acids and minerals) and techno-functional properties (foaming and emulsion stability and capacity) of earthworm (Eisenia andrei, sourced in New Zealand) powder (EAP) were investigated. Lipid nutritional indices, ω6/ω3, atherogenicity index, thrombogenicity index, hypocholesterolemic/hypercholesterolemic acid ratio, and health-promoting index of EAP lipids are also reported. The protein, fat, and carbohydrate contents of EAP were found to be 53.75%, 19.30%, and 23.26% DW, respectively. The mineral profile obtained for the EAP consisted of 11 essential minerals, 23 non-essential minerals, and 4 heavy metals. The most abundant essential minerals were potassium (8220 mg·kg⁻¹ DW), phosphorus (8220 mg·kg⁻¹ DW), magnesium (744.7 mg·kg⁻¹ DW), calcium (2396.7 mg·kg⁻¹ DW), iron (244.7 mg·kg⁻¹ DW), and manganese (25.6 mg·kg⁻¹ DW). Toxic metals such as vanadium (0.2 mg·kg⁻¹ DW), lead (0.2 mg·kg⁻¹ DW), cadmium (2.2 mg·kg⁻¹ DW), and arsenic (2.3 mg·kg⁻¹ DW) were found in EAP, which pose safety considerations. Lauric acid (20.3% FA), myristoleic acid (11.20% FA), and linoleic acid (7.96% FA) were the most abundant saturated, monounsaturated, and polyunsaturated fatty acids, respectively. The lipid nutritional indices, such as IT and ω-6/ω-3, of E. andrei were within limits considered to enhance human health. A protein extract derived from EAP (EAPPE), obtained by alkaline solubilisation and pH precipitation, exhibited an isoelectric pH of ~5. The total essential amino acid content and essential amino acid index of EAPPE were 373.3 mg·g⁻¹ and 1.36 mg·g⁻¹ protein, respectively. Techno-functional analysis of EAPPE indicated a high foaming capacity (83.3%) and emulsion stability (88.8% after 60 min). Heat coagulation of EAPPE was greater at pH 7.0 (12.6%) compared with pH 5.0 (4.83%), corroborating the pH-solubility profile and relatively high surface hydrophobicity (1061.0). These findings demonstrate the potential of EAP and EAPPE as nutrient-rich and functional ingredients suitable as alternative food and feed material. The presence of heavy metals, however, should be carefully considered. Full article

Grain amaranth (Amaranthus spp.) is an emerging crop rich in proteins and other valuable nutrients. It was domesticated twice, in Mexico and Peru. Although global trade is dominated by Mexican species of amaranth, Peruvian amaranth (A. caudatus, kiwicha) has remained neglected, although it harbours valuable traits. In the current study, we investigate the accumulation of polyunsaturated fatty acids, comparing four genotypes of A. caudatus with K432, a commercial variety deriving from the Mexican species A. hypochondriacus under the temperate environment of Southwest Germany. We show that the A. caudatus genotypes flowered later (only in late autumn), such that they were taller as compared to the Mexican hybrid but yielded fewer grains. The oil of kiwicha showed a significantly higher content of unsaturated fatty acids, especially of linoleic acid and α-linolenic acid compared to early flowering genotype K432. To gain insight into the molecular mechanisms behind these differences, we sequenced the genomes of the A. hypochondriacus × hybridus variety K432 and the Peruvian kiwicha genotype 8300 and identified the homologues for genes involved in the ω3 fatty-acid pathway and concurrent oxylipin metabolism, as well as of key factors for jasmonate signalling and cold acclimation. We followed the expression of these transcripts over three stages of seed development in all five genotypes. We find that transcripts for Δ6 desaturases are elevated in kiwicha, whereas in the Mexican hybrid, the concurrent lipoxygenase is more active, which is followed by the activation of jasmonate biosynthesis and signalling. The early accumulation of transcripts involved in cold-stress signalling reports that the Mexican hybrid experiences cold stress already early in autumn, whereas the kiwicha genotypes do not display indications for cold stress, except for the very final phase, when there were already freezing temperatures. We interpret the higher content of unsaturated fatty acids in the context of the different climatic conditions shaping domestication (tropical conditions in the case of Mexican amaranth, sharp cold snaps in the case of kiwicha) and suggest that kiwicha oil has high potential as functional food which can be developed further by tailoring genetic backgrounds, agricultural practice, and processing. Full article

Oils are an essential part of the human diet and are primarily derived from plant (or sometimes fish) sources. Several of them exhibit anti-inflammatory properties. Specific diets, such as Mediterranean diet, that are high in ω-3 polyunsaturated fatty acids (PUFAs) and ω-9 monounsaturated fatty acids (MUFAs) have even been shown to exert an overall positive impact on human health. One of the most widely used supplements in the developed world is fish oil, which contains high amounts of PUFAs docosahexaenoic and eicosapentaenoic acid. This review is focused on the natural sources of various polyunsaturated and monounsaturated fatty acids in the human diet, and their role as precursor molecules in immune signaling pathways. Consideration is also given to their role in CNS immunity. Recent findings from clinical trials utilizing various fatty acids or diets high in specific fatty acids are reviewed, along with the mechanisms through which fatty acids exert their anti-inflammatory properties. An overall understanding of diversity of polyunsaturated fatty acids and their role in several molecular signaling pathways is useful in formulating diets that reduce inflammation and increase longevity. Full article

ω-3 Polyunsaturated fatty acids (PUFAs) have been found to exert many actions, including neuroprotective effects. In this regard, the exact molecular mechanisms are not well understood. Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. Emerging evidence supports the hypothesis that PD is the result of complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction, and other cellular processes, such as DNA methylation. In this context, BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) have a pivotal role because they are both involved in neuron differentiation, survival, and synaptogenesis. In this study, we aimed to elucidate the potential role of two PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their effects on BDNF and GDNF expression in the SH-SY5Y cell line. Cell viability was determined using the MTT assay, and flow cytometry analysis was used to verify the level of apoptosis. Transmission electron microscopy was performed to observe the cell ultrastructure and mitochondria morphology. BDNF and GDNF protein levels and mRNA were assayed by Western blotting and RT-PCR, respectively. Finally, methylated and hydroxymethylated DNA immunoprecipitation were performed in the BDNF and GDNF promoter regions. EPA, but not DHA, is able (i) to reduce the neurotoxic effect of neurotoxin 6-hydroxydopamine (6-OHDA) in vitro, (ii) to re-establish mitochondrial function, and (iii) to increase BNDF and GDNF expression via epigenetic mechanisms. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω₃) fatty acids are polyunsaturated fatty acids (PUFAs) that are largely obtained from diet and have been speculated to decrease the inflammatory response that is involved in IBD; however, the causality of this association has not been established. A two-sample Mendelian randomization (MR) was used to assess genetic associations between 249 circulating metabolites measured in the UK Biobank as exposures and IBD as the outcome. The genome-wide association study summary level data for metabolite measurements and IBD were derived from large European ancestry cohorts. We observed ω₃ fatty acids as a significant protective association with IBD, with multiple modes of MR evidence replicated in three IBD summary genetic datasets. The instrumental variables that were involved in the causal association of ω₃ fatty acids with IBD highlighted an intronic SNP, rs174564, in FADS2, a protein engaged in the first step of alpha-linolenic acid desaturation leading to anti-inflammatory EPA and thence DHA production. A low ratio of ω₃ to ω₆ fatty acids was observed to be a causal risk factor, particularly for Crohn’s disease. ω₃ fatty acid supplementation may provide anti-inflammatory responses that are required to attenuate inflammation that is involved in IBD. Full article