Long-chain Polyunsaturated Fatty Acids Research Articles

Chitosan-based delivery of fish codon-optimised Caenorhabditis elegans FAT-1 and FAT-2 boosts EPA and DHA biosynthesis in Sparus aurata

AbstractOmega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are essential fatty acids required in healthy balanced diets for humans. To induce sustained production of n-3 LC-PUFA in gilthead seabream (Sparus aurata), chitosan-tripolyphosphate (TPP) nanoparticles encapsulating plasmids expressing fish codon-optimised Caenorhabditis elegans FAT-1 and FAT-2 were intraperitoneally administered every 4 weeks (3 doses in total, each of 10 μg plasmid per g of body weight). Growth performance and metabolic effects of chitosan-TPP complexed with pSG5 (empty plasmid), pSG5-FAT-1, pSG5-FAT-2 and pSG5-FAT-1 + pSG5-FAT-2 were assessed 70 days post-treatment. Tissue distribution analysis showed high expression levels of fish codon-optimised FAT-1 and FAT-2 in the liver (> 200-fold). Expression of fat-1 and fat-1 + fat-2 increased weight gain. Fatty acid methyl esters assay revealed that co-expression of fat-1 and fat-2 increased liver production and muscle accumulation of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 LC-PUFA, while decreased the n-6/n-3 ratio. Co-expression of fat-1 and fat-2 downregulated srebf1 and genes encoding rate-limiting enzymes for de novo lipogenesis in the liver, leading to decreased circulating triglycerides and cholesterol. In contrast, FAT-2 and FAT-1 + FAT-2 upregulated hepatic hnf4a, nr1h3 and key enzymes in glycolysis and the pentose phosphate pathway. Our findings demonstrate for the first time efficient and sustained production of EPA and DHA in animals after long-term treatment with chitosan-TPP-DNA nanoparticles expressing FAT-1 and FAT-2, which enabled the production of functional fish rich in n-3 LC-PUFA for human consumption.

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants

Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants. A retrospective exploratory study of infants (n=183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center. On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period. This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population. ClinicalTrials.gov (NCT03201588).

Exploring the Potential of Atlantic Mesopelagic Species Processed on Board Commercial Fishing Vessels as a Source of Dietary Lipids.

This study investigates the use of untapped mesopelagic species as a source of long-chain polyunsaturated omega-3 fatty acids (LC n-3 PUFAs) to meet the growing demand. The challenges faced by commercial fishing vessels, such as varying catch rates and species distribution affecting lipid levels, are addressed. Marine oils were produced post-catch using thermal separation and enzymatic hydrolysis during four commercial cruises, screening approximately 20,000 kg of mixed mesopelagic species. Maurolicus muelleri and Benthosema glaciale were the dominant species in the catch, while krill was the primary bycatch. The lipid composition varied, with B. glaciale having a higher prevalence of wax esters, while triacylglycerols and phospholipids were more predominant in the other species. LC n-3 PUFAs ranged from 19% to 44% of lipids, with an average EPA + DHA content of 202 mg/g of oil. Both processing methods achieved oil recoveries of over 90%. Estimates indicate that the mesopelagic biomass in the Northeast Atlantic could supply annual recommended levels of EPA + DHA to 1.5 million people, promoting healthy heart and brain functions. These findings offer valuable insights for considering mesopelagic species as a potential source of dietary marine lipids, laying the groundwork for further research and innovation in processing and obtaining valuable compounds from such species.

Impact of FADS genotype on polyunsaturated fatty acid content in human milk extracellular vesicles: A genetic association study.

Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk. Milk was obtained from a cohort of mothers (N = 70) at 2-4 weeks of lactation. SNPs in the FADS gene locus were determined using pyrosequencing for rs174546 in FADS1 and rs174575 in FADS2. Quantitative lipidomic analysis of polyunsaturated fatty acids in human milk and extracellular vesicles from human milk was completed by gas chromatography-mass spectrometry. The rs174546 and rs174575 genotypes were independent predictors of the arachidonic acid content in extracellular vesicles. The rs174546 genotype also predicted eicosapentaenoic acid and docosahexaenoic acid in extracellular vesicles. The reduced content of long-chain polyunsaturated fatty acids in extracellular vesicles in human milk may be due to lower fatty acid desaturase activity in mothers who are carriers of the A allele in rs174546 or the G allele in rs174575. The polyunsaturated fatty acid composition of milk extracellular vesicles is predicted by the FADS genotype. These findings yield novel insights regarding extracellular vesicle content and composition that can inform the design of future research to explore how lipid metabolites impact the bioavailability of human milk extracellular vesicles.

Assessment of omega-3 and omega-6 fatty acid profiles and ratio of omega-6/omega-3 of white eggs produced by laying hens fed diets enriched with omega-3 rich vegetable oil

Abstract The aim of this study was to evaluate the levels of omega-3 (n-3) and omega-6 (n-6) fatty acids in egg and the ratio of n-6/n-3 of white eggs produced by laying hens (Hy-Line white) fed diets enriched with n-3 fats. In this study, alpha-linolenic acid (ALA) levels of the dietary treatments ranged from 0.3 to 6% energy. Grain-based diets containing a low linoleic acid (LA) content were selected to prepare a basal diet to optimize the conversion of ALA into n-3 long chain polyunsaturated fatty acids (LCPUFA). The results showed that the level of all n-3 LCPUFA in eggs improved (P < 0.01) by increasing the levels of dietary ALA. Importantly, eggs produced from laying hens fed diets containing 6%en ALA significantly increased (P < 0.01) the total of n-3 fats by approximately nine-fold. Diets enriched with ALA significantly reduced (P < 0.01) the ratio of n-6/n-3 of the eggs. The n-6/n-3 ratio of eggs decreased from 7.17% in the 0.3%en ALA diet to 1.29% in the 6%en ALA diet. In conclusion, white laying hens fed ALA-enriched diets produced eggs higher in n-3 fatty acids and lower n-6/n-3 ratio, which provides an alternative n-3 rich food for consumers and have beneficial health effects.

Lipidomic Profiling of Kidney Cortical Tubule Segments Identifies Lipotypes with Physiological Implications

Abstract A detailed knowledge of the lipid composition of components of nephrons is crucial for understanding physiological processes and the development of kidney diseases. However, the lipidomic composition of kidney tubular segments is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle's loop (cTAL) and the cortical collecting duct (CCD) from five lean and obese mice and subjected the samples to shotgun lipidomics analysis by high resolution mass spectrometry acquisition. Across all samples, more than five hundred lipid species were identified, quantified and compared. We observed significant compositional differences among the three tubular segments, which serve as true signatures. These intrinsic lipidomic features are associated with a distinct proteomic program that regulates highly specific physiological functions. The distinctive lipidomic features of each of the three segments are mostly based on the relative composition of neutral lipids, long-chain polyunsaturated fatty acids, sphingolipids, and ether phospholipids. These features support the hypothesis of a lipotype assigned to specific tubular segments. Obesity profoundly impacts the lipotype of proximal convoluted tubules. In conclusion, we present a comprehensive lipidomic analysis of three cortical segments of mouse kidney tubules. This valuable resource provides unparalleled detail that enhances our understanding of tubular physiology and the potential impact of pathological conditions.

Improvement in Muscle Fatty Acid Bioavailability and Volatile Flavor in Tilapia by Dietary α-Linolenic Acid Nutrition Strategy.

