Ω3 Polyunsaturated Fatty Acids Research Articles

Engineering Nannochloropsis oceanica for concurrent production of canthaxanthin and eicosapentaenoic acid

The marine alga Nannochloropsis oceanica can synthesize the high-value ketocarotenoid canthaxanthin yet at an extremely low level. Introducing a β-carotenoid ketolase from Chlamydomonas reinhardtii into the chloroplast for expression, enabled N. oceanica to synthesize substantial amounts of canthaxanthin and grow better under high light. Compared to wild type, the engineered strain had higher levels of primary carotenoids and chlorophyll a as well, and synthesized more eicosapentaenoic acid (EPA, an ω3 polyunsaturated fatty acids). Further metabolic engineering by enhancing the flux to carotenoids or suppressing competing pathways allowed for a considerable increase of canthaxanthin, reaching 4.7 mg g−1 dry weight. A fed-batch culture strategy with nitrate and phosphate replenishment was developed for the co-production of canthaxanthin and EPA, which within a 10-day period reached 37.6 and 268.8 mg/L, respectively. This study sheds light on manipulating the industrially relevant alga for efficient co-production of high-value biochemicals from CO2.

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.

Microfluidic-Derived Docosahexaenoic Acid Liposomes for Targeting Glioblastoma and Its Inflammatory Microenvironment.

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by limited treatment options and a poor prognosis. Its aggressiveness is attributed not only to the uncontrolled proliferation and invasion of tumor cells but also to the complex interplay between these cells and the surrounding microenvironment. Within the tumor microenvironment, an intricate network of immune cells, stromal cells, and various signaling molecules creates a pro-inflammatory milieu that supports tumor growth and progression. Docosahexaenoic acid (DHA), an essential ω3 polyunsaturated fatty acid for brain function, is associated with anti-inflammatory and anticarcinogenic properties. Therefore, in this work, DHA liposomes were synthesized using a microfluidic platform to target and reduce the inflammatory environment of GBM. The liposomes were rapidly taken up by macrophages in a time-dependent manner without causing cytotoxicity. Moreover, DHA liposomes successfully downregulated the expression of inflammatory-associated genes (IL-6; IL-1β; TNFα; NF-κB, and STAT-1) and the secretion of key cytokines (IL-6 and TNFα) in stimulated macrophages and GBM cells. Conversely, no significant differences were observed in the expression of IL-10, an anti-inflammatory gene expressed in alternatively activated macrophages. Additionally, DHA liposomes were found to be more efficient in regulating the inflammatory profile of these cells compared with a free formulation of DHA. The nanomedicine platform established in this work opens new opportunities for developing liposomes incorporating DHA to target GBM and its inflammatory milieu.

Molecular cloning and functional analysis of a plastidial ω3 desaturase from Emiliania huxleyi.

Emiliania huxleyi is a marine microalga playing a significant ecological and biogeochemical role in oceans. It can produce several polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA, 22:6-4,7,10,13,16,19) and octadecapentaenoic acid (OPA, 18:5-3,6,9,12,15), providing a primary source for nutritionally important ω3 PUFAs in the marine food chain. However, the biosynthesis of these PUFAs in this organism is not well understood. In this study, a full length plastidial ω3 desaturase cDNA (EhN3) was cloned from this alga. Heterologous expression of EhN3 with and without the chloroplast targeting peptide (cTP) in cyanobacterium Synechococcus elongatus showed that it possessed high desaturation activity toward C18-ω6 PUFAs, linoleic acid (LA, 18:2-9,12), γ-linolenic acid (GLA, 18:3-6,9,12), and C20-ω6 PUFAs, dihomo-γ-linolenic acid (DGLA, 20:3-8,11,14) and arachidonic acid (ARA, 20:4-5,8,11,14) that were exogenously supplied. Desaturation efficiency could reach almost 100% in a time course. On the other hand, when expressed in Saccharomyces cerevisiae, EhN3 with and without cTP did not exhibit any activity. Lipid analysis of Synechococcus transformants expressing EhN3 showed that it utilized galactolipids as substrates. Transcriptional expression analysis revealed that the expression of the gene increased while the growth temperature decreased, which was correlated with the increased production of ω3-PUFAs, particularly OPA. This is the first report of a plastidial ω3 desaturase from microalgae that can effectively introduce an ω3 double bond into both C18-ω6 and C20-ω6 PUFAs. EhN3 might also be one of the key enzymes involved in the biosynthesis of OPA in E. huxleyi through the plastidial aerobic pathway.

Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.

