Essential fatty acids and their role in the treatment of impulsivity disorders

Essential fatty acids (EFAs) have been shown to benefit patients with depression, schizophrenia and dementia. More recently, their role in disorders characterised by impulsivity has attracted some attention. The psychiatric conditions of attention-deficit hyperactivity disorder and borderline personality disorder as well as the phenomena of deliberate self-harm and violence have been ameliorated by the supplementation of EFAs in a number of recent clinical trials. This paper summarises the burgeoning clinical and basic research indicating the existence of significant deficits of EFAs in impulsivity disorders and the supplementation studies of EFAs in these diverse conditions, all of which remain a major therapeutic challenge.     

Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease

Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alapha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E₁, (PGE₁), prostacyclin (PGI₂), and PGI₃, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians. Since insulin resistance and hyperinsulinemia and features of obesity, NIDDM, HTN and CHD, diseases that are common in Indians, and as decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids (PUFAs) in skeletal muscle phospholipids and, possibly, in the plasma, the possibility is raised that changes in the metabolism of EFAs may have a fundamental role in the pathobiology of these conditions. If this is true, this suggests that supplementation of GLA, DGLA, AA, EPA and/or DHA may be indicated to prevent CHD, HTN and NIDDM in Indians.     

The beneficial effects of omega-3 and omega-6 essential fatty acid supplementation on red blood cell rheology.

Twenty healthy, non-smoking subjects were enrolled into a study to investigate the effects of dietary supplementation with essential fatty acid (EFAs) on red blood cell rheology. Ten subjects were given 3 months dietary supplementation with long chain polyunsaturated EFAs containing omega-3 and omega-6 EFAs while 10 others were given placebo (sunflower oil). Venous sampling was performed at 0 and 12 weeks and red blood cell (RBC) aggregation and deformability measured by a filtration system. The results showed a reduction in RBC aggregation in the group given omega-3 and omega-6 EFAs but not in the placebo group. This may be related to changes in the RBC membrane and surface receptor characteristics. Such EFAs may be useful in Raynaud's phenomenon.     

Microbial production of omega-3 fatty acids: an overview

The essence of appropriate nutritional intake on a regular basis has a great impact in maintaining fundamental physiological functions and the body metabolism. Considering how pivotal maintaining a nourishing fat diet is to human health, Omega-3 fatty acids have gained a lot of attention in recent times. Omega-3 fatty acids (n-3 FAs) such as eicosapentaenoic acid (EPA) and DHA are considered as essential fatty acids (EFAs) offering enormous nutritional benefits: from playing a major role in the prevention and treatment of a number of human diseases, such as cardiovascular disorders and neurological disorders, to having anti-inflammatory properties, to providing joint support, etc. Hence, their incorporation into our daily diet is of great importance. Also, both EPA and DHA have been shown to be therapeutically significant in treating several infectious diseases. EFAs were initially thought to be marine in origin, produced by fishes. Consequentially, this led to the increase in the industrial extraction of fish oils for meeting the commercial need for of n-3-rich dietary supplements. Although fish oil supplementation met almost all of the dietary demand for EFAs, they did come with a fair share of drawbacks such as undesirable odour and flavour, heavy metal contamination, extinction of fish species, etc. Oleaginous micro-organisms are a promising alternative for the production of a more sustainable, consistent and quality production of n-3 FAs. Thus, the entire review focuses on understanding the eco-friendlier production of n-3 FAs by micro-organisms.     

