Docosahexaenoic Acid Research Articles

Higher docosahexaenoic acid proportions in blood are inversely associated with the prevalence of prediabetes: Evidence from the UK Biobank

Prediabetes and type 2 diabetes mellitus are growing global health concerns, predisposing individuals to various vascular complications. Lifestyle modifications, including dietary interventions, offer promising avenues for prevention and management. Using a multivariable-adjusted model, we analyzed the cross-sectional associations between plasma proportions (% of total fatty acids) of omega-3 polyunsaturated fatty acids (n3 PUFA, including total n3 PUFA, docosahexaenoic acid [DHA], non-DHA n3 PUFA), and glycated hemoglobin A1c (HbA1c) as well as the prevalence of prediabetes in a sample from the UK Biobank cohort. Our hypothesis was that proportions of n3 PUFA, especially DHA, would by inversely associated with the prediabetes prevalence. The sample (n = 92,762; 54.5% females) had an average age of 56 years and was overweight (mean body mass index = 27). The mean plasma DHA proportion in the sample was 2.03% (standard deviation [SD] = 0.67%), non-DHA n3 PUFA was 2.41% (SD = 1.02%) and total n3 PUFA was 4.43% (SD = 1.56%). Prediabetic individuals were identified by blood HbA1c proportions between 5.7% and 6.4% (39-46 mmol/mol) according to American Diabetes Association criteria. Each of the three n3 PUFA biomarkers was inversely associated with HbA1c proportions. In particular, DHA showed the strongest inverse association, with an OR of 0.62 (95% confidence intervals: 0.58, 0.67; P < .001) when comparing quintiles 5 to 1 in a fully adjusted model. These findings suggest a potential protective role of n3 PUFA, particularly DHA, in mitigating the risk of having prediabetes. Further prospective investigations are needed to clarify whether long-chain n3 PUFA could function as modifiable factors for prediabetes.

Influence of Lipid Class Used for Omega-3 Fatty Acid Supplementation on Liver Fat Accumulation in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.

Molecular Insights into Single Chain Lipid Modulation of Acid-Sensing Ion Channel 3.

Polyunsaturated fatty acids (PUFAs) and their analogs play a significant role in modulating the activity of diverse ion channels, and recent studies show that these lipids potentiate acid-sensing ion channels (ASICs), leading to increased activity. The potentiation of the channel stems from multiple gating changes, but the exact mechanism of these effects remains uncertain. We posit a mechanistic explanation for one of these changes in channel function, the increase in the maximal current, by applying a combination of electrophysiology and all-atom molecular dynamics simulations on the open-state hASIC3. Microsecond-scale simulations were performed on open-state hASIC3 in the absence and presence of a PUFA, docosahexaenoic acid (DHA), and a PUFA analog, N-arachidonyl glycine (AG). Intriguingly, our simulations in the absence of PUFA or PUFA analogs reveal that a tail from the membrane phospholipid POPC inserts itself into the pore of the channel through lateral fenestrations on the sides of the transmembrane segments, obstructing ion permeation through the channel. The binding of either DHA or AG prevented POPC from accessing the pore in our simulations, relieving the block of ionic conduction by phospholipids. Finally, we use the single-channel recording to show that DHA increases the amplitude of the single-channel currents in ASIC3, which is consistent with our hypothesis that PUFAs relieve the pore block of the channel induced by POPCs. Together, these findings offer a potential mechanistic explanation of how PUFAs modulate ASIC maximal current, revealing a novel mechanism of action for PUFA-induced modulation of ion channels.