To investigate the modification of muscle quality of farmed tilapia through dietary fatty acid strategies, two diets were formulated. Diet SO, using soybean oil as the lipid source, and diet BO, using blended soybean and linseed oils, each including 0.58% and 1.35% α-linolenic acid (ALA), respectively, were formulated to feed juvenile tilapia for 10 weeks. The muscular nutrition composition, positional distribution of fatty acid in triglycerides (TAGs) and phospholipids (PLs), volatile flavor, lipid mobilization and oxidation were then analyzed. The results showed that there was no distinct difference between the SO and BO groups in terms of the nutrition composition, including crude protein, crude lipid, TAGs, PLs, and amino acid. Although the fatty acid distribution characteristics in ATGs and PLs showed a similar trend in the two groups, a higher level of n-3 PUFA (polyunsaturated fatty acid) and n-3 LC-PUFA (long-chain polyunsaturated fatty acid) bound to the glycerol backbone of TAGs and PLs was detected in the BO group than the SO group, whereas the opposite was true for n-6 PUFA. Additionally, the muscular volatile aldehyde and alcohol levels were higher in the BO group. Moreover, the expression of enzymatic genes and protein activities related to lipid mobilization (LPL, LPCAT, DGAT) and oxidation (LOX and GPX) was higher in the BO group. The results demonstrate that high-ALA diets may improve the fatty acid bioavailability and volatile flavor of tilapia by improving the lipid mobilization and oxidation, which provides new ideas for the improvement of muscle quality in farmed fish.

Association of Human Milk Fatty Acid Composition with Maternal Cardiometabolic Diseases: An Exploratory Prospective Cohort Study.

Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.

Genome-scale metabolic modeling of Thraustochytrium sp. RT2316-16: Effects of nutrients on metabolism.

Marine thraustochytrids produce metabolically important lipids such as the long-chain omega-3 polyunsaturated fatty acids, carotenoids, and sterols. The growth and lipid production in thraustochytrids depends on the composition of the culture medium that often contains yeast extract as a source of amino acids. This work discusses the effects of individual amino acids provided in the culture medium as the only source of nitrogen, on the production of biomass and lipids by the thraustochytrid Thraustochytrium sp. RT2316-16. A reconstructed metabolic network based on the annotated genome of RT2316-16 in combination with flux balance analysis was used to explain the observed growth and consumption of the nutrients. The culture kinetic parameters estimated from the experimental data were used to constrain the flux via the nutrient consumption rates and the specific growth rate of the triacylglycerol-free biomass in the genome-scale metabolic model (GEM) to predict the specific rate of ATP production for cell maintenance. A relationship was identified between the specific rate of ATP production for maintenance and the specific rate of glucose consumption. The GEM and the derived relationship for the production of ATP for maintenance were used in linear optimization problems, to successfully predict the specific growth rate of RT2316-16 in different experimental conditions.

Unwrapping the (glyco-)lipidome in the microalgae Microchloropsis gaditana: Effects of eco-friendly extraction methods

Microalgae have recently captivated worldwide attention because of their extraordinary lipid composition, which includes essential omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFA), neutral lipids, and more complex lipids (glycolipids and phospholipids), as well as eicosanoids. To explore this further, we present a novel (glyco-)lipidomics strategy, including a green chemistry extraction approach, liquid chromatography high-resolution mass spectrometry (LC-HRMS) lipid profiling, and a comprehensive data evaluation workflow. Using untargeted lipidomics based on LC-HRMS approaches, we studied the lipid composition up to the molecular species level of the microalgae Microchloropsis gaditana (formerly Nannochloropsis gaditana), focusing on the distribution of saturated, monounsaturated, and polyunsaturated fatty acids in different lipid classes. Our analysis successfully identified 520 lipid molecular species from 18 lipid classes. Regarding fatty acid composition, our primary focus was on elucidating the distribution of LC-PUFA across the different microalgal lipid classes. This particular strategy holds potential as it may unravel the use of microalgal lipids as innovative sources of food ingredients. Our findings show that LC-PUFA are relatively elevated in membrane lipids, in which cholesterol esters (ChE) have the highest PUFA share (94 %), followed by polar membrane lipids (glycolipids and phospholipids), with phosphatidylethanolamines (PE) up to 67 %, phosphatidylglycerols (PG) up to 47 %, and monogalactosyldiacylglycerols (MGDG) up to 47 % PUFA content. This highlights the high percentage of PUFA in the structural parts of microalgae and the importance of these lipid classes as a reservoir for PUFA. Finally, we also compared a classical Folch extraction method with environmentally friendly ultrasound-assisted extraction approaches and enzymatic pre-treatments to investigate the lipid composition and enrichment of valuable lipid classes. Thus, this extensive analysis of the (glyco-)lipidome of Microchloropsis gaditana provides valuable insights into the existing knowledge about this microalgae species, enhancing our understanding of the complex lipid composition and opening up new opportunities for potential applications in the biotechnology and food industry.

