Polyunsaturated Fatty Acid Deficiency Research Articles

Early performance, stress- and disease-sensitivity in rainbow trout fry (Oncorhynchus mykiss) after total dietary replacement of fish oil with rapeseed oil. Effects of EPA and DHA supplementation

Different vegetable oils have been investigated as potential substitutes of fish oil in aquaculture feed and several of them have proven to be successful in terms of fish growth rates, survival rates, biometric indices or feeding efficiency, even when used as the only oils in the feed. However, final fish product composition (fish whole body or fish fillet) usually reflects feed composition, and fish products from fish fed with only vegetable oils usually show a deficiency in long chain polyunsaturated fatty acids (PUFAs). The welfare and health consequences for the fish of these alterations of the fatty acid profile are not well known. In the current study, three experimental diets using supercritically defatted fish meal as well as rapeseed oil as a 100% replacement of fish oil, and differing in essential fatty acid (eicosapentaneoid acid - EPA, docosahexaenoic acid - DHA) supplementation, were tested in rainbow trout, Oncorhynchus mykiss. The growth performance, feed conversion ratio and digestive enzyme profiles were evaluated. Further, stress-and infection-challenge experiments were performed to assess the robustness of the fish against stress and disease. The trout fry fed the experimental diets showed a different fatty acid profile than fish fed a commercial diet, with lower EPA and DHA levels but higher linolenic acid (18:3n-3) and oleic acid (18:1n-9) levels. No significant effects were found in growth performance, feed conversion ratio or digestive enzymatic activity among diets. The fish stress responsiveness (brain and plasma stress marker response) to acute and repeated stressors was in general also similar irrespective of the diet. Infection trials, however, showed a differential ability of the fish to survive upon a controlled infection with the bacterium Flavobacterium psychrophilum. Fish fed with the experimental diets displayed higher mortalities than fish fed a commercial trout fry diet. The current results highlight the need of further research on nutritional requirements to optimize the disease resilience in farmed fish. These results also demonstrate that the adaptation of the fish to new formulated feed (in this case associated to plant oil ingredients) should not be assessed solely based on the growth performance of the fish. Other aquaculture relevant welfare indicators, as disease or stress resilience, should be part of a more complete assessment of feed adequacy for fish farming purposes.

Food security and the nutritional status of children in foster care: new horizons in the protection of a fragile population.

The nutritional status of foster children, the quality of daily menus in group homes and the Food Security inside these organizations have been poorly studied and this study means to investigate them. A sample of 125 children, ranging in age from 0-17 years, among seven group homes (group A) was compared with 121 children of the general population we (group B). To evaluate nutritional status, BMI percentiles were used. Mean percentiles of both groups were compared through statistical analysis. Both nutritional and caloric daily distributions in each organization were obtained using the 24-hour recall method. A specific questionnaire was administered to evaluate Food Security. From the analysis of mean BMI-for-age (or height-for-length) percentiles, did not observe statistically significant differences between group A and group B. The average daily nutrient and calorie distribution in group homes proves to be nearly optimal with the exception of a slight excess in proteins and a slight deficiency in PUFAs. Moreover, a low intake of iron and calcium was revealed. All organizations obtained a "High Food Security" profile. Nutritional conditions of foster children are no worse than that of children of the general population. Foster care provides the necessary conditions to support their growth.

The effect of polyunsaturated fatty acid deficiency on allergic response in ovalbumin-immunized mice

Polyunsaturated fatty acids (PUFAs) are present in biological membranes and influence membrane fluidity and immune responses. PUFAs such as 18:2n–6 and 18:3n–3 cannot be synthesized de novo in mammals and are thus called essential fatty acids (EFAs). In addition, PUFAs can be converted to very long-chain PUFAs (VLC-PUFAs), such as arachidonic acid and docosahexaenoic acid, in the body. Although avoiding allergens is an effective strategy for food-allergy patients, the dietary exclusion of several allergens reportedly induces deficiencies in essential nutrients such as PUFAs. In this study, we investigated whether an EFA-deficient (EFAD) diet influenced allergic symptoms in ovalbumin (OVA)-immunized mice. Unexpectedly, no exacerbation of immune responses after OVA-sensitization was observed in mice fed an EFAD diet, and no differences in serum PUFA levels between OVA-immunized and non-immunized mice fed the EFAD diet were detected. However, levels of VLC-PUFAs in the small intestine increased after OVA-sensitization and did not decrease during EFAD diet administration, showing that small intestinal VLC-PUFAs levels were strongly preserved in the food-allergy model mice. Further studies are required to elucidate the mechanisms by which small intestinal VLC-PUFAs are retained in food-allergy model mice.

