Can essential fatty acids (EFAs) prevent and ameliorate post-COVID-19 long haul manifestations?

It is hypothesized that COVID-19, post-COVID and post-mRNA COVID-19 (and other related) vaccine manifestations including "long haul syndrome" are due to deficiency of essential fatty acids (EFAs) and dysregulation of their metabolism. This proposal is based on the observation that EFAs and their metabolites can modulate the swift immunostimulatory response of SARS-CoV-2 and similar enveloped viruses, suppress inappropriate cytokine release, possess cytoprotective action, modulate serotonin and bradykinin production and other neurotransmitters, inhibit NF-kB activation, regulate cGAS-STING pathway, modulate gut microbiota, inhibit platelet activation, regulate macrophage and leukocyte function, enhance wound healing and facilitate tissue regeneration and restore homeostasis. This implies that administration of EFAs could be of benefit in the prevention and management of COVID-19 and its associated complications.

The Dysregulation of Essential Fatty Acid (EFA) Metabolism May Be a Factor in the Pathogenesis of Sepsis.

I propose that a deficiency of essential fatty acids (EFAs) and an alteration in their (EFAs) metabolism could be a major factor in the pathogenesis of sepsis and sepsis-related mortality. The failure of corticosteroids, anti-TNF-α, and anti-interleukin-6 monoclonal antibodies can be attributed to this altered EFA metabolism in sepsis. Vitamin C; folic acid; and vitamin B1, B6, and B12 serve as co-factors necessary for the activity of desaturase enzymes that are the rate-limiting steps in the metabolism of EFAs. The altered metabolism of EFAs results in an imbalance in the production and activities of pro- and anti-inflammatory eicosanoids and cytokines resulting in both hyperimmune and hypoimmune responses seen in sepsis. This implies that restoring the metabolism of EFAs to normal may form a newer therapeutic approach both in the prevention and management of sepsis and other critical illnesses.

The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide.

Cystic fibrosis (CF) is the most common autosomal-recessive disease in Caucasians caused by mutations in the CF transmembrane regulator (CFTR) gene. Patients are usually diagnosed in infancy and are burdened with extensive medical treatments throughout their lives. One of the first documented biochemical defects in CF, which predates the cloning of CFTR gene for almost three decades, is an imbalance in the levels of polyunsaturated fatty acids (PUFAs). The principal hallmarks of this imbalance are increased levels of arachidonic acid and decreased levels of docosahexaenoic acids (DHA) in CF. This pro-inflammatory profile of PUFAs is an important component of sterile inflammation in CF, which is known to be detrimental, rather than protective for the patients. Despite decades of intensive research, the mechanistic basis of this phenomenon remains unclear. In this review we summarized the current knowledge on the biochemistry of PUFAs, with a focus on the metabolism of AA and DHA in CF. Finally, a synthetic retinoid called fenretinide (N-(4-hydroxy-phenyl) retinamide) was shown to be able to correct the pro-inflammatory imbalance of PUFAs in CF. Therefore, its pharmacological actions and clinical potential are briefly discussed as well.

Supplementation with alpha-linolenic acid and inflammation: a feasibility trial.

Consumption of omega-3 fatty acids, including the precursor α-linolenic acid (ALA) is often sub-optimal and not in line with international guidelines. Supplementation is debatable, but some individuals, e.g., pre-diabetic, low-grade inflammation, cardiometabolic yet otherwise healthy subjects, might benefit from supra-physiological omega-3 intake, particularly to lessen inflammation. We explored the feasibility of a large clinical trial by performing a pilot study to evaluate adherence, palatability, and self-reported side effects of ALA administration in a group of volunteers. We enrolled 12 individuals with borderline dyslipidemia or overweight, treated with dietary advice according to international guidelines and who had insufficient intakes of essential fatty acids. Subjects were followed for nutritional counselling and were matched with appropriate controls. Patients were administered 6 g/day of ALA, for two months. We report the absence of side effects. such as fishy aftertaste and gastrointestinal distress, in addition to a slight decrease of C-reactive protein concentrations (Identifier: ISRCTN13118704).

Bioactive Lipids in Age-Related Disorders.

