Chain Polyunsaturated Fatty Acids Research Articles

Review on the fatty acid profile and free fatty acid of common carp (Cyprinus carpio)

Carp or ponty in Hungarian, is considered commercial freshwater fish, which is an adaptable species in both wild and cultured conditions. Carp has high nutritional value content, favorable taste, it is rich in protein, and low in saturated fat. The nutritional content in fish is composed of many chemical constituents and influenced by many factors. One of the components that its content may be different due to internal and external factors is fatty acids, which may vary depending on endogenous and exogenous factors. The endogenous or internal factors include the genetic, size, sexual maturity, and life cycle phase. While microclimate, water quality, quality of food or diet habit, and the amount of available food or starvation are considered as exogenous or environmental factors. Freshwater fish has the ability to convert essential fatty acid into long chain polyunsaturated fatty acid like AA, EPA, and DHA. Most results showed that palmitic acid and oleic acid were the dominant SFA and MUFA in carp both for wild and farmed carp in all seasons. The PUFA for wild carp was mainly dominated by DHA, while on farmed carp by LA. It confirmed that high LA content in farmed carp was related to the diet habit. The amount of lipid and FA were changed in line with the season. Even the statistical analysis showed no significant difference, but some studies showed a contrasting result. Moreover, most obtained results acknowledged that FA tends to decrease during the spawning period. The amount and composition of FA were affected by the total lipid content. The lipid must be broken down into simpler compounds such as FA or FFA for the metabolism of fish. The result of metabolism then transported into the utilising tissue and used as energy.

Knockdown of Placental Major Facilitator Superfamily Domain Containing 2a in Pregnant Mice Reduces Fetal Brain Growth and Phospholipid Docosahexaenoic Acid Content.

Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid critical for fetal brain development that is transported to the fetus from the mother by the placenta. The lysophosphatidylcholine (LPC) transporter, Major Facilitator Superfamily Domain Containing 2a (MFSD2a), is localized in the basal plasma membrane of the syncytiotrophoblast of the human placenta, and MFSD2a expression correlates with umbilical cord blood LPC-DHA levels in human pregnancy. We hypothesized that placenta-specific knockdown of MFSD2a in pregnant mice reduces phospholipid DHA accumulation in the fetal brain. Mouse blastocysts (E3.5) were transduced with an EGFP-expressing lentivirus containing either an shRNA targeting MFSD2a or a non-coding sequence (SCR), then transferred to pseudopregnant females. At E18.5, fetuses were weighed and their placenta, brain, liver and plasma were collected. MFSD2a mRNA expression was determined by qPCR in the brain, liver and placenta and phospholipid DHA was quantified by LC-MS/MS. MFSD2a-targeting shRNA reduced placental mRNA MFSD2a expression by 38% at E18.5 (n = 45, p < 0.008) compared with SCR controls. MFSD2a expression in the fetal brain and liver were unchanged. Fetal brain weight was reduced by 13% (p = 0.006). Body weight, placenta and liver weights were unaffected. Fetal brain phosphatidyl choline and phosphatidyl ethanolamine DHA content was lower in fetuses with placenta-specific MFSD2a knockdown. Placenta-specific reduction in expression of the LPC-DHA transporter MFSD2a resulted in reduced fetal brain weight and lower phospholipid DHA content in the fetal brain. These data provide mechanistic evidence that placental MFSD2a mediates maternal-fetal transfer of LPC-DHA, which is critical for brain growth.