Polyunsaturated fatty acid deficiency and pediatric neuropsychiatric morbidity

Child morbidity and disability is a national problem in any country, and measures to reduce it are the priority for every society. Recent years, children’s diseases such as neuropsychiatric diseases, (24,3%), nervous system diseases (22.9%); congenital anomalies (malformations), deformations and chromosomal disorders (16.2%). The absolute value of disabled children with nervous system diseases as of January 1, 2020 was 157,727. At all stages of the nervous system formation, the process of cell membranes formation, covering both glial cells and neurons themselves (and their branches - dendrites and axons), progresses actively. Cell membranes consist mainly of phospholipids, which are synthesized from long chain polyunsaturated fatty acids coming from food. In an attempt to determine the reasons for the growing disability of the child population, the researchers drew attention to the changed nature of the nutrition of society in general and the child population in particular over the past century. One of the significant components of the diet that affects the formation and development of the nervous system and the mental sphere were polyunsaturated fatty acids, some of which, with an unbalanced diet, can’t be obtained by the body from sources alternative to food. In this review, we observe the experience of correcting the nutritional status of young children and pregnant and lactating women with omega-3 polyunsaturated fatty acids. Numerous studies have confirmed the fact that there is a relationship between omega-3 polyunsaturated fatty acids deficiency, neurological deficiency and reduced intellectual abilities of a child.

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

Effects Of 8-Weeks Of Blueback-fish Consumption On Gut Microbiota In Elite Japanese Nordic Combined Athletes

PURPOSE: It is important for athletes in winter sports to maintain good conditions for performance during overseas expedition. Recently, differences in gut microbiota among athletes have been reported related to inflammation and performance. Omega-3 polyunsaturated fatty acid (PUFA) potential action in restoring eubiosis in gut microbiota (Costantini et al. 2017). On the other hands, n-3 PUFA deficiency induces a state of gut dysbiosis through alteration of gut microbiota composition(Robertson et al. 2017). However, in the athletes, the chronic effect of n-3 PUFA (blueback-fish)-riched foods intake on the gut microbiota is remains unclear. The present study investigated whether 8-weeks dietary n-3 PUFA enhances gut microbiota in athletes. METHODS: Six male (27 ± 6 yrs) elite Japanese Nordic combined athletes consumed processed foods containing blue-backed fish [800 mg eicosapentaenoic acid (EPA), 1300 mg docosahexiaenoic acid/time] 4-5 times a week and continued for 8-weeks. Before and after the intervention, blood variables and gut microbiota, dietary surveys were evaluated. The gut microbiota was measured by Illumina sequencing of the bacterial 16S rRNA gene. RESULTS: As a result of the dietary survey, there was no significant change in the energy intake and the intake of fish before and after the intervention except food of intervention. Resting concentrations of serum EPA (49 ± 18μg/mL vs.108 ± 38 μg/mL, p = 0.01) and EPA/AA ratio (0.26 ± 0.1 vs. 0.68 ± 0.3, p = 0.01) were significantly elevated in after intervention. In gut microbiota, in after intervention decreased the indicator related to obesity and inflammation Firmicutes/Bacteroidetes ratio and significantly increased proportion of Bifidobacteria which lipopolysaccharide-suppressing bacteria (2.4 ± 2.1% vs. 6.7 ± 5.4 %, p = 0.046). CONCLUSIONS: A 8-weeks consumption of processed foods containing blueback-fish increased blood n-3 PUFA concentration and the presence of health-related taxa in gut microbiota. It may be possible the positive impact on gut microbiota in Japanese Nordic combined athletes.

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy-mediated degradation.