Characterization and Functional Analysis of Fads Reveals Δ5 Desaturation Activity during Long-Chain Polyunsaturated Fatty Acid Biosynthesis in Dwarf Surf Clam Mulinia lateralis.

Fatty acid desaturases (Fads), as key enzymes in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), catalyze the desaturation between defined carbons of fatty acyl chains and control the degree of unsaturation of fatty acids. In the present study, two Fads genes, designated MulFadsA and MulFadsB, were identified from the genome of the dwarf surf clam Mulinia lateralis (Mollusca, Mactridae), and their spatiotemporal expression was examined. MulFadsA and MulFadsB contained the corresponding conserved functional domains and clustered closely with their respective orthologs from other mollusks. Both genes were expressed in the developmental stages and all tested adult tissues of M. lateralis, with MulFadsA exhibiting significantly higher expression levels in adult tissues than MulFadsB. Subsequently, the effects of dietary microalgae on Fads expressions in the dwarf surf clam were investigated by feeding clams with two types of unialgal diets varying in fatty acid content, i.e., Chlorella pyrenoidosa (Cp) and Platymonas helgolandica (Ph). The results show that the expressions of MulFads were significantly upregulated among adult tissues in the Cp group compared with those in the Ph group. In addition, we observed the desaturation activity of MulFadsA via heterologous expression in yeasts, revealing Δ5 desaturation activity toward PUFA substrates. Taken together, these results provide a novel perspective on M. lateralis LC-PUFA biosynthesis, expanding our understanding of fatty acid synthesis in marine mollusks.

Assimilation of fish farm wastes by the ecosystem engineering bivalve Atrina zelandica

As feed-additive aquaculture expands to open ocean areas, there is concern that ecologically important habitats may be adversely impacted by sedimentation of farm wastes. In this study, we investigated assimilation of salmon faecal wastes by an ecosystem engineering bivalve that occurs in open ocean environments (Atrina zelandica), as well as effects on physiology and fatty acid metabolism. A. zelandica were subjected to one of 3 treatment diets (fish faeces, 1:1 mix of algae:faeces and algae) in a 51 d laboratory trial. We found a diet-related response in fatty acid composition, including increased prevalence of oleic acid (OA) in digestive tissues of A. zelandica fed on both the fish faeces diet and the mixed diet, indicating fish wastes were assimilated in both treatments. Fish waste consumption was related to a more marked reduction in fatty acid content of digestive gland, as well as lower proportions of long-chain polyunsaturated fatty acids (LC-PUFA) in digestive tissues. Fatty acid composition in gonad and muscle tissues was more strongly influenced by sex. Regardless of dietary treatment, females accumulated C18 fatty acids in gonad tissues, particularly OA, which may preclude the use of OA as a fish waste tracer in this organ. The accumulation of specific fatty acids according to sex may indicate a capacity for preferential selection and retention or biosynthesis of biologically important fatty acids. If present, these mechanisms may increase resilience of A. zelandica to stress from deficiencies in LC-PUFA when using fish wastes as a trophic subsidy.