We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.g lipoxygenase, cytochrome p450, or cyclooxygenase (COX)) which mediate intracellular adaptive signaling. Plasma phospholipid PUFA abundance at Exam 1 as mass percent EPA, DHA, and arachidonic acid (AA) from the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using pathway modeling to determine the association with time-dependent changes in left ventricular (LV) mass (LVM), end-diastolic LV volume (EDV), and end-systolic volume (ESV) measured by cardiac MRI at Exams 1 and 5. Ejection fraction (EF) and mass:volume (MV) were calculated posteriorly from the first three. 2,877 subjects had available MRI data. Participants with low AA and EPA had accelerated age-dependent declines in LVM. Males with low AA and EPA also had accelerated declines in EDV, but among females there was no PUFA association with EDV declines and exam 5 EDV status was positively associated with AA. Both sexes had nearly the same positive association of AA with changes in ESV. Plasma phospholipid AA and EPA are prospectively associated with indices of heart remodeling, including ventricular remodeling and performance. Combined AA and EPA scarcity was associated with the most accelerated age-related changes and exam 5 status, while the greatest benefits were found among participants with both PUFAs. This suggests that both PUFAs are required for optimal slowing of age-related declines in ventricular function.

Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke

Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p=0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p=0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p=0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p<0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p=0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p=0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient-1.316, 95% CI -2.290∼-0.342, p=0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p=0.021). Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

Dietary fatty acids modulate oxidative stress response to air pollution but not to infection.

Anthropogenic changes to the environment expose wildlife to many pollutants. Among these, tropospheric ozone is of global concern and a highly potent pro-oxidant. In addition, human activities include several other implications for wildlife, e.g., changed food availability and changed distribution of pathogens in cities. These co-occurring habitat changes may interact, thereby modulating the physiological responses and costs related to anthropogenic change. For instance, many food items associated with humans (e.g., food waste and feeders for wild birds) contain relatively more ω6-than ω3-polyunsaturated fatty acids (PUFAs). Metabolites derived from ω6-PUFAs can enhance inflammation and oxidative stress towards a stimulus, whereas the opposite response is linked to ω3-derived metabolites. Hence, we hypothesized that differential intake of ω6-and ω3-PUFAs modulates the oxidative stress state of birds and thereby affects the responses towards pro-oxidants. To test this, we manipulated dietary ω6:ω3 ratios and ozone levels in a full-factorial experiment using captive zebra finches (Taeniopygia guttata). Additionally, we simulated an infection, thereby also triggering the immune system's adaptive pro-oxidant release (i.e., oxidative burst), by injecting lipopolysaccharide. Under normal air conditions, the ω3-diet birds had a lower antioxidant ratio (GSH/GSSG ratio) compared to the ω6-diet birds. When exposed to ozone, however, the diet effect disappeared. Instead, ozone exposure overall reduced the total concentration of the key antioxidant glutathione (tGSH). Moreover, the birds on the ω6-rich diet had an overall higher antioxidant capacity (OXY) compared to birds fed a ω3-rich diet. Interestingly, only the immune challenge increased oxidative damage, suggesting the oxidative burst of the immune system overrides the other pro-oxidative processes, including diet. Taken together, our results show that ozone, dietary PUFAs, and infection all affect the redox-system, but in different ways, suggesting that the underlying responses are decoupled despite that they all increase pro-oxidant exposure or generation. Despite lack of apparent cumulative effect in the independent biomarkers, the combined single effects could together reduce overall cellular functioning and efficiency over time in wild birds exposed to pathogens, ozone, and anthropogenic food sources.

Effects of temperature up-shift and UV-A radiation on fatty acids content and expression of desaturase genes in cyanobacteria Microcystis aeruginosa: stress tolerance and acclimation responses.

Temperature up-shift and UV-A radiation effects on growth, lipid damage, fatty acid (FA) composition and expression of desaturase genes desA and desB were investigated in the cyanobacteria Microcystis aeruginosa. Although UV-A damaging effect has been well documented, reports on the interactive effects of UV radiation exposure and warming on cyanobacteria are scarce. Temperature and UV-A doses were selected based on the physiological responses previously obtained by studies with the same M. aeruginosa strain used in this study. Cells pre-grown at 26°C were incubated at the same temperature or 29°C and exposed to UV-A + PAR and only PAR for 9days. Growth rate was significantly affected by UV-A radiation independently of the temperature throughout the experiment. High temperature produced lipid damage significantly higher throughout the experiment, decreasing at day 9 as compared to 26°C. In addition, the cells grown at 29°C under UV-A displayed a decrease in polyunsaturated FA (PUFA) levels, with ω3 PUFA being mostly affected at the end of exposure. Previously, we reported that UV-A-induced lipid damage affects differentially ω3 and ω6 PUFAs. We report that UV-A radiation leads to an upregulation of desA, possibly due to lipid damage. In addition, the temperature up-shift upregulates desA and desB regardless of the radiation. The lack of lipid damage for UV-A on ω3 could explain the lack of transcription induction of desB. The significant ω6 decrease at 26°C in cells exposed to UV-A could be due to the lack of upregulation of desA.

Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration.

Gene and lncRNA Profiling of ω3/ω6 Polyunsaturated Fatty Acid-Exposed Human Visceral Adipocytes Uncovers Different Responses in Healthy Lean, Obese and Colorectal Cancer-Affected Individuals.

Colorectal cancer (CRC) is a major life-threatening disease, being the third most common cancer and a leading cause of death worldwide. Enhanced adiposity, particularly visceral fat, is a major risk factor for CRC, and obesity-associated alterations in metabolic, inflammatory and immune profiles in visceral adipose tissue (VAT) strongly contribute to promoting or sustaining intestinal carcinogenesis. The role of diet and nutrition in obesity and CRC has been extensively demonstrated, and AT represents the main place where diet-induced signals are integrated. Among the factors introduced with diet and processed or enriched in AT, ω3/ω6 polyunsaturated fatty acids (PUFAs) are endowed with pro- or anti-inflammatory properties and have been shown to exert either promoting or protective roles in CRC. In this study, we investigated the impact of ex vivo exposure to the ω3 and ω6 PUFAs docosahexaenoic and arachidonic acids on VAT adipocyte whole transcription in healthy lean, obese and CRC-affected individuals. High-throughput sequencing of protein-coding and long non-coding RNAs allowed us to identify specific pathways and regulatory circuits controlled by PUFAs and highlighted an impaired responsiveness of obese and CRC-affected individuals as compared to the strong response observed in healthy lean subjects. This further supports the role of healthy diets and balanced ω3/ω6 PUFA intake in the primary prevention of obesity and cancer.

Enhancing the quality and technological properties of goose meat during low-temperature storage through the action of biologically active substances from oats and alfalfa

Poultry meat plays a key role as a source of high-quality protein, vitamins, minerals, and unsaturated fatty acids. However, unsaturated fatty acids, especially essential ones, are prone to oxidative reactions during meat storage, which can negatively affect its quality. The object of the study is the technology of obtaining and storing poultry meat. Legart Danish geese were used as the experimental material. Oats (Avena Sativa) and alfalfa (Medicago sativa) contain a large number of biologically active substances (minerals, unsaturated fatty acids, amino acids, antioxidants). Adding vegetative parts of oats and alfalfa to the diet of geese contributes to improving the quality of the obtained meat, especially after prolonged low-temperature storage. The geese were slaughtered on the 63rd day. The meat was stored at a temperature of –18 °C for 90 days. It was found that there was an 11.5 % increase in the live weight of the geese at an early slaughter age, an increase in protein content (by 5 %), better moisture-binding capacity (by 6–7.3 %), and a decrease in the content of lipid peroxidation products, especially on the 67th day of storage (28.3 %). There was a significant increase in the content of ω3 and ω6 polyunsaturated fatty acids (by 24.2 % and 10.8 %, respectively). There was an increase in the content of vitamin E and β-carotene, both before freezing (38.5 % and 19.6 %) and at the end of the storage period (50.9 % and 20 %). A tendency to increase the content of essential amino acids (threonine and methionine) was found. The results can be used in the production of goose meat to improve its nutritional characteristics, which is important for the health of consumers, meat producers, and also in scientific research on the development of technologies in the field of meat production and storage

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as analternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Roles of Nutrients in the Brain Development, Cognitive Function, and Mood of Dogs and Cats.