Supplementation of gilthead seabream (Sparus aurata) diets with spices as a functional strategy to control excess adiposity through lipid, cholesterol and bile acid metabolism, and to induce an immunomodulatory intestinal regulation

Reductions in fish oil content in aquafeeds can generate physiological and immunological disorders in farmed fish, associated to low dietary levels of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs) and increased levels of n-6 PUFAs. Based on mammalian literature, spices could potentially counteract some of these negative effects. To explore this hypothesis, this work intended to offer a holistic insight on the effect of supplementing a diet (44% crude protein, 18% crude fat, 21.4 MJ kg−1 gross energy) containing low (3%) fish oil and poultry fat as the main oil source (43% of added oils) with 0.2% of an encapsulated combination of spice oleoresins (SO) including turmeric, capsicum, black pepper, and ginger in gilthead seabream (Sparus aurata, 44.1 ± 4.1 g). At the end of the trial (90 days), fish fed with the SO diet displayed lower levels of perivisceral and hepatic fat, as well as reduced accumulation of lipid deposits, assessed histologically, in liver and intestine. These findings were consistent with an increased activity of bile salt-activated lipase in the anterior intestine and the regulation of gene expression (qPCR) of several biomarkers related to lipid metabolism, including several key metabolic sensors and nuclear factors (hnf4a and srebp2 at 2 h after feeding and lxrα, fxr, pparγ, pparβ, sirt1 in 48 h-fasted fish) that coordinate the expression of a network of genes (many of them significantly affected herein) regulating lipid, cholesterol and bile acid homeostasis. Moreover, the combination of SO had an immunomodulatory effect in the intestine which reached its climax in 48 h fasted-fish with the down-regulation of the pro-inflammatory cytokines tnf-α, il-12β, il-15, il-34 and cell markers cd4–1, cd8b, and ccr11, suggesting a potential anti-inflammatory response. No major effects were noted on fish growth and feed performance, on the oxidative status of the fish (although there were some subtle indications of reduced hepatic ROS levels). When assessing the gut microbial communities of gilthead seabream (16S rRNA gene sequencing on Illumina MiSeq) there were no differences in alpha and beta diversity between both experimental diets in the anterior and posterior intestines, except for an increase in the relative abundance of Bacteroides, Desulfovibrio, Candidatus Arthromitus, and Ralstonia. In conclusion, supplementation of diets with the tested combination of SO may be an effective strategy to prevent lipid accumulation and inflammation in fish fed diets containing reduced fish oil levels.

Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies

Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson’s disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration.

HAMLET in human milk is resistant to digestion and carries essential free long chain polyunsaturated fatty acids and oleic acid.

The oleic acid/alpha-lactalbumin complex HAMLET (human alpha-lactalbumin made lethal to tumors) is cytotoxic to various cancerous cell lines and is assembled from alpha-lactalbumin (ALA) and free oleic acid (OA). HAMLET is also cytotoxic to normal immature intestinal cells. It remains unclear if HAMLET, experimentally assembled with OA and heat, can spontaneously assemble in frozen human milk over time. To approach this issue, we used a set of timed proteolytic experiments to evaluate the digestibility of HAMLET and native ALA. The purity of HAMLET in human milk was confirmed by ultra high performance liquid chromatography coupled to tandem mass spectrometry and western blot to resolve the ALA and OA components. Timed proteolytic experiments were used to identify HAMLET in whole milk samples. Structural characterization of HAMLET was performed by Fournier transformed infrared spectroscopy and indicated a transformation of secondary structure with increased alpha-helical character of ALA upon binding to OA.

Malformed jaw phenotype and replacement of dietary fish oil by olive oil affect fatty acid composition, antioxidant defense and the expression of the retinoic signaling pathway in juvenile Seriola lalandi (Valenciennes, 1833)

Yellowtail kingfish (Seriola lalandi) is a valuable commercial aquacultural product in high demand in several countries. Growth performance, survival, lipid content, antioxidant enzyme system defense, gene expression and malformation were investigated in the juvenile specimens subjected to different diets. Three experimental diets with different proportions of fish oil (FO) and olive oil (OO) and different levels of long chain polyunsaturated fatty acids (LC PUFA), were formulated and manufactured: D1: 100% FO + 0% OO; D2: 50% FO + 50% OO; D3: 0% FO + 100% OO. S. lalandi juveniles weighing 0.81 g (57 days dph) were fed during four weeks with experimental diets (D1, D2, and D3). Samples of normal or malformed-jaw fish were collected at the end of the feeding trial. Although the incidence of malformations seemed to slightly increase with the incorporation of OO, the statistical association between diet and the malformation rate was not clear. The most frequent malformation observed was shortening of the lower jaw, followed by shortening of the upper jaw. At the gene expression level, the antioxidant genes CAT, SOD, GPX, RXR and PPAR were upregulated in malformed-jaw fish compared to normal specimens, independent of their diets. The results of multi-dimensional scaling suggest that a disruption of hepatic lipid composition may be associated with jaw and operculum malformations in juvenile S. lalandi.