Utilization of Aquatic Plants and Microalgae for Sustainable Aquaculture Production and Potential Biotechnological Applications

Locally available feedstuffs, such as grain seed cakes, oilseeds, and vegetable waste, hold immense potential as alternative feed sources in fish farming. However, these plant-based ingredients have low crude protein content and lack essential fatty acids, which lowers palatability and feed conversion efficiencies, leading to suboptimal fish growth. Traditional feedstuffs like fishmeal and soybean meal face sustainability challenges such as local unavailability, the presence of anti-nutritional factors, and energy-intensive processing. The rising costs of commercial aqua-feeds and feed scarcity necessitate exploring alternative fish feed options. Aquatic plants like Ipomoea aquatica, Lemna minor, and Azolla pinnata, along with green and blue-green microalgae such as Chlorella spp. and Arthrospira spp. (Spirulina), are promising alternatives due to their high protein content, availability of essential omega-3 fatty acids such as EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid), and beneficial bioactive compounds. These plants and microalgae, with crude protein content ranging from 25% to 65%, can significantly enhance fish growth, health, and product quality by partially or entirely replacing fishmeal. Their nitrogen-fixing abilities contribute to their high protein levels. Additionally, these organisms have various biotechnological applications, including phytoremediation, Integrated Multi-trophic Aquaculture (IMTA), aquaponics, biofloc technology, and constructed wetlands. Despite their potential, challenges in scaling up and integrating these alternatives into existing systems remain. Collaborative efforts and advocacy among farmer groups are crucial for knowledge sharing and fostering sustainable biotechnological solutions. Long-term strategies should focus on upscaling local feed production and research and development to achieve self-sufficiency and cost-effective natural feed production systems in fish farming.

A phylogenetic approach for identifying new sources of economically important fatty acids in plants and algae

Societal Impact StatementNew sources of essential and other nutritionally and/or pharmacologically important fatty acids for human use can be discovered through bioprospecting. Demonstrating how fatty acids in plants and algae are distributed across a phylogeny is a critical first step in this process. Here, new sources of essential omega‐3 fatty acids that are critically important to human health were identified, such as green and Chromista algae, bryophytes and some angiosperm families. The identification of certain taxa that are high in critical fatty acids is important for developing new sources of these healthful compounds.Summary Essential fatty acids (EFA) including long‐chain omega‐3 and omega‐6 EFA are key nutrients that broadly support the health of individuals and the ecosystems they inhabit. Production of these EFA is critical to global nutritional security, and therefore, it is imperative to assess the distribution patterns of FA in plants to bioprospect new resources that do not threaten biodiversity. We used a meta‐analytic approach (phylogenetic signal analysis), which incorporated a wide variety of taxa to map FA profiles including both presence and abundance of specific FA and EFA onto a plant phylogeny including algae, bryophytes, pteridophytes, gymnosperms and angiosperms. Our phylogenetic signal analysis revealed that presence/absence of most FA of interest were randomly or ubiquitously distributed, while FA content was significantly clustered in specific clades for most key FA (including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and nervonic acid). Both green and Chromista algae displayed relatively high proportions of EPA and DHA, while green algae contained higher proportional amounts of stearidonic acid (SDA). Further, signal analysis revealed high proportional content of gamma‐linoleic acid (GLA) in bryophytes and some angiosperm families, suggesting potential sources for bioprospecting GLA. This analysis provides a crucial foundation for understanding the influence of phylogenetic relationships in the relative proportions of key FA in plants and algae across a diverse phylogeny. Furthermore, in demonstrating how fatty acids in plants and algae are distributed across a phylogeny, we provide a critical first step in bioprospecting for new sources of essential and other nutritionally‐ and/or pharmacologically important fatty acids for human use.

Is per capita fish consumption in Latin America aligned with international recommendations for a healthy diet?