The brain is the central commander of all physical activities and the expression of emotions in animals. Its development and cognitive health critically depend on the neural network that consists of neurons, glial cells (namely, non-neuronal cells), and neurotransmitters (communicators between neurons). The latter include proteinogenic amino acids (e.g., L-glutamate, L-aspartate, and glycine) and their metabolites [e.g., γ-aminobutyrate, D-aspartate, D-serine, nitric oxide, carbon monoxide, hydrogen sulfide, and monoamines (e.g., dopamine, norepinephrine, epinephrine, and serotonin)]. In addition, some non-neurotransmitter metabolites of amino acids, such as taurine, creatine, and carnosine, also play important roles in brain development, cognitive health, behavior, and mood of dogs and cats. Much evidence shows that cats require dietary ω3 (α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid) and ω6 (linoleic acid and arachidonic acid) polyunsaturated fatty acids for the development of the central nervous system. As an essential component of membranes of neurons and glial cells, cholesterol is also crucial for cognitive development and function. In addition, vitamins and minerals are required for the metabolism of AAs, lipids, and glucose in the nervous system, and also act as antioxidants. Thus, inadequate nutrition will lead to mood disorders. Some amino acids (e.g., arginine, glycine, methionine, serine, taurine, tryptophan, and tyrosine) can help to alleviate behavioral and mood disorders (e.g., depression, anxiety and aggression). As abundant providers of all these functional amino acids and lipids, animal-sourced foods (e.g., liver, intestinal mucosa, and meat) play important roles in brain development, cognitive function, and mood of dogs and cats. This may explain, in part, why dogs and cats prefer to eat visceral organs of their prey. Adequate provision of nutrients in all phases of the life cycle (pregnancy, lactation, postnatal growth, and adulthood) is essential for optimizing neurological health, while preventing cognitive dysfunction and abnormal behavior.

A Genome-Wide Interaction Study of Erythrocyte ω-3 Polyunsaturated Fatty Acid Species and Memory in the Framingham Heart Study Offspring Cohort

BackgroundCognitive decline, and more specifically Alzheimer’s disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids. ObjectivesWe aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual’s genetically conferred risk of cognitive decline. MethodsThe Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness). ResultsOur analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits. ConclusionsIn this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

Omega-3 PUFA and the fitness and cognition of the nematode Caenorhabditis elegans under different environmental conditions

Many invertebrate species possess the metabolic ability to synthesize long-chain ω3 polyunsaturated fatty acids (PUFA) de novo. Due to their diverse effects on membrane architecture, neuroplasticity, growth and reproduction, PUFA have a high potential to positively influence the fitness of an organism. But how and when do these supposed advantages actually come into play? Other species, that are often closely related, pass natural selection without this special metabolic ability. The ω3-PUFA rich model organism Caenorhabditis elegans (Nematoda) and its mutant fat-1(wa9), lacking these PUFA, are a suitable test system. We analyzed potential impairments in reproduction and growth in a soil assay. Further, chemotaxis after aversive olfactory, associative learning and integration of a second sensory signal were assessed on agar plates. Moreover, we analyzed the phospholipid pattern of both C. elegans strains and further free-living nematodes species at different temperatures. While the phenotypic effects were rather small under standard conditions, lowering the temperature to 15 or even 10 °C or reducing the soil moisture, led to significant limitations, with the investigated parameters for neuroplasticity being most impaired. The ω3-PUFA free C. elegans mutant strain fat-1 did not adapt the fatty acid composition of its phospholipids to a decreasing temperature, while ω3-PUFA containing nematodes proportionally increased this PUFA group. In contrats, other ω3-PUFA free nematode species produced significantly more ω6-PUFA. Thus, the ability to synthesize long-chain ω3-PUFA de novo likely is fundamental for an increase in neuroplasticity and an efficient way for regulating membrane fluidity to maintain their functionality.

Chlorella pyrenoidosa mitigated the negative effect of cylindrospermopsin-producing and non-cylindrospermopsin-producing Raphidiopsis raciborskii on Daphnia magna as a dietary supplement.

Feeding effects are crucial for evaluating the capacity of zooplankton to regulate phytoplankton populations within freshwater ecosystems. To examine the impact of the bloom-forming cyanobacteria Raphidiopsis raciborskii, which occurs in tropical and subtropical freshwaters, on the growth of zooplankton Daphnia in relation to toxins, filament length and fatty acid content, we fed D. magna with R. raciborskii only (cylindrospermopsin (CYN)-producing and non-CYN-producing, as the negative controls), Chlorella pyrenoidosa only (as the positive control) and a mixed diet containing R. raciborskii (CYN-producing and non-CYN-producing) and C. pyrenoidosa. Consequently, our findings revealed that the toxic effect of CYN-producing R. raciborskii strains on Daphnia was mitigated by the coexistence of C. pyrenoidosa containing stearidonic acid (SDA, C18:4 ω3) in mixed diets. This was evident in the elevated survival rate compared that from diets containing only R. raciborskii and a significantly higher reproduction and population intrinsic increase rate compared to diets consisting of only R. raciborskii or C. pyrenoidos. Additionally, a strong positive correlation was observed between arachidonic acid (ARA, 20:4ω6) and the population intrinsic increase rate of Daphnia; notably, R. raciborskii strains were found to be rich in the ω6 polyunsaturated fatty acid ARA. These outcomes reinforce the crucial role of polyunsaturated fatty acids in predicting the population increase of crustacean zooplankton, which has long been neglected. Furthermore, our results underscore the potential effectiveness of zooplankton, particularly in temperate lakes, in controlling CYN-producing R. raciborskii populations.