FRI114 PUFAs Implicated In Platelet Activation Differ In Receptor Mediated Vs Post-receptor Insulin Resistance

Abstract Disclosure: R. Klein: None. S.T. Chung: None. R.J. Brown: None. Background: Severe insulin resistance (IR) can be classified as receptor mediated, in which all downstream signaling is blocked, or post receptor IR where some downstream signaling pathways are decreased and others are increased. Receptor-mediated IR occurs in rare mutations of the insulin receptor (INSR), whereas in most forms of IR, including type 2 diabetes (T2DM) and lipodystrophy (LD), IR is post-receptor. LD is a group of syndromes characterized by deficiency of fat depots leading to metabolic dysfunction similar to obesity. Patients with post-receptor IR have increased atherosclerotic cardiovascular disease (ASCVD) risk. Thrombosis underlies pathology of ASCVD and is a result of platelet (PLT) activation. Polyunsaturated fatty acids (PUFAs) are embedded in the PLT membrane and play a key role in thrombosis. During PLT activation, cytosolic phospholipase A2 (cPLA2) hydrolyzes membrane lipids, generating free PUFAs, leading to synthesis of mediators of blood vessel constriction, inflammation, and thrombosis. Methods: This was a cross-sectional study of subjects with INSR (N=30) and LD (N=30) matched for age, sex, HbA1c and pubertal stage. Untargeted metabolomic (848 compounds) and lipidomic (984 compounds) analysis was completed on serum after an 8-12 hour fast. Analyses were conducted by t-test and Mann-Whitney with adjustment for multiplicity. Bonferroni corrected P&amp;lt;0.05 was considered significant. Results: Of 19 long chain PUFAs (ω=3, ω=6) measured, 14 were significantly elevated in LD vs INSR, including arachidonate, docosahexaenoate, docosapentaenoate, stearidonate, and adrenate. There was no difference in linoleate, dihomo-linoleate, tetradecadienoate, linolenate, or docosadienoate levels between LD vs INSR. Among 8 long chain saturated FAs, only 3 were significantly higher in LD, 4 were comparable, and 1 was higher in INSR. All long and medium chain monounsaturated FAs were similar in LD vs INSR. cPLA2 was not different between LD and INSR. Conclusions: Our study shows that liberated PUFAs were higher in the patients with LD compared to INSR. A similar trend was not seen for other FFA such as saturated and monounsaturated FFA, suggesting that higher PUFAs in LD are unlikely to be caused by global differences in FFA metabolism, such as different peripheral uptake of FFA via lipoprotein lipase activity or diet. Instead, our data suggest an increase in PLT membrane ability to store and release PUFAs. These data suggest increased ASCVD risk in post-receptor insulin resistance may be partially mediated through differences in platelet activation. Presentation: Friday, June 16, 2023

Are Upwelling Systems an Underestimated Source of Long Chain Omega‐3 in the Ocean? The Case of the Southern Benguela Upwelling System