The World Health Organization (WHO) is urging Latin American countries to prioritize the prevention of chronic noncommunicable diseases. Diet is a crucial factor in determining one’s health, and healthy eating recommendations emphasize the consumption of fish at least twice a week due to its protein, vitamin, mineral, and essential fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This review was designed to compare the status of fish consumption as a source of EPA and DHA fatty acids in some Latin American countries (namely Brazil, Chile, Colombia, and Ecuador), and comparisons with international recommendations within a healthy diet could contribute to the WHO’s call for a focus on preventing the aforementioned diseases in the region. A comprehensive literature search was conducted from January to October 2022 using PubMed, Scopus, EBSCO, and government compendia. Keywords included “fish,” “consumption,” “fatty acids,” “nutrients,” and “Latin America;” and “fish,” “chronic non-communicable diseases,” “all-cause mortality,” “obesity,” “cancer,” “neurodegenerative diseases,” “metabolic diseases,” “diabetes,” “polycystic ovary syndrome,” and “metabolic syndrome.” In countries such as Chile, Brazil, and Colombia, per capita fish consumption falls below WHO’s recommended levels, and the most commonly eaten species do not contain sufficient polyunsaturated fatty acids to provide an optimal intake of EPA and DHA. It is therefore recommended that each country review its dietary guidelines and fish recommendations based on the most commonly consumed species to ensure that their populations obtain the recommended intake of EPA and DHA fatty acids and thus the benefits related to the prevention of chronic noncommunicable diseases.

Effect of docosahexaenoic acid as an anti-inflammatory for Caco-2 cells and modulating agent for gut microbiota in children with obesity (the DAMOCLE study).

Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid. We investigated the dual health ability of DHA to modulate gut microbiota in children with obesity and to exert anti-inflammatory activity on human intestinal Caco-2 cells. In a pilot study involving 18 obese children (8-14years), participants received a daily DHA supplement (500mg/day) and dietary intervention from baseline (T0) to 4months (T1), followed by dietary intervention alone from 4months (T1) to 8months (T2). Fecal samples, anthropometry, biochemicals and dietary assessment were collected at each timepoint. At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (H2O2) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase(iNOS) levels and cytokines, respectively. Ten children were included in final analysis. No major changes were observed for anthropometric and biochemical parameters, and participants showed a low dietary compliance at T1 and T2. DHA supplementation restored the Firmicutes/Bacteroidetes ratio that was conserved also after the DHA discontinuation at T2. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In Caco-2 cells, DHA decreased H2O2-induced reactive oxygen species (ROS) and nitric oxide (NO) production via iNOS pathway modulation. Additionally, DHA modulated proinflammatory (IL-1β, IL-6, IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokine production in LPS-stimulated Caco-2 cells. An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. The ability to modulate gut microbiota, matches also with an anti-inflammatory effect of DHA on Caco-2 cells.

Pericyte-to-Endothelial Cell Communication via Tunneling Nanotubes Is Disrupted by a Diol of Docosahexaenoic Acid.

The pericyte coverage of microvessels is altered in metabolic diseases, but the mechanisms regulating pericyte-endothelial cell communication remain unclear. This study investigated the formation and function of pericyte tunneling nanotubes (TNTs) and their impact on endothelial cell metabolism. TNTs were analyzed in vitro in retinas and co-cultures of pericytes and endothelial cells. Using mass spectrometry, the influence of pericytes on endothelial cell metabolism was examined. TNTs were present in the murine retina, and although diabetes was associated with a decrease in pericyte coverage, TNTs were longer. In vitro, pericytes formed TNTs in the presence of PDGF, extending toward endothelial cells and facilitating mitochondrial transport from pericytes to endothelial cells. In experiments with mitochondria-depleted endothelial cells displaying defective TCA cycle metabolism, pericytes restored the mitochondrial network and metabolism. 19,20-Dihydroxydocosapentaenoic acid (19,20-DHDP), known to disrupt pericyte-endothelial cell junctions, prevented TNT formation and metabolic rescue in mitochondria-depleted endothelial cells. 19,20-DHDP also caused significant changes in the protein composition of pericyte-endothelial cell junctions and involved pathways related to phosphatidylinositol 3-kinase, PDGF receptor, and RhoA signaling. Pericyte TNTs contact endothelial cells and support mitochondrial transfer, influencing metabolism. This protective mechanism is disrupted by 19,20-DHDP, a fatty acid mediator linked to diabetic retinopathy.

Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer

AimsThe recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive. MethodsDrug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function. ResultsNUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3’UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells. ConclusionsThe un-methylation of NUDT21-mediated 3’UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.

Intravenous lipid emulsions designed to meet preterm infant requirements increase plasma and tissue levels of docosahexaenoic acid and arachidonic acid in mice

Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity. Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days. Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2±0.3 vs. 19.3±0.3%, P=1.00) and ARA (10.4±0.2 vs. 9.9±0.2% ARA, P=0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments. Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration.

Docosahexaenoic acid enhances the treatment efficacy for castration-resistant prostate cancer by inhibiting autophagy through Atg4B inhibition

Autophagy induction in cancer is involved in cancer progression and the acquisition of resistance to anticancer agents. Therefore, autophagy is considered a potential therapeutic target in cancer therapy. In this study, we found that long-chain fatty acids (LCFAs) have inhibitory effects on Atg4B, which is essential for autophagosome formation, through screening based on the pharmacophore of 21f, a recently developed Atg4B inhibitor. Among these fatty acids, docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibited the most potent Atg4B inhibitory activity. DHA inhibited autophagy induced by androgen receptor signaling inhibitors (ARSI) in LNCaP and 22Rv1 prostate cancer cells and significantly increased apoptotic cell death. Furthermore, we investigated the effect of DHA on resistance to ARSI by establishing darolutamide-resistant prostate cancer 22Rv1 (22Rv1/Dar) cells, which had developed resistance to darolutamide, a novel ARSI. At baseline, 22Rv1/Dar cells showed a higher autophagy level than parental 22Rv1 cells. DHA significantly suppressed Dar-induced autophagy and sensitized 22Rv1/Dar cells by inducing apoptotic cell death through mitochondrial dysfunction. These results suggest that DHA supplementation may improve prostate cancer therapy with ARSI.

Impact of adding eicosapentaenoic and docosahexaenoic acid-rich fish oil in sow and piglet diets on blood oxylipins and immune indicators of weaned piglets

Weaning is a decisive event in piglets’ life. This study aimed to evaluate whether the inclusion of fish oil, rich in eicosapentaenoic and docosahexaenoic acids (EPA and DHA), in sow and piglet diets, increased the concentration of anti-inflammatory molecules in the blood of weaned piglets and whether the effect was dependent on the pigs being born with either low or a high birth BW (bBW). Thirty-six sows in four consecutive batches were randomly distributed between a control diet with animal fat (15 g/kg in gestation and 30 g/kg in lactation) or a n-3 long-chain fatty acid diet (LCFA; totally or half replacing animal fat by fish oil during gestation and lactation, respectively) from service until weaning (ca. 28 days). At birth, the two lightest (LBW) and the two heaviest (HBW) piglets in each litter were identified and, at weaning, grouped in pens by pairs prioritising their bBW. Pens were further distributed into a control (30 g/kg animal fat) or n-3 LCFA diet (totally replacing animal fat by fish oil) for 28 days. At the end of the trial, blood was collected from piglets in the first batch (n = 48). Serum fatty acids (FAs) were quantified by GC, plasma oxylipins by ultra-HPLC-MS, and plasma immune indicators by ELISA. An interaction between piglet diet and bBW for average daily gain (P = 0.020) and average daily feed intake (P = 0.014) during the whole postweaning indicated that dietary n-3 LCFA−promoted LBW piglets to have a similar growth and intake than HBW piglets reaching 1.5 kg average BW more at the end of the postweaning period than LBW control piglets. Fish oil in piglet diets also increased the concentrations of total n-3 FA, EPA and DHA (all P < 0.001), their resultant oxylipins, particularly their hydroxy derivatives from lipoxygenase enzymatic pathway (all P < 0.001) and tended to increase immunoglobulin M (P = 0.067) in blood. Regarding the bBW category, LBW piglets tend to increase tumour necrosis factor α in plasma (P = 0.083) compared to HBW. It is concluded that fish oil in postweaning diets could enhance the daily gain and feed intake of LBW piglets, increasing the concentration of serum n-3 FAs and their derived oxylipins in plasma.