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial

BackgroundDepressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. MethodsA total of 71 adolescents with depression (aged 13–24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. ResultsSignificant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LimitationsThe trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. ConclusionsOur results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Effects of microbial-converted ancient permafrost organic carbon on the growth and reproduction of Daphnia magna.

Immense amounts of ancient (radiocarbon age over 200years) organic carbon (OC) from permafrost are released into aquatic systems. Ancient terrestrial OC exists in numerous aquatic ecosystems. It has been reported that ancient OC can be incorporated by consumers in aquatic ecosystems, but the effect of ancient OC on the growth of consumers has rarely been studied. In this study, we extracted ancient dissolved organic carbon (DOC) from frozen soils in an alpine lake catchment. After a 6-day microbial conversion period, the contents of ω3 and ω6 polyunsaturated fatty acids (PUFAs) in ancient DOC increased. Proteobacteria and Actinobacteria were the primary taxa consuming the permafrost DOC and generating fatty acids. In addition to the exclusive diet of soil DOC (containing bacteria) or Chlorella pyrenoidosa, mixed diets of Chlorella pyrenoidosa, and ancient DOC (containing bacteria) in ratios of 2:1, 1:1, and 1:2 (by carbon concentration) were used to feed Daphnia magna. We discovered that Daphnia reared on the mixture with the DOC:Chlorella ratio of 1:2 had the highest contents of ω3 PUFAs and FAs. Daphnia reared exclusively on Chlorella and the mixture with the DOC:Chlorella ratio of 1:2 had the largest body size (3.1-3.4mm) and the highest offspring production (95.5-96.2 ind-1). Daphnia fed on mixed diets exhibited higher intrinsic rates of population growth (0.48-0.53 d-1) compared to those fed exclusively on Chlorella pyrenoidosa, or ancient DOC plus bacteria. Overall, ancient soil OC converted by bacteria can act as a valuable supplement to algae food to promote Daphnia growth.

Multi‐omic network analysis identified betacellulin as a novel target of omega‐3 fatty acid attenuation of western diet‐induced nonalcoholic steatohepatitis

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi‐omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta‐analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR‐binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor–β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti‐inflammatory and anti‐fibrotic effects of ω3 PUFA on NASH.

Time course of western diet (WD) induced nonalcoholic steatohepatitis (NASH) in female and male Ldlr-/- mice.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identification of factors contributing to the onset and progression of NAFLD have the potential to direct novel strategies to combat NAFLD. We examined the time course of western diet (WD)-induced NAFLD and its progression to nonalcoholic steatohepatitis (NASH) in age-matched female and male Ldlr-/- mice, with time-points at 1, 4, 8, 20 and 40 weeks on the WD. Controls included Ldlr-/- mice maintained on a purified low-fat diet (LFD) for 1 and 40 weeks. The approach included quantitation of anthropometric, plasma and liver markers of disease, plus hepatic histology, lipids, oxylipins, gene expression and selected metabolites. One week of feeding the WD caused a significant reduction in hepatic essential fatty acids (EFAs: 18:2, ω6, 18:3, ω3) which preceded the decline in many C20-22 ω3 and ω6 polyunsaturated fatty acids (PUFA) and PUFA-derived oxylipins after 4 weeks on the WD. In addition, expression of hepatic inflammation markers (CD40, CD44, Mcp1, Nlrp3, TLR2, TLR4, Trem2) increased significantly in both female & male mice after one week on the WD. These markers continued to increase over the 40-week WD feeding study. WD effects on hepatic EFA and inflammation preceded all significant WD-induced changes in body weight, insulin resistance (HOMA-IR), oxidative stress status (GSH/GSSG ratio) and histological and gene expression markers of macrosteatosis, extracellular matrix remodeling and fibrosis. Our findings establish that feeding Ldlr-/- mice the WD rapidly lowered hepatic EFAs and induced key inflammatory markers linked to NASH. Since EFAs have an established role in inflammation and hepatic inflammation plays a major role in NASH, we suggest that early clinical assessment of EFA status and correcting EFA deficiencies may be useful in reducing NASH severity.