AbstractThe Benguela upwelling system (BUS) is one of the world's most productive ecosystems, supporting globally relevant fisheries. The BUS marine community is modulated by the availability of nutrients and omega‐3 long chain polyunsaturated fatty acid (hereafter, LC omega‐3). Phytoplankton growth in the BUS can be supported by upwelled nitrate, a new nitrogen (N) source to the surface, or by recycled N such as ammonium. Preferential assimilation of one N source over another may yield differences in LC omega‐3 production between high and low food‐quality species. To evaluate how upwelling and the N source(s) consumed by phytoplankton influence LC omega‐3 production, we sampled a BUS anchor station daily for 10 days. Upwelling on days 5–7 supplied high concentrations of nutrients to the surface, while pre‐ and post‐upwelling, surface waters were stratified and nutrient concentrations were low. LC omega‐3 and phytoplankton concentrations were near‐zero during upwelling, and elevated pre‐ and post‐upwelling. Throughout our sampling, nanoplankton (2.7–10 µm) dominated primary production (30–95%), relying mainly on nitrate to support their growth. Surface LC omega‐3 concentrations reached peaks of 215 and 175 µg L−1 pre‐ and post‐upwelling, up to 10 times higher than previous measurements from the BUS (&lt;5 µg L−1). Pre‐upwelling, non‐diatom trophic markers (18:1n − 9, 18:4n − 3, 18:5n − 3) were dominant, with a switch over just two days to diatom trophic markers post‐upwelling (16:1n − 7, 16:2n − 4, 16:2n − 7, 16:3n − 4, 16:4n − 1). This study reveals the key role of upwelling in promoting phytoplankton LC omega‐3 production, which is tightly coupled to the supply of new nitrate. Additionally, the high observed LC omega‐3 concentrations suggest that global LC omega‐3 production is underestimated.

Effects of dietary n-3 LC-PUFA levels on the growth, immunity, and lipid metabolism of freshwater carnivorous teleost largemouth bass (Micropterus salmoides) juveniles

The n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) play important roles in the normal growth and metabolism of fish . In order to explore the appropriate requiremnts of n-3 LC-PUFA in juvenile largemouth bass Micropterus salmoides, a freshwater carnivorous teleost, four isoproteic (50 %) and isolipidic (11 %) diets were formulated. The control diet used fish oil (FO) as the sole lipid source, and the other three diets used mixed vegetable oil as the main lipid source and supplemented with 0.50 %, 0.80 % and 1.10 % n-3 LC-PUFA, respectively. After the juvenile largemouth bass (initial weight 12.11 ± 0.01 g) fed with the four diets for 75 days, the growth, serum and heptic biochemical indices, as well as hepatic lipid metabolism were investigated. The results showed that the growth performance of 0.50 %-1.10 % groups were high that of control group; comparing to the 1.10 % group, high weight gain, specific growth rate and daily gain, as well as muscle hardness, chewiness and gumminess were detected in the 0.80 % group (P < 0.05). With the increase of dietary n-3 LC-PUFA levels, the serum biochemical indices (total cholesterol, triglyceride, and aspartate aminotransferase activity) and hepatic triglyceride were significantly decreased, while the serum acid phosphatase and alkaline phosphatase, as well as hepatic and muscle n-3 LC-PUFA contents were significantly increased (P < 0.05). Compared with the 0.50 % group, high hepatic mRNA expression levels of anti-inflammatory genes (il-10, tgf-β) were observed in the 0.80 % group (P < 0.05); and the relatively high transcript levels of genes related to lipid transport and catabolism (hsl, pparα, fatp and mtp) and low transcript levels of genes related to lipid anabolism (accα and pparγ) were detected in the 0.80 % and 1.10 % groups, as well as high mRNA levels of accα and pparγ were measured in the 0.80 % group (P < 0.05). The results indicated that 0.80 % dietary n-3 LC-PUFA level is suitable for largemouth bass concerning the growth performance, muscle quality and hepatic lipid metabolism. When subjected the weight gain to the second-order polynomial regression analysis, the maximum value was achieved at 0.76 % n-3 LC-PUFA level, which provide a basis for the development of formula feed for largemouth bass.