Our own studies and those of others have shown that defects in essential fatty acid (EFA) metabolism occurs in age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, immune dysfunction and cancer. It has been noted that in all these disorders there could occur a defect in the activities of desaturases, cyclo-oxygenase (COX), and lipoxygenase (LOX) enzymes leading to a decrease in the formation of their long-chain products gamma-linolenic acid (GLA), arachidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). This leads to an increase in the production of pro-inflammatory prostaglandin E2 (PGE2), thromboxanes (TXs), and leukotrienes (LTs) and a decrease in anti-inflammatory lipoxin A4, resolvins, protectins and maresins. All these bioactive molecules are termed as bioactive lipids (BALs). This imbalance in the metabolites of EFAs leads to low-grade systemic inflammation and at times acute inflammatory events at specific local sites that trigger the development of various age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, coronary heart disease, atherosclerosis, and immune dysfunction as seen in rheumatoid arthritis, lupus, nephritis and other localized inflammatory conditions. This evidence implies that methods designed to restore BALs to normal can prevent age-related disorders and enhance longevity and health.

Patatin-like phospholipase domain­containing protein 3 promotes transfer of essential fatty acids from triglycerides to phospholipids in hepatic lipid droplets.

Fatty liver disease (FLD) is a burgeoning health problem. A missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) confers susceptibility to FLD, although the mechanism is not known. To glean first insights into the physiological function of PNPLA3, we performed detailed lipidomic profiling of liver lysates and lipid droplets (LDs) from WT and Pnpla3-/- (KO) mice and from knock-in (ki) mice expressing either the 148M variant (IM-ki mice) or a variant (S47A) that renders the protein catalytically inactive (SA-ki mice). The four strains differed in composition of very-long-chain polyunsaturated fatty acids (vLCPUFA) in hepatic LDs. In the LDs of IM-ki mice, vLCPUFAs were depleted from triglycerides and enriched in phospholipids. Conversely, vLCPUFAs were enriched in triglycerides and depleted from phospholipids in SA-ki and Pnpla3-/- mice. Release of vLCPUFAs from hepatic LDs incubated ex vivo was increased in droplets from IM-ki mice and decreased from droplets isolated from Pnpla3-/- and SA-ki mice relative to those of WT mice. Thus, the physiological role of PNPLA3 appears to be to remodel triglycerides and phospholipids in LDs, perhaps to accommodate changes in LD size in response to feeding. Because SA-ki and IM-ki both cause FLD and yet have opposite effects on the lipidomic profile of LDs, we conclude that the FLD associated with genetic variation in PNPLA3 is not related to the enzyme's role in remodeling LD lipids.

Immunoresolvents in asthma and allergic diseases: Review and update.

Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.

Hemp (Marijuana) reverted Copper-induced toxic effects on the essential fatty acid profile of Labeo rohita and Cirrhinus mrigala.

Heavy metals pollution affects the nutritive value of fish. This study examined if the inclusion of dietary hempseed (HS) and hempseed oil (HO) in the diet of the fish could revert the copper-induced toxic effects on muscle fatty acid profile of rohu (Labeo rohita) and mrigal (Cirrhinus mrigala). Fingerlings of both species were exposed to a sub-lethal concentration of copper i.e., 20% of LC50 (1.34 ppm for rohu and 1.52 ppm for mrigal) for 96 h for 30 days. Following exposure, fish were maintained on graded levels of HO (1, 2 and 3%) or on HS (5, 10 and 15%) for 50 days. Copper exposure showed a significant effect on the fatty acid composition of both species; increased their saturated (SFA) to unsaturated (USFA) and altered their omega-3/omega-6 (ω-3/ω-6) ratios. However, feeding graded levels of hempseed products reverted the toxic effects of copper on the fatty acid profile of both the species, significantly increased muscle total fatty acid contents, improved ω-3/ω-6 ratios, and decreased SFA / USFA ratio in % inclusion dependent manner. Furthermore, hempseed product showed a species-specific effect on USFA. The ω-3/ω-6 ratios decreased in the muscle of C. mrigala whereas an increasing trend with an increase in hempseed product % inclusion was observed in L. rohita. Moreover, HS showed a higher impact on both species as compared to HO. With the findings of this study, hempseed product could be recommended as a feed ingredient for enhancing the essential fatty acid contents of fish which in turn can have a good impact on consumer health.

A cross-sectional study of fatty acids and brain-derived neurotrophic factor (BDNF) in human milk from lactating women following vegan, vegetarian, and omnivore diets.

