Evidence of the Role of Omega-3 Polyunsaturated Fatty Acids in Brain Glucose Metabolism.

In mammals, brain function, particularly neuronal activity, has high energy needs. When glucose is supplemented by alternative oxidative substrates under different physiological conditions, these fuels do not fully replace the functions fulfilled by glucose. Thus, it is of major importance that the brain is almost continuously supplied with glucose from the circulation.

Very low inadequate dietary intakes of essential n-3 polyunsaturated fatty acids (PUFA) in pregnant and lactating French women: The INCA2 survey.

Background: The French National survey INCA2 pointed out that the majority of the French population (children, adolescents, adults and elderly) ingest low quantities of n-3 polyunsaturated fatty acid (PUFA) in the form of both precursor (alpha-linolenic acid, ALA) and long-chain (mainly docosahexaenoic acid, DHA). However, we don't know whether such inadequate n-3 PUFA consumption is also found again in pregnant and lactating women.

Methods: Dietary lipid and PUFA intakes were determined from 28 pregnant and 21 lactating French women by using the most recent set of national robust data on food (National Survey INCA2 performed in 2006 and 2007), and compared with that of 742 women of childbearing age.

Inadequate daily intakes of n-3 polyunsaturated fatty acids (PUFA) in the general French population of children (3-10 years) and adolescents (11-17 years): the INCA2 survey.

Purpose: This paper deals with the dietary daily intakes of main polyunsaturated fatty acids (PUFA) in French children and adolescents.

Methods: Dietary intakes of main PUFA were determined from a general French population of 1500 children (3-10 years) and adolescents (11-17 years) by using the most recent set of national robust data on food (National Survey INCA 2 performed in 2006 and 2007).

Results: Main results showed that mean daily intakes of total fat and n-6 PUFA linoleic acid (LA, 18:2n-6) were close to current recommended values for children and adolescent populations.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus).

Dietary linoleic acid requirements in the presence of α-linolenic acid are lower than the historical 2 % of energy intake value, study in rats.

Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals.

Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding.

Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats.

Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status.

Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented).

Shallow hypothermia depends on the level of fatty acid unsaturation in adipose and liver tissues in a tropical heterothermic primate.

Optimal levels of unsaturated fatty acids have positive impacts on the use of prolonged bouts of hypothermia in mammalian hibernators, which generally have to face low winter ambient temperatures. Unsaturated fatty acids can maintain the fluidity of fat and membrane phospholipids at low body temperatures. However, less attention has been paid to their role in the regulation of shallow hypothermia, and in tropical species, which may be challenged more by seasonal energetic and/or water shortages than by low temperatures.

Fatty acid composition of the brain, retina, liver and adipose tissue of the grey mouse lemur (Microcebus murinus, primate).

The particular interest in supplementing human foods with n-3 fatty acids has arisen from the findings that this series of polyunsaturated fatty acids (PUFA) have an impact on neuronal functions. Indeed vertebrates, including humans, preferentially use docosahexaenoic acid (DHA, 22:6n-3) over other long-chain n-3 PUFA for the genesis of their neuronal and retinal membranes. The grey mouse lemur is a nocturnal prosimian primate originating from Madagascar.

n-3 PUFA status affects expression of genes involved in neuroenergetics differently in the fronto-parietal cortex compared to the CA1 area of the hippocampus: effect of rest and neuronal activation in the rat.

n-3 Polyunsaturated fatty acids (PUFA) support whole brain energy metabolism but their impact on neuroenergetics in specific brain areas and during neuronal activation is still poorly understood. We tested the effect of feeding rats as control, n-3 PUFA-deficient diet, or docosahexaenoic acid (DHA)-supplemented diet on the expression of key genes in fronto-parietal cortex and hippocampal neuroenergetics before and after neuronal stimulation (activated) by an enriched environment. Compared to control rats, n-3 deficiency specifically repressed GLUT1 gene expression in the fronto-parietal cortex in basal state and also during neuronal activation which specifically stimulated GLUT1.

Oleate metabolism in pig enterocytes is characterized by an increased oxidation rate in the presence of a high esterification rate within two days after birth.

Oleate (OLE) is the principle fatty acid (FA) in mammalian colostrum, but its role in the energy supply in enterocytes after birth remains unknown. We investigated the metabolic fate of OLE in pig enterocytes at birth (d0) and after 2 d of suckling (d2). Cellular TG and phospholipids (PL) and FA composition were analyzed.

Long term adequate n-3 polyunsaturated fatty acid diet protects from depressive-like behavior but not from working memory disruption and brain cytokine expression in aged mice.

Converging epidemiological studies suggest that dietary essential n-3 polyunsaturated fatty acid (PUFA) are likely to be involved in the pathogenesis of mood and cognitive disorders linked to aging. The question arises as to whether the decreased prevalence of these symptoms in the elderly with high n-3 PUFA consumption is also associated with improved central inflammation, i.e.

Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development.

The protection of the developing organism from oxidative damage is ensured by antioxidant defense systems to cope with reactive oxygen species (ROS), which in turn can be influenced by dietary polyunsaturated fatty acids (PUFAs). PUFAs in membrane phospholipids are substrates for ROS-induced peroxidation reactions. We investigated the effects of dietary supplementation with omega-3 PUFAs on lipid peroxidation and antioxidant enzyme activities in rat cerebrum, liver and uterus.