Metabolic changes in sulfatides and other sulfated glycans have been related to various diseases, including Alzheimer's disease (AD). However, the importance of polyunsaturated fatty acids (PUFA) in sulfated lysosomal substrate metabolism and its related disorders is currently unknown. We investigated the effects of deficiency or supplementation of PUFA on the metabolism of sulfatides and sulfated glycosaminoglycans (sGAGs) in sulfatide-rich organs (brain and kidney) of mice. A PUFA-deficient diet for over 5weeks significantly reduced the sulfatide expression by increasing the sulfatide degradative enzymes arylsulfatase A and galactosylceramidase in brain and kidney. This sulfatide degradation was clearly associated with the activation of autophagy and lysosomal hyperfunction, the former of which was induced by suppression of the Erk/mTOR pathway. A PUFA-deficient diet also activated the degradation of sGAGs in the brain and kidney and that of amyloid precursor proteins in the brain, indicating an involvement in general lysosomal function and the early developmental process of AD. PUFA supplementation prevented all of the above abnormalities. Taken together, a PUFA deficiency might lead to sulfatide and sGAG degradation associated with autophagy activation and general lysosomal hyperfunction and play a role in many types of disease development, suggesting a possible benefit of prophylactic PUFA supplementation.

Maternal dietary deficiency of n-3 fatty acids affects metabolic and epigenetic phenotypes of the developing fetus

Polyunsaturated fatty acids (PUFAs) play multiple physiological roles. They regulate the structure and function of cell membranes and cell growth and proliferation, and apoptosis. In addition, PUFAs are involved in cellular signaling, gene expression and serve as precursors to second messengers such as eicosanoids, docosanoids etc. and regulate several physiological processes including placentation, inflammation, immunity, angiogenesis, platelet function, synaptic plasticity, neurogenesis, bone formation, energy homeostasis, pain sensitivity, stress, and cognitive functions. Linoleic acid, 18:2n-6 (LA) and alpha-linolenic acid, 18:3n-3 (ALA) are the two essential fatty acids obtained from the diets and subsequently their long-chain polyunsaturated fatty acids (LCPUFAs) are accumulated in the body. The maternal plasma LCPUFAs especially accumulated in larger amounts in the brain during the third trimester of pregnancy via the placenta and postnatally from mother's breast milk. Various studies, including ours, suggest PUFA's important role in placentation, as well as in growth and development of the offspring. However, intakes of maternal n-3 PUFAs during pregnancy and lactation are much lower in India compared with the Western population. In India, n-3 fatty acid status is further reduced by higher intake of n-6 PUFA rich oils and trans fats. More data on the impacts of long term maternal n-3 PUFA deficiency on placental structure and function, gene expression, epigenetic changes and resultant cognitive function of fetus & infants are emerging. This review summarizes the impacts of n-3 PUFA deficiency in utero on fetal growth and development, adiposity, energy metabolism, musculoskeletal development, and epigenetic changes in feto-placental axis from the recently available pre-clinical and clinical data.

MON-129 Analysis of Omega3 PUFAs Status Among the Female and Male Population of the Moscow Region

INTRODUCTION:All humans have levels of EPA+DHA that if methodologically correctly assessed in erythrocytes, are optimal more than 8%. Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest not only in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias, but also many serious health issues that can be prevented by optimal levels. OBJECTIVE: The aim of this study was to assess in a retrospective study the omega-3 PUFAs status at Moscow region according age and sex.SUBJECTS AND METHODS:In this retrospective study, the records of 1349 patients who presented with various complaints in the period from 2013 to 2017 aged 1 to 91 were examined. Fatty acids within the red blood cell membranes were analyzed as methyl ethers after trans-esterification with sodium methylate using GC-MS followed by omega-3 index calculation.RESULTS:Deficiency of omega-3 PUFAs was found in 68.5% of patients. The most severe deficiency was noted in children and adolescents aged 0 to 17 years (in girls to a greater extent). In age groups of 18–44 and 45–59 years, the prevalence of severe (<4%) and moderate (4–8%) deficiency was comparable in males and females: among 18–44-year-old men severe deficiency was noted in 5.6%, moderate – in 29.4%, at the age of 45–59 years – in 7 and 23%, respectively; among women – 6.4, 24.4, 8.4 and 20%, respectively. In the age group of 60-74 years, prevalence of severe deficiency was significantly higher in men, who had severe deficiency in 9.2% of cases, whereas in women of the same age it was found only in 4.8% of cases, the prevalence of moderate deficiency is 23 and 23.8%, respectively.CONCLUSIONS:Such high prevalence of severe omega-3 PUFA deficiency in girls under 17 is likely due to girls’ and their parents’ concerns about weight, diet and veganism, and requires the inclusion of omega-3 index analysis in adolescent girls’ screening. Thus, during the most important period – the period of puberty – 25% of girls have metabolic and hypoxic disorders due to deficiency of omega-3 PUFA and are at risk of not only diseases associated with metabolic disorders, but also reproductive disorders (infertility, miscarriage, fetal malformations). The obtained data is indicative of the necessity to choose dosages of omega-3 PUFAs, considering not only the patients age, but also their gender.