Dietary methylmercury and fatty acids affect the lipid metabolism of adipose tissue and liver in rainbow trout

Methylmercury (MeHg) is a pervasive environmental contaminant in aquatic ecosystems that can reach elevated concentrations in fish of high trophic levels, such as salmonids. The present study aims at investigating the individual and combined impacts of dietary MeHg and fatty acids on lipid metabolism in juvenile rainbow trout (Oncorhynchus mykiss) with a focus on two key organs, adipose tissue and liver. MeHg and fatty acids are both known to act on energy homeostasis although little is known about their interplay on lipid metabolism in fish. Fish were fed diets enriched in linoleic acid (LA, 18:2 n-6), α-linolenic acid (ALA, 18:3 n-3), eicosapentaenoic acid (EPA, 20:5 n-3) or docosahexaenoic acid (DHA, 22:6 n-3) for ten weeks, with the addition of MeHg to the diets during the last six weeks (0, 2.4 or 5.5 mg MeHg/kg dry matter). LA and ALA are polyunsaturated fatty acids (PUFA) typical of plant-derived oils whereas EPA and DHA are n-3 long chain PUFA largely found in fish oil, all used in feed formulation in aquaculture. The results showed that the LA-enriched diet induced a higher whole-body lipid content compared to the three other diets. On the contrary, the addition of MeHg led to a significant reduction of the whole-body lipid content, regardless of the diet. Interestingly, the adipocytes were larger both in presence of LA, compared to EPA and DHA, or MeHg, indicating a lipogenic effect of these two compounds. No effect was, however, observed on lipid accumulation per gram of adipose tissue. The fatty acid composition of adipose tissue and liver was significantly modified by the dietary lipids, reflecting both the fatty acid composition of the diets and the high bioconversion capacity of the rainbow trout. Exposure to MeHg selectively led to a release of n-6 PUFA from the hepatic membranes of fish fed the LA-enriched diet, showing a disruption of the pathways using n-6 PUFA. This study highlights the significant impact of MeHg exposure and dietary fatty acids on lipid metabolism in fish. Further investigation is needed to elucidate the underlying mechanisms and to explore the potential involvement of other organs.

Long Chain Polyunsaturated Fatty Acids and Their Role in COVID 19-associated Inflammation and Dysbiosis

The COVID-19 pandemic has been an on-going global health problem since it started more than three years ago. Efficient treatment and its emerging long-term effects remain unresolved. The primary cause of COVID-19 deaths is the excessive immune response resulting in a cytokine storm leading to eventual organ failure. Dysbiosis has been observed in patients infected with SARS-CoV-2, promoting further inflammation and increasing risks for long COVID. Most of the current treatments for COVID-19 including vaccines are directed against the virus and its replication. However, these treatments need to be administered before viral infection (in the case of vaccines) or early in the infection process. Moreover, these treatments do not address the inflammatory phase of the disease, where cytokine storm increases the risk of death or may be a significant contributor to long COVID. Omega-3 fatty acids which are components of cell membranes are known to be precursors of anti-inflammatory compounds and aid in the regulation of the human microbiome. This article presents a hypothesis that posits the role of long-chain polyunsaturated fatty acids in modulating COVID-19 inflammation via the regulation of the lung and gut microbiomes, which have been associated with the body's immune response to SARS-CoV-2 infection. With known safety and benefits of omega-3 fatty acids, supplementation may be effective in preventing severe COVID-19 symptoms, managing mild and moderate symptoms, and may even extend post-recovery to mitigate increased risk for cardiovascular diseases after SARS-CoV-2 infection and recovery.