Association of maternal blood and umbilical cord blood plasma fatty acid levels with the body size at birth of Japanese infants

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly obtained from fish, have been implicated in fetal development. Because few studies have examined maternal and umbilical cord blood fatty acid levels and infant body size in Japan with a fish-eating culture, we examined differences in plasma fatty acid levels in pregnant women and infant size at birth. This study is a large birth cohort study of 1476 pairs of Japanese pregnant women and their infants. Maternal blood DHA levels and infant birth weight showed a positive relationship. However, analysis adjusted for gestational age did not reveal correlations. Negative relationships were found between cord blood DHA levels and infant body size, and between the difference in mother-to-child DHA levels and infant body size. Thus, the smaller the birth size, the higher the differences in umbilical cord blood DHA levels and mother-to-child DHA levels when considering gestational age.

Comparative analysis of Scarb1 and Cd36 in grass carp (Ctenopharyngodon idellus): Implications for DHA uptake

The polyunsaturated fatty acid docosahexaenoic acid (DHA) significantly influences fish growth and lipid metabolism. Nevertheless, the specific mechanism by which DHA is transported and exerts its effects remains unclear. Scavenger receptor class B type I (SCARB1) is essential for maintaining cellular cholesterol levels and regulating the immune system in mammals, as well as facilitating the uptake of fatty acids (FAs). Another class B scavenger receptor, cluster-determinant 36 (CD36), is involved in promoting the uptake and transport of long-chain fatty acids. However, the molecular characteristics of the grass carp scarb1 gene have not yet been reported, and the potential role of Scarb1 and Cd36 in mediating DHA transport and metabolism remains uncertain. This study aimed to investigate the effects of Scarb1 and Cd36 on DHA transport. Initially, grass carp scarb1–1 and scarb1–2 were cloned. Predictions were made regarding their structural characteristics, including number and presence of transmembrane domains and glycosylation sites. Furthermore, gene structure analysis revealed that scarb1–1 has two additional exons in the 3′-region compared to scarb1–2. The multiple sequence alignment indicated that Scarb1 exhibits conserved motifs and amino acid residues across vertebrates. mRNA expression of scarb1–1 was the highest in the intestine, while scarb1–2 was highest expressed in adipose tissue, with both having lower expression levels in muscle tissue. Scarb1–1 was primarily localized on the cell membrane, whereas Scarb1–2 was found in both the cell membrane and cytoplasm. After overexpression of grass carp Scarb1–1, Scarb1–2, and Cd36 in HEK 293 T cells, DHA incubation showed that only Cd36 significantly increased cellular DHA relative content, suggesting a potential role of Cd36 in DHA transport. These findings will serve as a basis for further research on fatty acid transport in fish.

Docosahexaenoic acid insufficiency impairs placental angiogenesis by repressing the methylene-bridge fatty acylation of AKT in preeclampsia

IntroductionPreeclampsia (PE), characterised by hypertension in pregnancy, is regarded as a placental metabolism-related syndrome affecting 5–8% of pregnancies worldwide. The insufficiency of polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), is a causative factor of PE pathogenesis. However, its molecular aetiology is yet to be comprehensively elucidated. MethodsCRISPR/Cas9 was used to construct Fads2 knockout mice. Gas chromatography–mass spectrometry was used to detect placental fatty acid levels. Gene Expression Omnibus was used to analyze placental FADS2 mRNA levels. CCK-8 assay was used to assess cell growth capacity. Cell migration and invasion abilities were measured by transwell and wound healing assay. Tube forming assay was used to test angiogenesis ability. The co-immunoprecipitation assay was used to validate interactions between two proteins. AKT inhibitor MK-2206 and methylene-bridge fatty acylation inhibitor tryptophan were used to rescue experiments. ResultsCompared to those in women with normal pregnancies, the DHA levels in the placentas of patients with PE decreased with the downregulation of FADS2, the key desaturase in the synthesis of PUFAs. Pregnant Fads2+/− mice exhibited PE-like symptoms, including proteinuria and elevated systolic arterial blood pressure, due to defective placental angiogenesis. Mechanistically, FADS2 knockdown in trophoblasts decreased cellular DHA levels and repressed the methylene-bridge fatty-acylation of AKT, inhibiting AKT-VEGFA signalling, which is crucial for angiogenesis. DiscussionOur results suggest that placental DHA insufficiency downregulates placental angiogenesis via inhibiting fatty acylating AKT and AKT-VEGFA signalling, a novel insight into abnormal fatty acid metabolism in PE.