Differential Metabolomic Analysis of Liver Tissues from Rat Models of Parenteral Nutrition-Associated Liver Disease.

Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure, but parenteral nutrition-associated liver disease (PNALD) limits its long-term use. The present study is aimed at determining which pathways are altered most notably in a rat model of PNALD. We randomly assigned male Sprague-Dawley (SD) rats into two different groups, whereby they received either enteral nutrition (EN) or PN. Liver tissues were harvested from all rats 7 days later for metabolomic profiling. The composition of primary conjugated bile acids was altered, the synthesis of polyunsaturated fatty acids was reduced, the conversion of pyruvate to acetyl-CoA was blocked, and the synthesis of phosphatidylcholine was inhibited in rats with PNALD. Riboflavin, which is involved in the electron transfer process in the mitochondrial electron transport chain, was remarkably decreased in PNALD rats. A deficiency of polyunsaturated fatty acids, riboflavin, choline, and taurine might be involved in the progression of PNALD. The implications of these findings for the field of medicine are that supplementation with polyunsaturated fatty acids, riboflavin, choline, and taurine might have potential as therapeutic strategies for PNALD and also shed light on the mechanisms of PNALD.

Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits

Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 polyunsaturated fatty acid (PUFA) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2-expressing neurons normalizes MSN collateral inhibition and enhances motivation. These results constitute the first demonstration of a causal link between a behavioral deficit and n-3 PUFA decrease in a discrete neuronal population and suggest that lower n-3 PUFA biostatus in psychopathologies could participate in the etiology of reward-related symptoms.

Reevaluating Polyunsaturated Fatty Acid Essentiality in Nile Tilapia

AbstractNile Tilapia Oreochromis niloticus have a reported dietary requirement for the n‐6 C18 polyunsaturated fatty acid (PUFA) 18:2n‐6 (linoleic acid), but direct provision of the n‐6 long‐chain (LC) PUFA 20:4n‐6 (arachidonic acid) may be a more efficient approach. No quantitative requirement for n‐3 fatty acids has been formally recognized for tilapias, but beneficial effects of having both n‐3 and n‐6 PUFAs in the diet have been reported. To better understand PUFA essentiality in tilapias, we formulated diets to assess the growth performance and tissue fatty acid composition of juvenile Nile Tilapia (mean ± SD = 25.7 ± 0.2 g/fish) that were fed different combinations of n‐3 and n‐6 PUFAs: a positive control containing menhaden fish oil, a negative control containing hydrogenated soybean oil, and experimental diets containing hydrogenated soybean oil amended with ethyl esters of 18:3n‐3; 18:3n‐3 and 18:2n‐6; 22:6n‐3; 22:6n‐3 and 20:4n‐6; or 20:5n‐3, 22:6n‐3, and 20:4n‐6. After 7 weeks, weight gain, feed conversion ratio, and specific growth rate were significantly greater among fish that received the positive control feed than among fish that were fed the negative control feed. The addition of n‐3 and n‐6 PUFA supplements generally improved performance in most cases. No fish showed any gross indications of fatty acid deficiency, although significant differences in fatty acid deficiency indicator ratios (i.e., 20:3n‐9 : 20:4n‐6 and 22:5n‐6 : 22:6n‐3) were present in all tissues analyzed. Nile Tilapia that were fed an n‐3 PUFA‐free diet exhibited significantly elevated 22:5n‐6 : 22:6n‐3 ratios, indicating a developing n‐3 PUFA deficiency. Feeding n‐3 PUFAs—as 18:3n‐3, 22:6n‐3, or a combination of n‐3 LC‐PUFAs—had a corrective effect on these ratios, affirming the importance of a proper balance of n‐3 and n‐6 PUFAs to satisfy the essential fatty acid requirements of Nile Tilapia and further illustrating the ability of this species to satisfy physiological demand for LC‐PUFAs through de novo biotransformation of C18 PUFAs.