Antioxidant capacity and lipid composition of Brachionus plicatilis and Artemia enriched with a mixture of different post-processing formats of Navicula salinicola and Isochrysis galbana and lipid emulsions

AbstractLive prey used by the aquaculture industry are usually poor in some essential nutrients including long chain polyunsaturated fatty acids (LC-PUFA) and must be enriched to improve their nutritional value prior to larval feeding. Standard enrichment protocols are commonly based on lipid emulsions, being associated to a high oxidative stress condition. The combination of microalgae and lipid emulsion can palliate this situation, where the oxidative stress can be partially compensated by the antioxidant compounds present in microalgae. The maintenance of living microalgae in culture facilities is laborious, and the produced biomass may present fluctuating properties, leading to a serious bottleneck in the cultivation of live prey. Hence, substitutes for live microalgae including pastes or dried formats are receiving increasing research attention due to its nutritional stability, longer shelf-life and easy handling. In this study four different microalgae formats combined with a lipid emulsion are tested as enrichment products for Brachionus plicatilis and Artemia. Thus, fresh, frozen and spray-dried Navicula salinicola (NFRE, NFRO and NSD, respectively), and spray-dried Isochrysis galbana (ISD) were mixed with a commercial oil concentrate (IncromegaTM) or a marine lecithin (LC 60®), and added for 5 h to the rotifer or Artemia culture media. The antioxidant capacity of the microalgae extracts and the live prey activity of antioxidant enzymes, peroxides index (PxI) and thiobarbituric acid reactive substances (TBARS) were evaluated. The lipid profile of microalgae formats and enriched live preys was also determined. Ethyl acetate extract was the most antioxidant active extract of all microalgae formats. In addition, overall, I. galbana seems to be better than any N. salinicola format for a more effective protection against oxidative stress and for live prey lipid enrichment. Both rotifer and Artemia cultured with the mixture of I. galbana and the lipid emulsion generally showed higher DHA/EPA and EPA/ARA ratios. Moreover, the combination of the microalgae with LC 60® lipid emulsion highly favored Artemia´s polar lipid and DHA incorporation. Among microalgae products, both spray-dried formats better enhanced live prey n-3 LC-PUFA content. Our results highlight the great potential of new microalgae-derived products to improve effectiveness of current live prey lipid enrichment protocols used in aquaculture.

Exogenous Fatty Acids Remodel the Muscle Fatty Acids Composition of the GIFT Tilapia (Oreochromis niloticus)

To reduce the negative impact of fish oil substitutes on the fatty acid composition of farmed fish, this experiment utilized different types of oils as dietary lipid sources for GIFT tilapia. Tilapia oil (FO) was used as the control, along with corn oil (CO), linseed oil (LO), algae oil (AO), and a mixture of linseed oil and algae oil in various ratios of 1 : 2, 1 : 1, and 2 : 1 (LA12, LA11, and LA21) to reshape the fatty acid profile of GIFT tilapia (0.205 ± 0.005 g) in the muscle. The weight gain and specific growth rate of tilapia in the LO and control groups were significantly higher than in other treatments (P<0.05). Meanwhile, despite the AO group exhibited the highest docosahexaenoic acid (DHA) content (P<0.05), it also exhibited the highest levels of malondialdehyde content and superoxide dismutase activity (P<0.05). The mRNA expression levels of Δ6/Δ5 fatty acyl desaturase 2 (Δ6/Δ5FADs2), Δ4 fatty acyl desaturase 2 (Δ4FADs2), acetyl-CoA carboxylase α (ACCα), and elongase of very long chain fatty acids 5 (ELOVL5) in the hepatopancreas of LO group were exhibited a significant upregulation compared to the control (P<0.05). The synthesis of DHA and eicosapentaenoic acid (EPA) in the muscles of LA12, LA11, and LA21 groups increased as the proportion of DHA decreased in the diets. In conclusion, the edible value of fatty acids of tilapia muscle, especially n-3 long-chain polyunsaturated fatty acids, can be significantly improved by adjusting the oil source in the diet through lipid metabolism.