A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant inherited disease characterized by age-related cerebellar degeneration and ataxia caused by mutations in the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. The ELOVL4 enzyme catalyzes the biosynthesis of both very long chain saturated fatty acids (VLC-SFA) and very long chain polyunsaturated fatty acids (VLC-PUFA) that are important for neuronal, reproductive, and skin function. Several variants in ELOVL4 have been shown to cause different tissue-specific disorders including SCA34 with or without Erythrokeratodermia Variabilis (EKV), a skin condition characterized by dry, scaly skin, Autosomal Dominant Stargardt-Like Macular Dystrophy (STGD3), and seizures associated with neuro-ichthyotic disorders. What is puzzling is how different mutations in the same gene seem to cause different tissue-specific disorders. To date, no SCA34 patients have presented with both SCA34 and STGD3 pathology that is caused by ELOVL4 variants that cause truncation of ELOVL4. Here, we report a novel case of an early childhood onset and rapidly progressive cerebellar degeneration and retinal dysfunction in a Belgian-Italian girl who developed severe dysarthria and gait problems starting at about 3.5 years of age and progressed to immobility by 4.5 years of age. Brain magnetic resonance imaging (MRI) revealed progressive vermian, cerebellar, cortical atrophy, progressive corpus callosum slimming, and hot cross bun sign visible on the MRI. Ophthalmological examinations also revealed progressive macular dysfunction as measured by electroretinography. Using exome sequencing, we identified a novel heterozygous ELOVL4 variant, c.503 T > C (p. L168S) in the patient. To understand the enzymatic function of this novel ELOVL4 variant and how it alters the levels of VLC-PUFA and VLC-SFA biosynthesis to contribute to cerebellar and retinal dysfunction, we expressed wild-type ELOVL4 or the L168S ELOVL4 variant in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. We showed that the L168S ELOVL4 variant is deficient in the biosynthesis of VLC-SFA and VLC-PUFA. Our work suggests that differential depletion of these fatty acids may be a contributing factor to the pathogenic mechanism of SCA34 with or without EKV. Further studies will help further define how the different ELOVL4 variants cause different tissue-specific disorders with variable ages of onset.

Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation.

To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice's kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific.

Exploring the use of fish as indicators of eicosapentaenoic and docosahexaenoic supply in lake ecosystems.

An adequate supply of food sources with high levels (i.e., weight proportion of total fatty acids) and contents (i.e., absolute amount per mass) of long chain polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are important for ecosystems. Therefore, the supply of EPA and DHA from basal food sources is a useful indicator of ecosystem health. To determine whether EPA and DHA levels and contents in fish can be used as indicators of EPA and DHA supply in lakes, five dominant species of fish and basal food sources (seston and sediment) were collected monthly from June to November from 2016 to 2021 from Lake Hachiro, Japan. Seston and Hypomesus nipponensis were collected from 12 lakes (one collection per lake) with varying seston contents in EPA and DHA. The trends of EPA and DHA in all fish species were similar to those of the basal food sources. Correlation analysis showed that the EPA levels were strongly correlated between fish and seston; moreover, the correlation coefficient increased when a 1- or 2-month moving average was applied to the basal food sources, suggesting that fish represent a time-integrated supply of EPA and DHA. EPA levels of H. nipponensis had the highest correlation coefficients with seston among all fish species. EPA levels of H. nipponensis were significantly correlated with those of seston among lakes. The results of this study suggest that H. nipponensis is a useful indicator of EPA and DHA supplies in lake ecosystems.

The impact of varying EPA:DHA ratio on Atlantic salmon health and welfare

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential fatty acids (EFA) vital for Atlantic salmon health, growth performance, and product quality. Yet, DHA and especially EPA are in short supply as ingredients for aquafeeds. Whilst the role of EFA in salmonid nutrition has been well studied, clear guidelines for aquaculture nutrition practitioners are still missing. This article addresses this gap by testing different EPA:DHA ratios (0.15, 0.55, and 0.98) when these two EFA represent at least 10% of the total pool of fatty acids in aquafeeds. Grow-out trials revealed no differences in zootechnical performance between fish fed the different diets during the initial eight weeks before vaccination challenge, nor on the subsequent three weeks post-vaccination for fish truly vaccinated or sham vaccinated (used as control groups for each of the three diets tested). Nonetheless, the FCR of vaccinated fish was significantly higher than sham vaccinated conspecifics, but diet yielded no significant effect. The expression of most genes screened (e.g., Elongation Factor 1α (Elf-1α), Interleukin 10 (IL10), Interleukin 8 (IL8), Tumor Necrosis Factor (TNFα)) was not significantly affected by vaccination or diet, while Viperine and Mx genes were upregulated in sham vaccinated fish fed the experimental diet with an EPA:DHA ratio of 0.55. The fatty acid composition of head kidney was affected by diet, namely EPA, but not DHA. The fatty acid profile of white muscle was also significantly affected by diet, with contrasting results for EPA and DHA; EPA content was higher for fish fed diets with higher EPA:DHA ratios and DHA levels were significantly higher (peaking at 16% of the total pool of fatty acids) when fish were provided with the diet featuring the lowest EPA:DHA ratio (0.15). Interestingly, fish fed the diet with the highest EPA:DHA ratio showed a lower number of wounded fish at the end of the grow-out period post-vaccination. Despite the reduction was not statistically significant, given the severe impact of wounded fish on salmon farming productivity, our results indicate that the partial replacement of fish oil with algal oil in salmon feed contributed to achieving a balanced EPA:DHA ratio, an adequate profile of Omega-3 long chain polyunsaturated fatty acids and improved the overall health and welfare of fish. This approach creates the opportunity to increase the productivity of fish farming operations and foster a more sustainable growth of the aquaculture industry.