PURPOSE: Essential fatty acids are critical for brain growth and neurodevelopment in infancy. Maternal diet and supplement use have a significant impact on the fat composition of human milk. The objective of this study is to assess supplement utilization patterns and fatty acid and brain-derived neurotrophic factor (BDNF) concentrations in the breast milk of women following vegan, vegetarian, and omnivore diet patterns. METHODS: This is a cross-sectional, observational study of 74 lactating women in the United States following a vegan (n = 26), vegetarian (n = 22), or omnivore (n = 26) diet pattern. A single breast milk sample was collected from each participant and assessed for fatty acids and BDNF. RESULTS: Median unsaturated fatty acids in the breast milk of vegan, vegetarian, and omnivores, as a percentage of total fatty acids, was 66.0, 57.8, and 56.2%, respectively (p < 0.001). Total omega-3 percentages were 2.29% for vegans, 1.55% for vegetarians, and 1.46% for omnivores (p < 0.001). Docosahexaenoic acid percentages were not different by diet pattern, but over 80% of participants had milk concentrations below 0.30% of total fatty acids. Reports of omega-3 supplements use (10/74) and weekly seafood consumption (3/74) were limited. BDNF was not detectable in any samples. CONCLUSIONS: Breast milk from vegans had significantly higher unsaturated fat and total omega-3 fats, and lower saturated fats, trans fats, and omega-6 to omega-3 ratios than their vegetarian and omnivore counterparts. Docosahexaenoic acid concentrations in breast milk were low regardless of maternal diet pattern, and were reflective of low seafood intake and supplement use.

The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution.

Studies into the mechanisms in resolution of self-limited inflammation and acute reperfusion injury have uncovered a new genus of pro-resolving lipid mediators coined specialized pro-resolving mediators (SPM) including lipoxins, resolvins, protectins and maresins that are each temporally produced by resolving-exudates with distinct actions for return to homeostasis. SPM evoke potent anti-inflammatory and novel pro-resolving mechanisms as well as enhance microbial clearance. While born in inflammation-resolution, SPM are conserved structures with functions discovered in microbial defense, pain, organ protection and tissue regeneration, wound healing, cancer, reproduction, and neurobiology-cognition. This review covers these SPM mechanisms and other new omega-3 PUFA pathways that open their path for functions in resolution physiology.

Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria.

Background: Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs). Objective: To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. Methods: We used subsets of fasting plasma and urine samples from our randomized crossover trial in which participants with early-treated classical and variant (milder) PKU consumed a low-Phe diet combined with AA-MFs or GMP-MFs for 3 wk each. Fatty acid profiles of red blood cell (RBC) membranes were determined for 25 adults (aged 18-49 y) with PKU and 143 control participants. Metabolomics analyses of plasma and urine samples were conducted by Metabolon for 9-10 adolescent and adult participants with PKU and for 15 control participants. Results: RBC fatty acid profiles were not significantly different with AA-MFs or GMP-MFs. PKU participants showed higher total n-6:n-3 (ω-6:ω-3) fatty acids (mean ± SD percentages of total fatty acids: AA-MF = 5.45% ± 1.07%; controls = 4.33%; P < 0.001) and lower docosahexaenoic acid (DHA; AA-MF = 3.21% ± 0.98%; controls = 3.70% ± 1.01%; P = 0.02) and eicosapentaenoic acid (AA-MF = 0.33% ± 0.12%; controls = 0.60% ± 0.43%; P < 0.001) in RBCs than did control participants. Despite higher carnitine intake from AA-MFs than GMP-MFs (mean ± SE intake: AA-MFs = 58.6 ± 5.3 mg/d; GMP-MFs = 0.3 ± 0.01 mg/d; P < 0.001), plasma concentrations of carnitine were similar and not different from those in the control group (AA-MF compared with GMP-MF, P = 0.73). AA-MFs resulted in higher urinary excretion of trimethylamine N-oxide (TMAO), which is synthesized by bacteria from carnitine, compared with GMP-MFs (mean ± SE scaled intensity-TMAO: AA-MFs = 1.2 ± 0.1, GMP-MFs = 0.9 ± 0.1; P = 0.005). Plasma deoxycarnitine was lower in PKU participants than in control participants, suggesting reduced carnitine biosynthesis in PKU (AA-MF = 0.9 ± 0.1; GMP-MF = 1.0 ± 0.1; controls = 1.3 ± 0.1; AA-MF compared with controls, P = 0.01; GMP-MF compared with controls, P = 0.04). Conclusions: Supplementation with DHA is needed in PKU. Carnitine supplementation of AA-MFs shows reduced bioavailability due, in part, to bacterial degradation to TMAO, whereas the bioavailability of carnitine is greater with prebiotic GMP-MFs. This trial was registered at www.clinicaltrials.gov as NCT01428258.

Erythrocyte fatty acid composition of Nepal breast-fed infants.

PURPOSE: Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk. METHODS: RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls. RESULTS: In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake. CONCLUSIONS: RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

Effects of fetal genotype and sex on developmental response to maternal malnutrition.