Biosynthesis of long-chain polyunsaturated fatty acids in the nereid polychaete Hediste diversicolor: Molecular cloning and functional characterisation of three fatty acyl elongases and two front-end desaturases

Aquaculture of carnivorous fish species heavily relies on marine ingredients to guarantee the provision of essential nutrients, including long-chain (C20–24) polyunsaturated fatty acids (LC-PUFA) such as arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3). These nutrients are crucial for fish growth and neural development, offering significant health benefits to consumers. The rapid growth of global aquaculture production in recent decades, has driven the exploration of alternative and sustainable feeding sources that ensure n-3 LC-PUFA content. Within the context of circular economy, polychaete worms arise as promising candidates for aquafeed formulations, due to the enzymatic capacity for de novo LC-PUFA biosynthesis. The present study focused on the molecular and functional characterisation of elongases (Elovl) and front-end desaturases (Fed) involved in the LC-PUFA biosynthesis of the nereid polychaete Hediste diversicolor. The sequence and phylogenetic analysis established the orthology of three Elovl, identified as Elovl2/5, Elovl4 and Elovl1/7, that have putative functions in the LC-PUFA biosynthesis. Functional characterisation in yeast demonstrated their roles as PUFA elongases, exhibiting affinity towards C18 and C20 PUFA substrates (Elovl2/5) and towards C18, C20 and C22 (Elovl4 and Elovl1/7). Additionally, H. diversicolor possesses two front-end desaturases (Fed1 and Fed2) with Δ5 and Δ6/Δ8 desaturation activities, respectively, thus encompassing all the necessary desaturation reactions involved in the LC-PUFA biosynthesis pathways. These findings, along with the previously characterised methyl-end desaturases, show that H. diversicolor possesses the full enzymatic repertoire necessary to produce LC-PUFA like ARA and EPA. This highlights the potential of polychaetes and other annelids for producing nutrient-rich biomass suitable for aquaculture.

Examining performance, milk, and meat in ruminants fed with macroalgae and microalgae: A meta-analysis perspective.

This meta-analysis consolidates various related studies to identify patterns in the impact of feeding algae on performance aspects, including milk fat, milk protein, and carcass yield in several ruminant species, such as cattle, sheep, and goats. The data were collected from 67 articles that examined factors such as the type of algae (macro- and microalgae), algal species, and animal breed. Barki sheep, Moghani sheep, and Zaraibi goats demonstrated an increased average daily gain (P < 0.05) when fed with both macro- and microalgae. Conversely, sheep such as Canadian Arcott and Ile-de-France showed adverse effects on the feed conversion ratio (FCR) (P < 0.05). Elevated FCR values were observed across castrated and young animals (P < 0.05). Algae extract notably increased the hot carcass weight (P < 0.001), particularly among Moghani sheep (P < 0.001). Raw algae significantly reduced the milk fat content (P < 0.001), particularly in cattle and sheep (P < 0.001). A decrease in milk fat was particularly noticeable in lactating females of Assaf sheep, Damascus goats, and Holstein cows (P < 0.001). Overall, algae inclusion tended to decrease the milk protein content (P < 0.05), leading to reduced milk production (P < 0.001) with cumulative algae feeding in Assaf sheep. However, conjugated linoleic acid (CLA; C18:2 c9,t11-CLA and C18:2 c12,t10-CLA) and docosahexaenoic acid (DHA; C22:6n-3) mostly increased in meat and milk from Holstein cow, Assaf sheep, Dorset sheep, and Ile-de-France sheep (P < 0.01). This meta-analysis highlights the necessity for additional research aimed at optimizing the sustainable use of algae in feed for ruminants, despite the demonstrated improvements in performance and the levels of CLA and DHA found in meat and milk.

