Search Results (47)

Background/Objectives: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. Methods: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD–LHM) and those with VD deficiency and high HM exposure (VDD–HHM). Results: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651–0.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. Conclusions: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions. Full article

Background: Sufficient choline supply is essential for tissue functions via phosphatidylcholine and sphingomyelin within membranes and secretions like bile, lipoproteins and surfactant, and in one-carbon metabolism via betaine. Choline requirements are linked to age and genetics, folate and cobalamin via betaine, and arachidonic (ARA) and docosahexaenoic (DHA) acid transport via the phosphatidylcholine moiety of lipoproteins. Groups at risk of choline deficiency include preterm infants, children with cystic fibrosis (CF) and patients dependent on parenteral nutrition. Fortifiers, formula and supplements may differently impact their choline supply. Objective: To evaluate added amounts of choline, folate, cobalamin, ARA and DHA in fortifiers, supplements and formula used in pediatric care from product files. Methods: Nutrient contents from commonly used products, categorized by age and patient groups, were obtained from public sources. Data are shown as medians and interquartile ranges. Results: 105 nutritional products including fortifiers, formula and products for special indications were analyzed. Choline concentrations were comparable in preterm and term infant formulas (≤6 months) (31.9 [27.6–33.3] vs. 33.3 [30.8–35.2] mg/100 kcal). Products for toddlers, and patients with CF, kidney or Crohn’s disease showed Choline levels from 0 to 39 mg/100 kcal. Several products contain milk components and lecithin-based emulsifiers potentially increasing choline content beyond indicated amounts. Conclusions: Choline addition is standardized in formula for term and preterm infants up to 6 months, but not in other products. Choline content may be higher in several products due to non-declared sources. The potential impact of insufficient choline supply in patients at risk for choline deficiency suggests the need for biochemical analysis of products. Full article

Freshwater fish species play an important role in global aquaculture. Currently, sturgeon, carp, and tilapia are at the forefront of this industry. However, as human populations continue to grow, the demand for new sources of animal protein increases, making the use of other freshwater species in aquaculture essential. The pikeperch (Sander lucioperca) is one of the most promising fish species for European aquaculture, but its usage has been hindered by a lack of effective larval-rearing protocols. Most studies focus on using cultured or nutrient-rich zooplankton for larval cultivation, while natural zooplankton from the local environment are rarely used. In this study, we aim to investigate the nutritional requirements of pikeperch larvae by describing the taxonomic diversity and biochemical composition of zooplankton collected from a natural oligotrophic lake in Northwest Russia. The chemical composition of zooplankton is characterized by a high protein content (up to 70% of dry matter), a moderate lipid content (up to 25%), and a deficiency of certain fatty acids and amino acids. Specifically, there is a low concentration of docosahexaenoic acid and methionine. The dry matter content in the zooplankton averages 10%, with nitrogen-free extracts accounting for 4% and ash making up 4%. These biochemical parameters meet the nutritional requirements of freshwater pikeperch larvae, with the notable exception of the lower levels of DHA and methionine, which are typically characteristic of freshwater zooplankton. This information sheds light on the nutritional requirements of pikeperch larvae and the development of more efficient rearing methods. Full article

Background/Objective: Zinc deficiency is common worldwide and has been linked to reduced growth and immune function, increased risk of and slower recovery from infections, and increased risk of non-communicable diseases. To address the issue, zinc biofortification of wheat has been proposed as a sustainable approach to increase dietary zinc intake in countries like Pakistan, where zinc deficiency rates are high and wheat is the primary staple crop. Since plasma zinc concentration (PZC) does not reliably respond to small changes in zinc intake, biomarkers sensitive to small changes in zinc intake achievable though biofortification are needed. Activity indices for zinc-dependent metabolic steps of desaturation and elongation of omega-6 fatty acids (FAs) have been proposed as sensitive zinc biomarkers. Oxylipin metabolites of polyunsaturated FAs may also respond to changes in zinc intake and further mediate metabolic response to oxidative stress. The objective of the current study was to assess the effects of consuming zinc-biofortified wheat flour on plasma markers of fatty acid (FA) metabolism in females aged 10–16 years. Methods: A nested secondary analysis was conducted in samples from a double-blind, cluster-randomized controlled trial conducted in rural Pakistan, whereparticipants (n = 517) consumed either zinc-biofortified wheat flour or control flour for 25 weeks. Total plasma FAs and oxylipins were measured by liquid chromatography tandem mass spectrometry (LC–MS/MS). Activity indices were estimated from the ratios of product to precursor FAs. Results: Except for docosahexaenoic acid (DHA, p < 0.05), no significant intervention effect was observed on plasma FAs and FA activity index endpoints. Zinc-biofortified wheat intake reduced pro-inflammatory oxylipins and biomarkers of oxidative stress, 5-HETE (p < 0.05), 9-HETE (p < 0.05), 11-HETE (p < 0.05), and 15-HETE (p < 0.05), compared with the control. However, after adjustment for multiple comparisons, none of the intervention effects remained significant. Conclusions: Further study of the responsiveness and specificity of plasma oxylipins to changes in zinc intake is warranted. Full article