Effects of Different Feeding Regimes on Growth Performance, Survival Rate, Carcass Composition, Fatty Acids Profile, and Digestive Enzyme Activities of Great Sturgeon (Huso huso Linnaeus, 1758) Larvae

Six different feeding regimes (FR) were tested from 7 to 38 days post hatching (dph). Five thousand four hundred larvae (7 dph, 0.048 g) were randomly stocked in 18 fiberglass tanks contained 100 L fresh water (300 larvae per each tank). In larvae fed with FR-B, includes Artemia nauplii (AN) + Artemia biomass (AB) + microdiet (MD), the body weight (BW) at the end of trail (38 dph) similar the FR-D (AN + CHL + AB + MD), and E (AN + CHL + AB), was at high level. Survival rate was higher in larvae fed FR-A includes AN + chironomid larvae (CHL) + MD, but had a lower BW ( p &lt; 0.05 ). Moderate BW and survival rate were detected in larvae fed FR-C (AN + DP + MD). Larvae fed only MD (FR-F), had the lowest survival and the highest BW ( p &lt; 0.05 ). Different FR had a significant effect on crude protein (CP), crude fat (CF), ash, and dry weight ( p &lt; 0.05 ). The larvae fed FR-C and D had the highest CP ( p &lt; 0.05 ). The highest CF and ash in larvae were detected in FR-F and C, respectively ( p &lt; 0.05 ). Larvae from FR-A and B had higher levels of n−3 long chain polyunsaturated fatty acids in comparison with others FR ( p &lt; 0.05 ). The use of AB and CHL can increased the weight and survival rate of larvae, respectively. At the end of trail, the activity of pepsin, trypsin, lipase and α-amylase enzyme levels were lower in FR-B and F than others FR. Totally, by using a combination of AN + CHL + AB + MD had better results than others and ordered to H. huso larvae feeding. Using MD alone, can cause lesser development of the digestive system and little attractiveness, therefore it can cause starvation, and the empty digestive tract of larvae.

Studi LCPUFA dan variant genetik enzim Fatty Acid Desaturase pada masa kehamilan di Asia masih langka

Enourmos body of literatures reported that inadequacy of LCPUFAS (long chain polyunsaturated fatty acids) during pregnancy is associated with premature birth and newborn low birth weight. LCPUFAs may modified pregnancy outcome by modulating blood fatty acid, lipid profile and apo-lipoprotein. Current study reviewed literatures that investigate the association between maternal LCPUFAS and genetic variant of FADS (fatty acid desaturares), which act on endogenous synthesis of omega 3 precursors, and birth outcome in Asian countries particularly Indonesia. Using accessed PUBMED and Google Scholar database during January 2015 to December 2022 with a query of LCPUFAs, FADS, pregnancy and birth outcome, there were nine peer-reviewed literatures in English and two local literatures. Current finding confirmed the scarcity of literatures that associating LCPUFAS, FADS during pregnancy and birth outcome in Asian countries particularly in Indonesia. The finding also highlighted the role of LCPUFAS in prolonged gestation and desirable birth outcome. Genetic variant of FADS was indicated to modify the association of maternal LCPUFAs and birth ouctome. The scarcity of literaturs encourages other researcher to conduct further investigatation on this topic

The Influence of Lipid Microdomain Heterogeneity on Protein-Protein Interactions: Proteomic Analysis of Co-Immunoprecipitated Binding Partners of P450 1A2 and P450 3A in Rat Liver Microsomes.