The present study aimed to determine whether developmental patterns, adiposity level and fatty-acid composition of fetuses exposed to maternal malnutrition are driven by their sex or their genotype, or both, as these may modulate the adaptive response to the intrauterine environment independently of the maternal genotype. We used a single maternal genotype (purebred Iberian (IB) sows), which was inseminated with heterospermic semen (obtained by mixing semen from Iberian and Large White (LW) boars), to obtain four different subsets of fetuses (male and female, purebred (IB×IB) and crossbred (IB×LW)) in Iberian purebred sows. Analysis of fetal phenotypes indicated a better adaptive response of the female offspring, which was modulated by their genotype. When faced with prenatal undernutrition, females prioritised the growth of vital organs (brain, liver, lungs, kidneys and intestine) at the expense of bone and muscle. Moreover, the analysis of fat composition showed a higher availability of essential fatty acids in the female sex than in their male counterparts and also in the Iberian genotype than in crossbred fetuses. These results are of high translational value for understanding ethnic differences in prenatal programming of postnatal health and disease status, and show evidence that prenatal development and metabolic traits are primarily determined by fetal sex and strongly modulated by fetal genotype.

Fractionation of the stable carbon isotope ratio of essential fatty acids in zebrafish Danio rerio and mud snails Bellamya chinensis.

Fractionation of stable carbon (C) isotopes in the essential fatty acids 18:2n-6, 18:3n-3, 20:4n-6, 20:5n-3, and 22:6n-3 was investigated in the zebrafish Danio rerio and the mud snail Bellamya chinensis fed the same two diets. These diets differed in essential fatty acid compositions: (1) TetraMin contained all five fatty acids, and (2) Chlorella contained only two, 18:2n-6 and 18:3n-3. On average, the isotopic fractionation was -0.5 ± 0.9 ‰ for 18:2n-6 and 18:3n-3 for all experiments, indicating that the fractionation of these essential fatty acids was negligible. However, the isotopic fractionation of 20:4n-6, 20:5n-3, and 22:6n-3 varied greatly between species and between diets. The isotopic fractionation of the Chlorella diet was -0.2 and -6.9 ‰ for zebrafish and mud snail, but 4.2 and -1.3 ‰, respectively, when these consumers were fed TetraMin. This variation could be explained by the different amount of assimilation and the biosynthesis of these fatty acids from their precursors (i.e., 18:2n-6 and 18:3n-3). These results indicate that the isotopic composition of C20 and C22 essential fatty acids was strongly influenced by the fatty acid composition in the diets. Thus the stable C isotope ratios of C18 essential fatty acids in consumers are more useful as dietary tracers in food web studies.

Dietary LC-PUFA in iron-deficient anaemic pregnant and lactating guinea pigs induce minor defects in the offsprings' auditory brainstem responses.

OBJECTIVES: We previously demonstrated that a mild pre-natal/early post-natal iron-deficient anaemic (IDA) diet devoid of long-chain polyunsaturated fatty acids (LC-PUFA) affected development, neurophysiology, and cerebral lipid biochemistry of the guinea pigs' progeny. Impacts of dietary LC-PUFA on altered cerebral development resulting from pre-natal IDA are unknown. To address this health issue, impacts of mild gestational IDA in the presence of dietary LC-PUFA on the offsprings' neural maturation were studied in guinea pigs using auditory brainstem responses (ABRs) and assessments of brain fatty acids (FAs). METHODS: Female guinea pigs (n = 10/group) were fed an iron sufficient (IS) or IDA diet (146 and 12.7 mg iron/kg, respectively) with physiological amounts of LC-PUFA, during the gestation and lactation periods. From post-natal day (PNd) 9 onwards, the IS + PUFA diet was given to both groups of weaned offspring. Cerebral tissue and offsprings' ABR were collected on PNd24. RESULTS: There was no difference in peripheral and brainstem transmission times (BTTs) between IS + PUFA and IDA + PUFA siblings (n = 10/group); the neural synchrony was also similar in both groups. Despite the absence of differences in auditory thresholds, IDA + PUFA siblings demonstrated a sensorineural hearing loss in the extreme range of frequencies (32, 4, and 2 kHz), as well as modified brain FA profiles compared to the IS + PUFA siblings. DISCUSSION: The present study reveals that siblings born from dams exposed to a moderate IDA diet including balanced physiological LC-PUFA levels during pregnancy and lactation demonstrate minor impairments of ABR compared to the control siblings, particularly on the auditory acuity, but not on neural synchrony, auditory nerve velocity and BTT.

Effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder: a preliminary 1H MRS study.

OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of fish oil (FO) supplementation on cortical metabolite concentrations in adolescents with major depressive disorder (MDD). METHODS: Metabolite concentrations were determined by (1)H MRS in the anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with MDD before and following 10-week open-label supplementation with low (2.4 g/day, n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores and erythrocyte fatty acid levels were also determined. RESULTS: Baseline erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated, and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA) composition was inversely correlated with myo-inositol (mI) concentrations in the left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased, significantly following low-dose and high-dose FO supplementation. In the intent-to-treat sample, depressive symptom severity scores decreased significantly in the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose group (-20%, P = 0.06). There were no significant baseline-endpoint changes in metabolite levels in each voxel. In the low-dose group there were changes with large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18, d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8) and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group, there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d = 1.2). DISCUSSION: These preliminary data suggest that increasing the LCn-3 fatty acid status of adolescent MDD patients is associated with subtle changes in Glx, mI, and Cho concentrations in the DLPFC that warrant further evaluation in a larger controlled trial.

Defining the allometric relationship between size and individual fatty acid turnover in barramundi Lates calcarifer.

An experiment was conducted with barramundi (Asian seabass; Lates calcarifer) to examine the allometric scaling effect of individual fatty acids. Six treatment size classes of fish were deprived of food for 21days (Treatment A, 10.5±0.13g; Treatment B, 19.2±0.11g; Treatment C, 28.3±0.05g; Treatment D, 122.4±0.10g; Treatment E, 217.6±0.36g; Treatment F, 443.7±1.48g; mean±SD) with each treatment comprising of fifteen fish, in triplicate. The assessment of somatic losses of whole-body energy and lipid were consistent with previous studies, validating the methodology to be extended to individual fatty acids. Live-weight (LW) exponent values were determined to be 0.817±0.010 for energy and 0.895±0.007 for lipid. There were significant differences among the fatty acids ranging from 0.687±0.005 for 20:5n-3 (eicosapentaenoic acid) and 0.954±0.008 for 18:1n-9 (oleic acid). The LW exponent values were applied to existing fatty acid intake and deposition data of barramundi fed with either 100% fish oil or 100% poultry oil. From this the maintenance requirement for each fatty acid was determined. The metabolic demands for maintenance and growth were then iteratively determined for fish over a range of size classes. Application of these exponent values to varying levels of fatty acid intake demonstrated that the biggest driver in the utilisation of fatty acids in this species is deposition demand and despite their reputed importance, the long-chain polyunsaturated fatty acids had nominal to no maintenance requirement.

Metabolic programming mediated by an essential fatty acid alters body composition and survival skills of a marine fish.

Metabolic programming occurs when variations in nutrition during a specific developmental window result in long-term metabolic effects. It has been studied almost exclusively in humans and other mammals but never in an ecological context. Here, we report metabolic programming and its functional consequences in a marine fish, red drum. We demonstrate that maternal provisioning of eggs with an essential fatty acid, docosahexaenoic acid (DHA), varies with DHA content of the maternal diet. When offspring are reared on a DHA-replete diet, whole-body DHA content of offspring depends upon the amount of DHA that was in the egg. We further demonstrate that whole-body DHA content is correlated with traits related to offspring fitness (escape responses, routine swimming, growth, and survival). DHA content of red drum eggs produced in nature is in the range where the effects of metabolic programming are most pronounced. Our findings indicate that during a brief developmental window, DHA plays a role in establishing the metabolic capacity for its own uptake or storage, with protracted and possibly permanent effects on ecologically important survival skills of individuals and important implications for dynamics of populations and food webs.

Concise review: Regulation of stem cell proliferation and differentiation by essential fatty acids and their metabolites.

Stem cell therapy holds great promise for regenerative medicine and the treatment of numerous diseases. A key issue of stem cell therapy is the control of stem cell fate, but safe and practical methods are limited. Essential fatty acids, namely ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids (PUFA), and their metabolites are critical components of cell structure and function, and could therefore influence stem cell fate. The available evidence demonstrates that n-6 and n-3 PUFA and their metabolites can act through multiple mechanisms to promote the proliferation and differentiation of various stem cell types. Therefore, elucidating the role of PUFA and their metabolites in stem cell fate regulation is both a challenge and an opportunity for stem cell biology as well as stem cell therapy. PUFA-based interventions to create a favorable environment for stem cell proliferation or differentiation may thus be a promising and practical approach to controlling stem cell fate for clinical applications.