Enhancing microalgal growth and bioactive compound production is becoming a duty for improving photosynthetic microorganisms. In this study, the growth, carotenoid, and fatty acid profiles of Conticribra weissflogii were studied under four different silicate concentrations and silicate-deficient conditions in an f/2 medium with continuous aeration, light intensity (30 ± 2 µmol m⁻² s⁻¹), salinity (25 ± 2‰), pH (8), and temperature (25 ± 2 °C). At the end of the experiment, we observed that a silicate concentration of 120 mg L⁻¹ produced the maximum biomass dry weight (0.86 g L⁻¹), carotenoid content (1.63 µg mL⁻¹), and fucoxanthin content (1.23 mg g⁻¹) in C. weissflogii. The eicosapentaenoic acid (EPA) (11,354.37 µg g⁻¹), docosahexaenoic acid (DHA) (2516.16 µg g⁻¹), gamma-linolenic acid (C18:3n6) (533.51 µg g⁻¹), and arachidonic acid (C20:4n6) (1261.83 µg g⁻¹) contents were significantly higher at Si 120 mg L⁻¹. The results further showed the maximum fatty acid content in C. weissflogii at Si 120 mg L⁻¹. However, the silicate-deficient conditions (Si 0 mg L⁻¹) resulted in higher levels of saturated fatty acids (38,038.62 µg g⁻¹). This study presents a practical approach for the large-scale optimization of biomass, carotenoid, fucoxanthin, and fatty acid production in C. weissflogii for commercial purposes. Full article

Fatty acids (FAs) are an essential component of the erythrocyte membrane, and nutrition and physical exercise are two variables that affect their structure and function. The aim of this study was to evaluate the erythrocyte profile in a group of high-level endurance runners, as well as the changes in different FAs, throughout a sports season in relation to the training performed. A total of 21 high-level male endurance runners (23 ± 4 years; height: 1.76 ± 0.05) were evaluated at four different times throughout a sports season. The athletes had at least 5 years of previous experience and participated in national and international competitions. The determination of the different FAs was carried out by gas chromatography. The runners exhibited low concentrations of docosahexaenoic acid (DHA) and omega-3 index (IND ω-3), as well as high values of stearic acid (SA), palmitic acid (PA), and arachidonic acid (AA), compared to the values of reference throughout the study. In conclusion, training modifies the erythrocyte FA profile in high-level endurance runners, reducing the concentrations of polyunsaturated fatty acids (PUFAs) such as DHA and AA and increasing the concentrations of saturated fatty acids (SFAs) such as SA and the PA. High-level endurance runners should pay special attention to the intake of PUFAs ω-3 in their diet or consider supplementation during training periods to avoid deficiency. Full article

Lipid-related thiamine (vitamin B1) deficiency of Baltic salmon (Salmo salar), the M74 syndrome, is generally caused by feeding on abundant young sprat (Sprattus sprattus) in the Baltic Proper, the main foraging area of these salmon. In 2014, a strong year-class of sprat was hatched in the Baltic Proper, and a strong herring (Clupea harengus) year-class was hatched in the Gulf of Bothnia, where herring is the dominant salmon prey. The fatty acid (FA) signatures of prey fish in muscle or eggs of second sea-year spawners suggested that 27% of wild River Simojoki and 68% of reared River Dal salmon remained in the Gulf of Bothnia in 2014 instead of continuing to the Baltic Proper. In 2016, 23% of the M74 females of the River Simojoki and 58% of the River Dal originated from the Gulf of Bothnia, and 13% and 16%, respectively, originated from the Baltic Proper. Some salmon from the River Neris in the southern Baltic Proper had also been feeding in the Gulf of Bothnia. In general, low free thiamine (THIAM) concentration in eggs was associated with high lipid content and high docosahexaenoic acid (DHA, 22:6n−3) and n−3 polyunsaturated FA (n−3 PUFA) concentrations in muscle but not in eggs. A higher THIAM concentration and lower proportions of DHA and n−3 PUFAs in Arctic Ocean salmon eggs, despite higher egg lipid content, indicated that their diet contained fewer fatty fish than the Baltic salmon diet. Hence, M74 originated by foraging heavily on young fatty sprat in the Baltic Proper or herring in the Gulf of Bothnia. Full article