Liver cytochrome P450s (CYPs) of the endoplasmic reticulum (ER) are involved in the metabolism of exogenous and endogenous chemicals. The ER is not uniform, but possesses ordered lipid microdomains containing higher levels of saturated fatty acids, sphingomyelin, and cholesterol and disordered regions containing higher levels of polyunsaturated fatty acid chains. The various forms of drug-metabolizing P450s partition to either the ordered or disordered lipid microdomains with different degrees of specificity. P450s readily form complexes with ER-resident proteins, including other forms of P450. This study aims to ascertain whether lipid microdomain localization influences protein-P450 interactions in rat liver microsomes. Thus, liver microsomes were co-immunoprecipitated with CYP1A2-specific and CYP3A-specific antibodies, and the co-immunoprecipitating proteins were identified by liquid chromatography mass spectrometry proteomic analysis. These two P450s preferentially partition to ordered and disordered microdomains, respectively. More than 100 proteins were co-immunoprecipitated with each P450. Segregation of proteins into different microdomains did not preclude their interaction. However, CYP3A interacted broadly with proteins from ordered microdomains, whereas CYP1A2 reacted with a limited subset of these proteins. This is consistent with the concept of lipid raft heterogeneity and may indicate that CYP1A2 is targeted to a specific type of lipid raft. Although many of the interacting proteins for both P450s were other-drug metabolizing enzymes, other interactions were also evident. The consistent CYP3A binding partners were predominantly involved in phase I/II drug metabolism; however, CYP1A2 interacted not only with xenobiotic metabolizing enzymes, but also with enzymes involved in diverse cellular responses such as ER stress and protein folding. SIGNIFICANCE STATEMENT: This work describes the protein interactomes in rat liver microsomes of two important cytochromes P450s (CYP1A2 and CYP3A) in drug metabolism and describes the relationship of the interacting proteins to lipid microdomain distribution.

Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.

Oxylipin secretion by human CD3+ T lymphocytes in vitro is modified by the exogenous essential fatty acid ratio and life stage.

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation. A number of PUFAs are precursors to oxylipins, including the essential fatty acids (EFAs) linoleic acid (LA) and α-linolenic acid (ALA). LA and ALA are also substrates for synthesis of longer chain PUFAs. Studies with stable isotopes have shown that the relative amounts of LA and ALA can influence their partitioning by T lymphocytes between conversion to longer chain PUFAs and to oxylipins. It is not known whether the relative availability of EFA substrates influences the overall pattern of oxylipin secretion by human T cells or if this changes across the life stages. To address this, the oxylipin profile was determined in supernatants from resting and mitogen activated human CD3+ T cell cultures incubated in medium containing an EFA ratio of either 5:1 or 8:1 (LA : ALA). Furthermore, oxylipin profiles in supernatants of T cells from three life stages, namely fetal (derived from umbilical cord blood), adults and seniors, treated with the 5:1 EFA ratio were determined. The extracellular oxylipin profiles were affected more by the EFA ratio than mitogen stimulation such that n-3 PUFA-derived oxylipin concentrations were higher with the 5:1 EFA ratio than the 8:1 ratio, possibly due to PUFA precursor competition for lipoxygenases. 47 oxylipin species were measured in all cell culture supernatants. Extracellular oxylipin concentrations were generally higher for fetal T cells than for T cells from adult and senior donors, although the composition of oxylipins was similar across the life stages. The contribution of oxylipins towards an immunological phenotype might be due to the capacity of T cells to synthesize oxylipins rather than the nature of the oxylipins produced.