Keloids in rural black South Africans. Part 2: dietary fatty acid intake and total phospholipid fatty acid profile in the blood of keloid patients

In the second part of this study, emphasis is placed on nutritional intakes (fatty acids and micronutrients) and fatty acid intake and metabolism in the blood, respectively, according to a combined 24 h recall and standardized food frequency questionnaire analyses of keloid prone patients (n=10), compared with normal black South Africans (n=80), and total phospholipid blood (plasma and red blood cell ) analyses of keloid patients (n=20), compared with normal individuals (n=20). Lipid extraction and fractionation by standard procedures, total phospholipid (TPL) separation with thin layer chromatography, and fatty acid methyl ester analyses with gas liquid chromatography techniques were used. Since nutrition may play a role in several disease disorders, the purpose of this study was to confirm or refute a role for essential fatty acids (EFAs) in the hypothesis of keloid formations stated in part 1 of this study. (1)According to the Canadian recommendation (1991), we observed that in keloid patients linoleic acid (LA) and arachidonic acid (AA) dietary intakes, as EFAs of the omega-6-series, are higher than the recommended 7-11 g/d. However, the a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary intakes, as EFAs of the omega-3 series, are lower than the recommendation of 1.1-1.5 g/d. This was also the case in the control group, where a higher dietary intake of the omega-6 fatty acids and a slightly lower dietary intake of the omega-3 fatty acids occurred. Thus, we confirm a high dietary intake of LA (as a product of organ meats, diary products and many vegetable oils) and AA (as a product of meats and egg yolks), as well as lower dietary intakes of ALA (as a product of grains, green leafy vegetables, soy oil, rapeseed oil and linseed), and EPA and DHA (as products of marine oils). Lower micronutrient intakes than the recommended dietary allowances were observed in the keloid group that may influence EFA metabolism and/or collagen synthesis. Of cardinal importance may be the lower intake of calcium in the keloid patients that may contribute to abnormal cell signal transduction in fibroblasts and consequent collagen overproduction, and the lower copper intake that may influence the immune system, or perhaps even the high magnesium intake that stimulates metabolic activity. Micronutrient deficiencies also occurred in the diets of the normal black South Africans that served as a control group. In the case of plasma TPLs, deficiency of the omega-3 EFA series (ALA, EPA and DHA) occurred, and this is in accordance with the apparent lower omega-3 EFA intake in the diets of these patients. In the case of the red blood cell TPLs, as a true and reliable source of dietary fatty acid intake and metabolism, sufficient EFAs of the omega-6 series (LA and AA) and the omega-3 series (ALA, EPA and DHA) occurred. For this study group a relative deficiency of nutritional omega-3 EFA intake apparently did occur, but was probably compensated for by blood fatty acid metabolism.     

New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism.

Phospholipids make up about 60% of the brain's dry weight. In spite of this, phospholipid metabolism has received relatively little attention from those seeking genetic factors involved in psychiatric and neurological disorders. However, there is now increasing evidence from many quarters that abnormal phospholipid and related fatty acid metabolism may contribute to illnesses such as schizophrenia, bipolar disorder, depression and attention deficit hyperactivity disorder. To date the possible specific proteins and genes involved have been relatively ill-defined. This paper reviews the main pathways of phospholipid metabolism, emphasizing the roles of phospholipases of the A2 and C series in signal transduction processes. It identifies some likely protein candidates for involvement in psychiatric and neurological disorders. It also reviews the chromosomal locations of regions likely to be involved in these disorders, and relates these to the known locations of genes directly or indirectly involved in phospholipid and fatty acid metabolism.     

Modulation of intestinal vitamin D receptor availability and calcium ATPase activity by essential fatty acids

The physiological mechanisms by which essential fatty acids (EFAs) affect calcium (Ca(2+)) retention is not clear, but suggestions have included changes in membrane fluidity, receptor modulation and induction of second messengers. The vitamin D receptor (VDR) is essential for the functioning of 1,25(OH)(2)D(3)which increases Ca(2+)absorption. Activity of the intestinal basolateral membrane (BLM) Ca(2+)ATPase correlates with the degree of Ca(2+)absorption. Therefore, changes in ATPase activity and VDR availability due to EFAs may influence calcium retention. We have investigated the effect of long-term dietary supplementation with EFAs on Ca(2+)ATPase activity (measured colourimetrically) and VDR availability (measured with the ELISA technique) after the loss of oestrogen induced by ovariectomy (OVX) in female Sprague Dawley rats. Control animals underwent anaesthesia and a surgical procedure but the ovaries were left intact (sham). Ca(2+)ATPase activity was significantly lower in OVX animals than in the intact animals (P<0.05) and following supplementation with EFAs, was significantly higher than in sham controls (P<0.05). A higher number of VDR was measured after OVX and declined due to EFA supplementation; these differences in activity of the ATPase and number of receptors could be ascribed to membrane changes due to EFA supplementation, feedback control by serum calcium or the direct influence of the EFAs.     

GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus.

It is now believed that the GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes have an important role in the development of obesity and non-insulin dependent diabetes mellitus (NIDDM). The protein encoded by daf-2 is 35% identical to the human insulin receptor, daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 can enhance superoxide dismutase (SOD) expression. EFAs and their metabolites can alter the cell membrane fluidity and enhance the expression of GLUT-4 and insulin receptors. EFAs can suppress TNF-alpha production and secretion, a mechanism that may have relevance to the role of these fatty acids in the pathogenesis of insulin resistance, obesity and NIDDM. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Based on this evidence, it is proposed that GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin interact with each other in ways which may have relevance to the development or abrogation of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.     

Potential diagnostic aids for abnormal fatty acid metabolism in a range of neurodevelopmental disorders

Disorders of neurodevelopment include attention deficit hyperactivity disorder, dyspraxia, dyslexia and autism. There is considerable co-morbidity of these disorders and their identification often presents difficulties to those making a diagnosis. This is especially difficult when a multidisciplinary approach is not adopted. All of these disorders have been reported as associated with fatty acid abnormalities ranging from genetic abnormalities in the enzymes involved in phospholipid metabolism to symptoms reportedly improved following dietary supplementation with long chain fatty acids. If definitive disorders of lipid metabolism could be defined then the diagnosis and subsequent management of neurodevelopmental disorders might be transformed. In the identification of those disorders of development which involve lipid metabolism, there are now several tests, measures of lipid metabolism, which could be useful.     

Exchange of unsaturated fatty acids between adipose tissue and atherosclerotic plaque studied with artificial neural networks

The linoleic C18:2 (n-6) and linolenic C18:3 (n-3) are recognized as essential components of the diet. Free radical peroxidation of essential fatty acids (EFAs) present in lipoproteins produces oxidized low-density lipoproteins which play a critical role in the development of atherosclerosis. The accumulation of EFAs in the vascular wall and correlations between their content in the adipose tissue and atherosclerotic plaque have been confirmed. The present study was undertaken to determine the usefulness of a neural network for studying the exchange between tissues of linoleic, alpha-linolenic, and arachidonic acids-three fatty acids with a well-understood metabolism. Atheromatous plaques, adipose tissue, and serum were obtained from 31 patients who underwent surgery due to atherosclerotic stenosis of the abdominal aorta, iliac or femoral arteries. Fatty acids were extracted and separated as methyl esters using gas chromatography. Statistical analysis was done with STATISTICA neural networks package. Several correlations reported previously were corroborated and factors modifying the content of individual EFAs in adipose tissue and atherosclerotic plaque were revealed. Artificial neural networks (ANNs) were used to determine factors modifying the content of linoleic, alpha-linolenic, and arachidonic acids in human atheromatous plaques. The mechanism of exchange of some fatty acids between the adipose tissue, atheromatous plaque, and plasma is discussed. The results provide evidence for an effective mechanism of tissue uptake and turnover of linoleic acid. Reduced plasma levels of this acid are compensated by release from adipose tissue and atheromatous plaque. While alpha-linolenic acid is continuously taken up by the plaque, adipose tissue absorbs this acid to a certain level only. The dynamics of exchange of arachidonic acid between adipose tissue and atheromatous plaque reflects a minor role for adipose tissue in determining plaque content of this acid, suggesting that "de novo" synthesis is the chief source of arachidonic acid in plaques.     