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that exerts physiological effects via G protein-coupled receptor 120 (GPR120). In our previous studies, we figured out the inhibitory effects of DHA on TNF-α (Tumor necrosis factor-α)-induced osteoclastogenesis via GPR120 in vivo. Moreover, DHA directly suppressed RANKL expression in osteoblasts via GPR120 in vitro. In this study, we generated bone marrow chimeric mice using GPR120 deficient mice (GPR120-KO) to study the inhibitory effects of DHA on bone resorption and osteoclast formation. Bone marrow cells of wild-type (WT) or GPR120-KO mice were transplanted into irradiated recipient mice, which were WT or GPR120 deficient mice. The resulting chimeric mice contained stromal cells from the recipient and bone marrow cells, including osteoclast precursors, from the donor. These chimeric mice were used to perform a series of histological and microfocus computed tomography (micro-CT) analyses after TNF-α injection for induction of osteoclast formation with or without DHA. Osteoclast number and bone resorption were found to be significantly increased in chimeric mice, which did not express GPR120 in stromal cells, compared to chimeric mice, which expressed GPR120 in stromal cells. DHA was also found to suppress specific signaling pathways. We summarized that DHA suppressed TNF-α-induced stromal-dependent osteoclast formation and bone resorption via GPR120. Full article

The aquaculture production of pikeperch has reached commercial scale in a number of European countries, but the high mortality of early life cycle stages and minor understanding of nutritional requirements are still major bottlenecks. To investigate the fate of fatty acids during early development, weaning and rearing, pikeperch larvae and juveniles from a commercial recirculating aquaculture system (RAS) were sampled over 2 months for morphometric data, as well as fatty acid composition, with a total of 6 sampling days, with four to five replicates per sampling day and between 1 and 25 pikeperch larvae per individual sample, depending on larval biomass. The biomass of sampled pikeperch larvae varied from 0.1 to 420 mg (dry mass DM), depending on the age of the larvae, and the initial length of the pikeperch larvae was about 4.5 mm. Our data confirm that, accompanied by an exponential increase in dry mass, total fatty acids (TFAs) in larval tissues increased with the beginning of exogenous feed uptake and were depleted between days 13 and 25 post hatch, most likely associated with the weaning and metamorphosis of the larvae. We conclude that all fatty acid classes may serve as metabolic fuel during metamorphosis, but the ultimate fatty acid composition is strongly impacted by the available feed. The chosen diet probably caused a lack of alpha-linolenic (18:3n-3; ALA) and docosahexaenoic acid (22:6n-3; DHA) during larval development and a shortage of vaccenic (18:1n-7), alpha-linolenic (18:3n-3; ALA) and arachidonic acid (20:4n-6; ARA) in juvenile pikeperch. This led to low DHA/EPA ratios 13 days post hatch, a high EPA/ARA ratio at days 41 and 56 post hatch and a fluctuating ratio of alpha-linolenic acid to linoleic acid (18:2n-6; LA). A temporary lack of essential fatty acids can cause dysfunctions and eventually mortalities in pikeperch larvae and juveniles. Despite high larval growth rates, the biochemical composition of the first fed Artemia and microdiets was most likely not sufficient and in need of improvement. We suggest that deficiencies must be compensated, e.g., through the substitution of the offered Artemia with more suitable live feed organisms, such as freshwater rotifers, and the enrichment of current microdiets in order to prevent high mortalities during pikeperch rearing and weaning. Full article