Omega-3 fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate.

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates.

Influence of gender on DHA synthesis: the response of rat liver to low dietary α-linolenic acid evidences higher ω3 ∆4-desaturation index in females.

Purpose: The conversion rate of α-linolenic acid (ALA) into docosahexaenoic acid (DHA) is determined by dietary and non-dietary factors. Higher capacity of DHA synthesis has been evidenced in females, indicating that sex factors influence the conversion pathway. To evaluate the extent to which sexual dimorphism of DHA synthesis is subordinated to nutritional handling, we measured the ω3 ∆4-desaturation index in male and female rats receiving adequate or inadequate amounts of ALA.

Ovariectomy and 17β-estradiol alter transcription of lipid metabolism genes and proportions of neo-formed n-3 and n-6 long-chain polyunsaturated fatty acids differently in brain and liver.

Hormonal and nutritional factors regulate the metabolism of long-chain polyunsaturated fatty acids (LC-PUFA). We aimed to determine whether ovarian hormones influence the capacity of rats to synthesize the end-products 22:6n-3 (DHA) and 22:5n-6 (n-6DPA) from their respective dietary precursors (18:3n-3 and 18:2n-6), and can regulate PUFA conversion enzymes gene transcription in brain and/or liver. Females born with a low DHA status were fed from weaning to 8 weeks of age a diet providing both essential precursors, and were concurrently submitted to sham-operated control (SOC) or ovariectomy (OVX) in combination with or without 17β-estradiol (E2) dosed at 8 or 16 μg/day.

Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations.

The accretion of docosahexaenoic acid (DHA) in membranes of the central nervous system is required for the optimum development of retina and brain functions. DHA status is determined by the dietary intake of n-3 polyunsaturated fatty acids (PUFA), both the metabolic precursor α-linolenic acid (α-LNA) and DHA. Clinical studies have shown that feeding term or premature infants with formula low in total n-3 PUFA may alter the maturation of visual acuity.

Involvement of omega-3 fatty acids in emotional responses and hyperactive symptoms.

Biochemical evidence suggests a role for n-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of behavioral disturbances. A number of studies have revealed an association between reduced n-3 PUFA levels and attention-deficit hyperactivity disorder or depression. Here, we summarize the main findings regarding the association between n-3 PUFA and hyperactive and emotional disorders, and discuss potential mechanisms of action.

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations.

The prevalence of obesity has steadily increased over the last few decades. During this time, populations of industrialized countries have been exposed to diets rich in fat with a high content of linoleic acid and a low content of alpha-linolenic acid compared with recommended intake. To assess the contribution of dietary fatty acids, male and female mice fed a high-fat diet (35% energy as fat, linoleic acid:alpha-linolenic acid ratio of 28) were mated randomly and maintained after breeding on the same diet for successive generations.

n-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells.

Several in vivo studies suggest that docosahexaenoic acid (22:6 n-3), the main n-3 long-chain polyunsaturated fatty acids (LC-PUFA) of brain membranes, could be an important regulator of brain energy metabolism by affecting glucose utilization and the density of the two isoforms of the glucose transporter-1 (GLUT1) (endothelial and astrocytic). This study was conducted to test the hypothesis that 22:6 n-3 in membranes may modulate glucose metabolism in brain endothelial cells. It compared the impact of 22:6 n-3 and the other two main LC-PUFA, arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3), on fatty acid composition of membrane phospholipids, glucose uptake and expression of 55-kDa GLUT1 isoform in two models of rat brain endothelial cells (RBEC), in primary culture and in the immortalized rat brain endothelial cell line RBE4.

Differential effects of steroids on the synthesis of polyunsaturated fatty acids by human neuroblastoma cells.

Polyunsaturated fatty acids (PUFA) are crucial for proper functioning of cell membranes, particularly in brain. Biologically important PUFA include docosahexaenoic acid (n-3 series) and arachidonic acid (n-6 series) which can be formed from their respective dietary essential precursors, alpha-linolenic acid (ALA) and linoleic acid (LA). Steroid hormones are thought to modulate PUFA synthesis in humans but whether they regulate PUFA status in brain and/or in neural membranes is unknown.

Long-chain n-3 fatty acid levels in baseline serum phospholipids do not predict later occurrence of depressive episodes: a nested case-control study within a cohort of middle-aged French men and women.

The goal of this study was to seek the relations between baseline n-3 PUFA status and the later occurrence of depressive episodes in a French cohort of middle-aged men and women, the SU.VI.MAX study.

Gender affects liver desaturase expression in a rat model of n-3 fatty acid repletion.

Dietary n-3 polyunsaturated fatty acids (PUFA) are major components of cell membranes and have beneficial effects on human health. Docosahexaenoic acid (DHA; 22:6n-3) is the most biologically important n-3 PUFA and can be synthesized from its dietary essential precursor, alpha-linolenic acid (ALA; 18:3n-3). Gender differences in the efficiency of DHA bioconversion have been reported, but underlying molecular mechanisms are unknown.

Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice.

Sickness behaviour is an adaptive behavioural response to the activation of the innate immune system. It is mediated by brain cytokine production and action, especially interleukin-6 (IL-6). Polyunsaturated fatty acids (PUFA) are essential fatty acids that are highly incorporated in brain cell membranes and display immunomodulating properties.