A frontal variant of Alzheimer's disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex

A frontal variant of Alzheimer's disease (AD) has recently been identified on neuropathological and neuropsychological grounds (Johnson, J.K., Head, E., Kim, R., Starr, A., Cotman, C.W., 1999. Clinical and pathological evidence for a frontal variant of Alzheimer Disease. Arch. Neurol. 56, 1233-1239). Frontal AD differs strikingly from typical AD by the occurrence of neurofibrillary tangle densities in the frontal cortex as high or higher than in the entorhinal cortex. Since cerebrocortical membranes are commonly abnormal in Alzheimer's disease (AD), we assayed frontal AD cases for enzymes regulating membrane phospholipid composition. We specifically measured activity of phospholipase A2s (PLA2s) in dorsolateral prefrontal and lateral temporal cortices of frontal AD cases (n=12), which have respectively high and low densities of neurofibrillary tangles. In neither cortical area was Ca(2+)-dependent PLA2 activity abnormal compared to controls (n=12). In contrast, a significant 42% decrease in Ca(2+)-independent PLA2 activity was found in the dorsolateral prefrontal, but not the lateral temporal, cortex of the frontal AD cases. Similarly, the dorsolateral prefrontal cortex, but not the lateral temporal cortex of the frontal AD cases suffered a 42% decrease in total free fatty acid content, though neither that decrease nor those in any one species of free fatty acid was significant. The observed biochemical changes probably occurred in neurons given (a) our finding that PLA2 activity of cultured human NT2 neurons is virtually all Ca(2+)-independent and (b) the finding of others that nearly all Ca(2+)-independent PLA2 in brain gray matter is neuronal. The decrease in Ca(2+)-independent PLA2 activity is not readily attributable to Group VI or VIII iPLA2s since neither NT2N neurons nor our brain homogenates were greatly inhibited by drugs potently suppressing those iPLA2s. Decreased Ca(2+)-independent PLA2 activity in frontal AD may reflect a compensatory response to pathologically accelerated phospholipid metabolism early in the disorder. That could cause an early elevation of prefrontal free fatty acids, which can stimulate polymerization of tau and thus promote the prefrontal neurofibrillary tangle formation characteristic of frontal AD.     

Proliferation of C6 glioma cells requires the phospholipid remodeling enzyme tafazzin independent of cardiolipin composition

The mitochondrial phospholipid (CL) has been linked to mitochondrial and cellular functions. It has been postulated that the composition of CL is of impact for mitochondrial energy metabolism and cell proliferation. Although a correlation between CL composition and proliferation could be demonstrated for several cell types, evidence for a causal relationship remains obscure. Here, we applied two independent approaches, i) supplementation of fatty acids and ii) knock-out of the phospholipid remodeling enzyme tafazzin, to manipulate CL composition and analyzed the response on proliferation of C6 glioma cells. Both strategies caused substantial changes in the distribution of cellular fatty acids as well as in the distribution of fatty acids incorporated in CL that were accompanied by changes of the composition of molecular CL species. These changes did not correlate with cell proliferation. However, knock-out of tafazzin caused dramatic reduction in proliferation of C6 glioma cells independent of CL composition. The mechanism of tafazzin-dependent restriction of proliferation remains unclear. Among the various fatty acids administered only palmitic acid restricted cell proliferation by induction of cell death.     

Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes.

Depression and bipolar disorder are two of the commonest illnesses in the developed world. While some patients can be treated effectively with available drugs, many do not respond, especially in the depression related to bipolar disorder. Depression is associated with diabetes, cardiovascular disease, immunological abnormalities, multiple sclerosis, cancer, osteoporosis and ageing: in each case depressed individuals have a worse outcome than non-depressed individuals. In all of these conditions there is now evidence of impaired phospholipid metabolism and impaired fatty acid-related signal transduction processes. Impaired fatty acid and phospholipid metabolism may be a primary cause of depression in many patients and may explain the interactions with other diseases. Several novel gene candidates for involvement in depression and bipolar disorder are proposed.     