Sepsis is triggered by microbial infection, injury, or even major surgery. Both innate and adaptive immune systems are involved in its pathogenesis. Cytoplasmic presence of DNA or RNA of the invading organisms or damaged nuclear material (in the form of micronucleus in the cytoplasm) in the host cell need to be eliminated by various nucleases; failure to do so leads to the triggering of inflammation by the cellular cGAS-STING system, which induces the release of IL-6, TNF-α, and IFNs. These cytokines activate phospholipase A2 (PLA2), leading to the release of polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which form precursors to various pro- and anti-inflammatory eicosanoids. On the other hand, corticosteroids inhibit PLA2 activity and, thus, suppress the release of GLA, AA, EPA, and DHA. PUFAs and their metabolites have a negative regulatory action on the cGAS-STING pathway and, thus, suppress the inflammatory process and initiate inflammation resolution. Pro-inflammatory cytokines and corticosteroids (corticosteroids > IL-6, TNF-α) suppress desaturases, which results in decreased formation of GLA, AA, and other PUFAs from the dietary essential fatty acids (EFAs). A deficiency of GLA, AA, EPA, and DHA results in decreased production of anti-inflammatory eicosanoids and failure to suppress the cGAS-STING system. This results in the continuation of the inflammatory process. Thus, altered concentrations of PUFAs and their metabolites, and failure to suppress the cGAS-STING system at an appropriate time, leads to the onset of sepsis. Similar abnormalities are also seen in radiation-induced inflammation. These results imply that timely administration of GLA, AA, EPA, and DHA, in combination with corticosteroids and anti-IL-6 and anti-TNF-α antibodies, may be of benefit in mitigating radiation-induced damage and sepsis. Full article

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice. Full article

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0–0.5 g/mL), medium (>0.5 to 1.5 g/mL), and high (>1.5 g/mL), based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid (AA), docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical–disease associations using the CTD tools and predicted an association between DHA, AA and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer’s disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, a supplement therapy may be needed to prevent omega-3 fatty acid deficiency. Full article

Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (r_AA = −0.577, p < 0.01; r_{ω-6 LCPUFA} = −0.626, p < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (OR_AA = 0.986, OR_GLA = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia. Full article

Omega-3 (ω-3) polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are involved in numerous biological processes and have a range of health benefits. DHA is obtained through the action of elongases (ELOVLs) and desaturases, among which Elovl2 is the key enzyme involved in its synthesis, and can be further metabolized into several mediators that regulate the resolution of inflammation. Our group has recently reported that ELOVL2 deficient mice (Elovl2^−/−) not only display reduced DHA levels in several tissues, but they also have higher pro-inflammatory responses in the brain, including the activation of innate immune cells such as macrophages. However, whether impaired synthesis of DHA affects cells of adaptive immunity, i.e., T lymphocytes, is unexplored. Here we show that Elovl2^−/− mice have significantly higher lymphocytes in peripheral blood and that both CD8+ and CD4+ T cell subsets produce greater amounts of pro-inflammatory cytokines in both blood and spleen compared to wild type mice, with a higher percentage of cytotoxic CD8+ T cells (CTLs) as well as IFN-γ-producing Th1 and IL-17-producing Th17 CD4+ cells. Furthermore, we also found that DHA deficiency impacts the cross-talk between dendritic cells (DC) and T cells, inasmuch as mature DCs of Elovl2^−/− mice bear higher expression of activation markers (CD80, CD86 and MHC-II) and enhance the polarization of Th1 and Th17 cells. Reintroducing DHA back into the diets of Elovl2^−/− mice reversed the exacerbated immune responses observed in T cells. Hence, impairment of endogenous synthesis of DHA exacerbates T cell inflammatory responses, accounting for an important role of DHA in regulating adaptive immunity and in potentially counteracting T-cell-mediated chronic inflammation or autoimmunity. Full article

It is commonly believed that the inactivation of inflammation is mainly due to the decay or cessation of inducers. In reality, in connection with the development of atherosclerosis, spontaneous decay of inducers is not observed. It is now known that lipid mediators originating from polyunsaturated fatty acids (PUFAs), which are important constituents of all cell membranes, can act in the inflamed tissue and bring it to resolution. In fact, PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are precursors to both pro-inflammatory and anti-inflammatory compounds. In this review, we describe the lipid mediators of vascular inflammation and resolution, and their biochemical activity. In addition, we highlight data from the literature that often show a worsening of atherosclerotic disease in subjects deficient in lipid mediators of inflammation resolution, and we also report on the anti-proteasic and anti-thrombotic properties of these same lipid mediators. It should be noted that despite promising data observed in both animal and in vitro studies, contradictory clinical results have been observed for omega-3 PUFAs. Many further studies will be required in order to clarify the observed conflicts, although lifestyle habits such as smoking or other biochemical factors may often influence the normal synthesis of lipid mediators of inflammation resolution. Full article