Maternal n-3 PUFAs deficiency during pregnancy inhibits neural progenitor cell proliferation in fetal rat cerebral cortex

The aim of this study was to evaluate the in vivo impacts of maternal n-3 polyunsaturated fatty acids (PUFAs) deficiency during pregnancy on the proliferation of neural progenitor cells (NPCs) in the developing cerebral cortex of fetal rats. Our results showed that about 5 weeks of maternal dietary n-3 PUFAs deprivation resulted in a substantial n-3 PUFA deficiency in fetal rat cerebral cortex. Importantly, by two survival schemes and two quantitative methods, we found that maternal intake of n-3 PUFAs deficient diet during the gestation significantly inhibited the proliferation of NPCs in fetal rat cerebral cortex. Moreover, the decreased cortical NPCs proliferation induced by nutritional n-3 PUFAs restriction did not originate from the increased NPCs apoptosis. Finally, our observations indicated that the down-regulation of cyclin E protein might be involved in the inhibitory effects of maternal n-3 PUFAs deficient diet on the proliferation of cortical NPCs. These findings highlight the importance of maternal intake of appropriate n-3 PUFAs and deepen our understanding of the exact effects of n-3 PUFAs on mammalian brain development.

Leukoencephalomyelopathy in cats linked to abnormal fatty acid composition of the white matter of the spinal cord and of irradiated dry cat food.

Four outbreaks of leukoencephalomyelopathy in colonies of SPF cats on a long‐term diet of irradiated dry cat food were observed in the Netherlands between 1989 and 2001. As a primary defect in myelin formation was suspected to be the cause of the disease and myelin consists mainly of lipids and their fatty acids, we investigated the fatty acid composition of the white matter of the spinal cord of affected and control cats and of irradiated and non‐irradiated food. The irradiated food had low levels of alpha‐linolenic acid compared to linoleic acid as well as a high total omega‐6:omega‐3 ratio of 7:1 in the irradiated and of 2:1 in the non‐irradiated food. The white matter of the spinal cord showed low levels of linoleic acid and absence of alpha‐linolenic acid in affected cats as well as absence of lignoceric and nervonic acid in both affected and control cats. These abnormalities in fatty acid composition of the white matter of the spinal cord may reflect an increased need for alpha‐linolenic acid as a substrate for longer chain omega‐3 fatty acids to compose myelin and thus indicate a particular species sensitivity to dietary deficiency in omega‐3 polyunsaturated fatty acids, particularly alpha‐linolenic acid in cats. Our findings indicate that abnormalities in fatty acid metabolism in myelin play an essential role in the pathogenesis of this acquired form of leukoencephalomyelopathy in cats.

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial.

BackgroundDeficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis.MethodsA total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. ResultsThe n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms.ConclusionsPartially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group.Clinical Trial RegistrationANZCTR, identifier: 12608000475347

Dietary N-3 PUFA deficiency affects sleep-wake activity in basal condition and in response to an inflammatory challenge in mice

Essential polyunsaturated fatty acids (PUFA) from the n-3 and n-6 series constitute the building blocks of brain cell membranes where they regulate most aspects of cell physiology. They are either biosynthesized from their dietary precursors or can be directly sourced from the diet. An overall increase in the dietary n-6/n-3 PUFA ratio, as observed in the Western diet, leads to reduced n-3 PUFAs in tissues that include the brain. Some clinical studies have shown a positive correlation between dietary n-3 PUFA intake and sleep quantity, yet evidence is still sparse. We here used a preclinical model of dietary n-3 PUFA deficiency to assess the precise relationship between dietary PUFA intake and sleep/wake activity. Using electroencephalography (EEG)/electromyography (EMG) recordings on n-3 PUFA deficient or sufficient mice, we showed that dietary PUFA deficiency affects the architecture of sleep-wake activity and the oscillatory activity of cortical neurons during sleep. In a second part of the study, and since PUFAs are a potent modulator of inflammation, we assessed the effect of dietary n-3 PUFA deficiency on the sleep response to an inflammatory stimulus known to modulate sleep/wake activity. We injected mice with the endotoxin lipopolysaccharide (LPS) and quantified the sleep response across the following 12 h. Our results revealed that n-3 PUFA deficiency affects the sleep response in basal condition and after a peripheral immune challenge. More studies are now required aimed at deciphering the molecular mechanisms underlying the intimate relationship between n-3 PUFAs and sleep/wake activity.

Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits

Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 Polyunsaturated Fatty Acids (PUFAs) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational deficits. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor (D2R)-expressing medium spiny neurons (iMSNs) onto dopamine D1 receptor-expressing (d)MSNs in the nucleus accumbens, a main brain region for the modulation of motivation. Strikingly, transgenically preventing n-3 PUFA deficiency selectively in D2R-expressing neurons normalizes MSNs collateral inhibition and enhances motivation. These results constitute the first demonstration of a causal link between a behavioral deficit and n-3 PUFA decrease in a discrete neuronal population and suggest that lower n-3 PUFA biostatus in psychopathologies could participate to the etiology of reward-related symptoms.

Omega-3 Polyunsaturated Fatty Acid Deficiency and Progressive Neuropathology in Psychiatric Disorders: A Review of Translational Evidence and Candidate Mechanisms.

Meta-analytic evidence indicates that mood and psychotic disorders are associated with both omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficits and progressive regional gray and white matter pathology. Although the association between omega-3 PUFA insufficiency and progressive neuropathological processes remains speculative, evidence from translational research suggests that omega-3 PUFA insufficiency may represent a plausible and modifiable risk factor not only for enduring neurodevelopmental abnormalities in brain structure and function, but also for increased vulnerability to neurodegenerative processes. Recent evidence from human neuroimaging studies suggests that lower omega-3 PUFA intake/status is associated with accelerated gray matter atrophy in healthy middle-aged and elderly adults, particularly in brain regions consistently implicated in mood and psychotic disorders, including the amygdala, anterior cingulate, hippocampus, prefrontal cortex, and temporal cortex. Human neuroimaging evidence also suggests that both low omega-3 PUFA intake/status and psychiatric disorders are associated with reductions in white matter microstructural integrity and increased rates of white matter hyperintensities. Preliminary evidence suggests that increasing omega-3 PUFA status is protective against gray matter atrophy and deficits in white matter microstructural integrity in patients with mood and psychotic disorders. Plausible mechanisms mediating this relationship include elevated pro-inflammatory signaling, increased synaptic regression, and reductions in cerebral perfusion. Together these associations encourage additional neuroimaging research to directly investigate whether increasing omega-3 PUFA status can mitigate neuropathological processes in patients with, or at high risk for, psychiatric disorders.

Dietary Omega-3 Polyunsaturated Fatty Acid Deprivation Does Not Alter Seizure Thresholds but May Prevent the Anti-seizure Effects of Injected Docosahexaenoic Acid in Rats.

Background: Brain concentrations of omega-3 docosahexaenoic acid (DHA, 22:6n-3) have been reported to positively correlate with seizure thresholds in rodent seizure models. It is not known whether brain DHA depletion, achieved by chronic dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency, lowers seizure thresholds in rats.Objective: The present study tested the hypothesis that lowering brain DHA concentration with chronic dietary n-3 PUFA deprivation in rats will reduce seizure thresholds, and that compared to injected oleic acid (OA), injected DHA will raise seizure thresholds in rats maintained on n-3 PUFA adequate and deficient diets.Methods: Rats (60 days old) were surgically implanted with electrodes in the amygdala, and subsequently randomized to the AIN-93G diet containing adequate levels of n-3 PUFA derived from soybean oil or an n-3 PUFA-deficient diet derived from coconut and safflower oil. The rats were maintained on the diets for 37 weeks. Afterdischarge seizure thresholds (ADTs) were measured every 4–6 weeks by electrically stimulating the amygdala. Between weeks 35 and 37, ADTs were assessed within 1 h of subcutaneous OA or DHA injection (600 mg/kg). Seizure thresholds were also measured in a parallel group of non-implanted rats subjected to the maximal pentylenetetrazol (PTZ, 110 mg/kg) seizure test. PUFA composition was measured in the pyriform-amygdala complex of another group of non-implanted rats sacrificed at 16 and 32 weeks.Results: Dietary n-3 PUFA deprivation did not significantly alter amygdaloid seizure thresholds or latency to PTZ-induced seizures. Acute injection of OA did not alter amygdaloid ADTs of rats on the n-3 PUFA adequate or deficient diets, whereas acute injection of DHA significantly increased amygdaloid ADTs in rats on the n-3 PUFA adequate control diet as compared to rats on the n-3 PUFA deficient diet (P < 0.05). Pyriform-amygdala DHA percent composition did not significantly differ between the groups, while n-6 docosapentaenoic acid, a marker of n-3 PUFA deficiency, was significantly increased by 2.9-fold at 32 weeks.Conclusion: Chronic dietary n-3 PUFA deficiency does not alter seizure thresholds in rats, but may prevent the anti-seizure effects of DHA.

Editorial introductions

Editorial introductions