ACSL4-mediated membrane phospholipid remodeling induces integrin β1 activation to facilitate triple-negative breast cancer metastasis.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed that metastatic TNBC tumors harbor more unsaturated phospholipids, especially long-chain polyunsaturated fatty acids, at the sn-2 position of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) compared to primary tumors. Metastatic TNBC tumors upregulated ACSL4, a long-chain polyunsaturated acyl-CoA synthetase that drives the preferential incorporation of polyunsaturated fatty acids into phospholipids, resulting in the alteration of membrane phospholipid composition and properties. Moreover, ACSL4-mediated phospholipid remodeling of the cell membrane induced lipid-raft localization and activation of integrin β1 in a CD47-dependent manner, which led to downstream focal adhesion kinase (FAK) phosphorylation that promoted metastasis. Importantly, pharmacological inhibition of ACSL4 suppressed tumor growth and metastasis and increased chemosensitivity in TNBC models in vivo. These findings indicate that ACSL4-mediated phospholipid remodeling enables TNBC metastasis and can be inhibited as a potential strategy to improve the efficacy of chemotherapy in TNBC.

Muscle biopsy long-chain omega-3 polyunsaturated fatty acid compositions, IMF and FMP in Australian pasture-based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu Beef Cattle

BackgroundWe investigated breed and gender variations in the compositions of long-chain (≥ C20) omega-3 polyunsaturated fatty acids (LC omega-3 PUFA), fat melting point (FMP) and intramuscular fat (IMF) contents in biopsy samples of the M. longissimus dorsi muscle of grazing beef cattle. The hypothesis that biopsy compositions of health-beneficial LC omega-3 PUFA, FMP and IMF in a pasture-based production system will vary with breed, was tested. Muscle biopsies were taken from 127 yearling pasture-based Angus, Hereford, and Wagyu heifers and young bulls exclusive to the Australian Bowen Genetics Forest Pastoral breeding stud averaging 12 ± 2.43 months of age and under the same management routine.ResultsBreed had a significant influence on IMF, FMP, and the compositions of oleic acid, α-linolenic acid (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA), docosapentaenoic (DPA), and total EPA + DHA + DPA in the M. longissimus dorsi muscle biopsies (P ≤ 0.03). The Wagyu breed had the highest (11.1%) and Hereford the lowest (5.9%) IMF (P = 0.03). The reverse trend was observed in FMP values where the Hereford breed had the highest (55 °C), Angus intermediate (46.5 °C), and Wagyu the lowest (33 °C) FMP. The Wagyu and Angus breeds had similar oleic fatty acid (18:1n-9) content, while the Hereford breed had the lowest (P < 0.01). The highest ALA, DPA, total EPA + DHA, total EPA + DHA + DPA and total ALA + EPA + DHA + DPA contents were detected in the Wagyu breed (P ≤ 0.03). The Hereford had similar EPA and DPA contents to the Angus (P ≥ 0.46). Total EPA + DHA + DPA contents in Wagyu, Angus, and Hereford were 28.8, 21.5, and 22.1 mg/100g tissue (P = 0.01), respectively. Sex was an important source of variation that influenced LC omega-3 PUFA composition, FMP and IMF, where yearling heifers had higher IMF (11.9% vs 5.3%), lower FMP (33°C vs 37°C), and higher LC omega-3 PUFA than bulls.ConclusionAll the results taken together indicate that the Wagyu breed at 28.8 mg/100g tissue, was the closest to meeting the Australia and New Zealand recommended source level threshold of 30 mg/100g tissue of health-beneficial ≥ C20 omega-3 FA content. Since gender was a significant determinant of LC omega-3 PUFA composition, IMF content and FMP, it should be factored into enhancement strategies of healthy meat eating quality traits in grazing cattle. These findings also suggest that the Bowen Genetics Forest Pastoral beef cattle studs are important sources of LC omega-3 PUFA that can be used to cover the deficit in these health claimable fatty acids in Western diets.

Trans isomeric fatty acids in human milk and their role in infant health and development.