Effects of feeding patterns on production performance, lipo-nutritional quality and gut microbiota of Sunit sheep

This study aimed to investigate the impact of feeding patterns on the production performance, lipo-nutritional quality, and gut microbiota of Sunit sheep. A total of 24 sheep were assigned to two groups: confinement feeding (CF) and pasture feeding (PF) groups. After 90 days, the CF group exhibited significantly increased average daily gain, carcass weight, backfat thickness, and intramuscular fat content of the sheep, whereas the PF group showed significantly increased pH24h and decreased L∗ value and cooking loss of the longissimus lumborum (LL) muscle (P < 0.05). In the PF group, the contents of linoleic, α-linolenic, and docosahexaenoic acids were considerably higher and the n-6/n-3 polyunsaturated fatty acid ratio was significantly lower (P < 0.05). Furthermore, the triglyceride, cholesterol, and nonesterified fatty acid levels in the serum of the CF group significantly increased, whereas the enzyme contents of fatty acid synthase (FASN) and hormone-sensitive lipase (HSL) in the LL muscle of the PF group were markedly elevated (P < 0.05). The PF group also showed altered expression of lipid metabolism-related genes, including upregulated FASN, HSL, fatty acid binding protein 4 (FABP4), and peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α) (P < 0.05). Meanwhile, differences were observed in the abundance of key bacteria and microbiota functions between the groups. Correlation analysis revealed that production performance and lipid metabolism may be related to the differential effects of bacteria. In conclusion, the transition in the feeding patterns of Sunit sheep caused changes in the gut microbial community and lipid metabolism level in the muscle as well as differences in fat deposition and meat quality.

Biosynthetic mechanisms of omega-3 polyunsaturated fatty acids in microalgae

Marine microalgae are the primary producers of ω3 polyunsaturated fatty acids (PUFAs), such as octadecapentaenoic acid (OPA, 18:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) for food chains. However, the biosynthetic mechanisms of these PUFAs in the algae remain elusive. To study how these fatty acids are synthesized in microalgae, a series of radiolabeled precursors were used to trace the biosynthetic process of PUFAs in Emiliania huxleyi. Feeding the alga with 14C-labeled acetic acid in a time course showed that OPA was solely found in glycoglycerolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) synthesized plastidically by sequential desaturations while DHA was exclusively found in phospholipids synthesized extraplastidically. Feeding the alga with 14C-labeled α-linolenic acid (ALA), linoleic acid (LA) and oleic acid (OA) showed that DHA was synthesized extraplastidically from fed ALA and LA, but not from OA, implying that the aerobic pathway of DHA biosynthesis is incomplete with missing a Δ12 desaturation step. The in vitro enzymatic assays with 14C-labeled malonyl-CoA showed that DHA was synthesized from acetic acid by a PUFA synthase. These results provide the first and conclusive biochemistry evidence that OPA is synthesized by a plastidic aerobic pathway through sequential desaturations with the last step of Δ3 desaturation, while DHA is synthesized by an extraplastidic anaerobic pathway catalyzed by a PUFA synthase in the microalga.

Self-Assembled Protein Micelles for Encapsulation of Docosahexaenoic Acid (DHA): The Improvement of Bioaccessibility and Lipid-Lowering Activity

Self-Assembled Protein Micelles for Encapsulation of Docosahexaenoic Acid (DHA): The Improvement of Bioaccessibility and Lipid-Lowering Activity