It is well known that long chain polyunsaturated fatty acids (LCPUFAs) play an important role in neurodevelopment in the perinatal life. The most important source of these fatty acids is the diet, however, they can also be formed in the human body from their shorter chain precursors, the essential fatty acids. Since the WHO recommends exclusive breastfeeding for the first six months after birth, the exclusive source of these fatty acids for breastfed infants is human milk, which can be influenced by the mother's diet. Unsaturated fatty acids can have either cis or trans configuration double bond in their chain with distinct physiological effects. Cis isomeric unsaturated fatty acids have several beneficial effects, while trans isomers are mostly detrimental, because of their similar structure to saturated fatty acids. Trans fatty acids (TFAs) can be further subdivided into industrial (iTFA) and ruminant-derived trans fatty acids (rTFA). However, the physiological effects of these two TFA subgroups may differ. In adults, dietary intake of iTFA has been linked to atherosclerosis, insulin resistance, obesity, chronic inflammation, and increased development of certain cancers, among other diseases. However, iTFAs can have a negative impact on health not only in adulthood but in childhood too. Results from previous studies have shown that iTFAs have a significant negative effect on LCPUFA levels in the blood of newborns and infants. In addition, iTFAs can affect the growth and development of infants, and animal studies suggest that they might even have lasting negative effects later in life. Since the only source of TFAs in the human body is the diet, the TFA content of breast milk may determine the TFA supply of breastfed infants and thus affect the levels of LCPUFAs important for neurodevelopment and the health of infants. In this review, we aim to provide an overview of the TFA content in human milk available in the literature and their potential effects on infant health and development.

Early prey intake of a short-finned pilot whale (Globicephala macrorhynchus Gray, 1846, Cetacea: Delphinidae) in the Canary Islands.

This study reveals early prey eating by a short-finned pilot whale (Globicephala macrorhynchus Gray, 1846, Cetacea: Delphinidae) in the Canary Islands. Stomach contents, trophic markers, skin isotopic ratios of nitrogen (δ15N:15N/14N) and carbon (δ13C:13C/12C), and fatty acid profiles of the blubber of a short-finned pilot whale of 213 cm size euthanized in free-ranging conditions were analyzed. A total of 15 species of oegopsid squids, mostly diel vertical mesopelagic migrant species of the families Enoploteuthidae, Ommastrephidae, and Histioteuthidae, as well as mother's milk, were identified in the stomach contents. Asperoteuthis acanthoderma (Lu, 1977, Cephalopoda: Chiroteuthidae) was found as first time in this area, suggesting the possibility of its presence on both sides of the subtropical Atlantic, extending its current known distribution. The δ15N value (11.55‰) was higher than expected based on the size range of squid ingested, but lower than that of adult pilot whales, suggesting that mother's milk intake has a significant effect on these values in calves. Similarly, the δ13C values (-17.99‰) were shifted to those of adult pilot whales rather than the ingested squids, also due to the ingestion of high-fat breast milk. The fatty acid (FA) composition of blubber showed a clear stratification. Long-chain polyunsaturated fatty acids (LC-PUFA) were mainly present in the inner layer, while most relevant ≤C20 monounsaturated fatty acids (MUFA) were more abundant in the outer layer.

Proximate and fatty acids composition in the muscle of wild and farmed sardine (Sardinella brasiliensis)

Wild sardines contain a high level (2560 mg/100 g n-3 LC-PUFA of wet mass) of long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA), namely, PUFA with 20 and 22 carbon atoms, however, in captivity their fatty acid composition can be affected by food and farming conditions. Therefore, this study evaluated the proximate composition and fatty acid profile of sardines cultivated in the four seasons of the year as well as compared to those captured in the wild in the spring. In both analyses, farmed sardines differed significantly from wild specimens. Total lipid content was significantly higher, especially in winter, with 14.52 % and 2.37 % for farmed and wild sardines, respectively. The fatty acid profile had a prevalence of n-3 LC-PUFA in wild fish (17.6 %) and n-6 PUFA ​​in farmed fish (12.2 %). LC-PUFA showed higher relative levels in wild animals, 16.4 % against 1.2 % for farmed sardines in winter. In absolute terms, the amount of EPA (eicosapentaenoicacid) and DHA (docosahexaenoicacid) in farmed sardine was similar to the wild specimens in spring 4000 mg/100 g and 3000 mg/100 g, respectively.