Gene targets related to phospholipid and fatty acid metabolism in schizophrenia and other psychiatric disorders: an update

Phospholipids make up about 60% of the brain's dry weight and play key roles in many brain signal tranduction mechanisms. A recent review(1)identified the increasing evidence that abnormal phospholipid and related fatty acid metabolism may contribute to illnesses such as schizophrenia, bipolar disorder, depression and attention deficit hyperactivity disorder. This current paper reviews the main pathways of phospholipid metabolism, emphasizing the role of phospholipases of the A2 in signal tranduction processes. It also updates the chromosomal locations of regions likely to be involved in these disorders, and relates these to the known locations of genes directly or indirectly involved in phospholipid and fatty acid metabolism.     

Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: A common link between risk factors and coronary and peripheral vascular disease?

Although elevated levels of cholesterol are associated with increased risks of coronary and peripheral vascular disease, the association frequently fails to provide a causative explanation at the individual level. New hypotheses are required which, whether or not they are correct, will provide new lines of research. It is proposed here that the causes of vascular disease are abnormal membrane phospholipid concentrations of the 20-carbon and 22-carbon essential fatty acids (EFAs) of the n-6 and n-3 series. These levels become abnormal with ageing, with stress and in response to smoking, high cholesterol levels and high saturated fat intakes. They are also abnormal in patients with diabetes and hypertension. The effects of these EFAs and their metabolites include lowering of triglycerides, elevation of high-density lipoprotein (HDL)-cholesterol, reduction of blood pressure, vasodilatation, reduction of fibrinogen levels and inhibition of platelet aggregation and of cardiac arrhythmias. Prospective studies have shown that abnormal levels of these fatty acids are predictive of future coronary death. Controlled trials of treatment have demonstrated that provision of the fatty acids reduces both coronary and total mortality. Further experimental and clinical investigations of the roles of appropriate membrane concentrations of these fatty acids are justified.     

Dietary long-chain fatty acids and visual response in malnourished nursing infants

Polyunsaturated fatty acids (PUFAs) derived from essential fatty acids (EFAs) play an important role in prenatal visual and neural development. Protein-energy malnutrition affects PUFA supply, and hence the synthesis of structural lipids during growth. Recently, some physiological studies reported abnormalities in the visual function of formula-fed infants relative to breast-fed infants. The purpose of our study was to assess whether fatty acid composition of the malnourished infant diet modifies the visual function and erythrocyte phospholipid fatty acid composition. Three groups of full-term malnourished infants were selected. Two groups received commercial formulas. One of them supplied linoleic and alpha -linolenic acid: Formula I (FI), and the other supplied, in addition, long-chain PUFAs from n-3 and n-6 series: Formula II (FII). A reference group of breast-fed infants was also enrolled. Visual function was assessed using full-field flash electroretinography, and the erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography. Those infants receiving the supplemented formula (FII) exhibited a similar retinal function to that of breast-fed infants. However, normal results were not achieved when infants were fed on the FI formula. In all groups, the results were correlated with the proportion of docosahexaenoic acid in erythrocyte phospholipid fatty acid composition. We conclude that in malnourished infants a nutrient formula enriched with long-chain fatty acids of n-6 and n-3 series could be helpful to achieve an erythrocyte fatty acid pattern and a visual function similar to that obtained in breast-fed infants.     

Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease

Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Alzheimer's disease (AD) is a progressive disorder with cognitive and memory decline, speech loss, personality changes and synapse loss. Many approaches have been undertaken to understand AD, but the heterogeneity of the etiologic factors makes it difficult to define the clinically most important factor determining the onset and progression of the disease. However, increasing evidence indicates that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to AD pathogenesis. Brains of AD patients undergo many changes, such as disruption of protein synthesis and degradation, classically associated with the heat shock response, which is one form of stress response. Heat-shock proteins are proteins serving as molecular chaperones involved in the protection of cells from various forms of stress. Recently, the involvement of the heme oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein (APP). HO induction, which occurs together with the induction of other HSPs during various physiopathological conditions, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, represents a protective system potentially active against brain oxidative injury. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Recently, increasing interest has been focused on identifying dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiological events underlying AD pathology. Alzheimer's disease, in fact, involves a chronic inflammatory response associated with both brain injury and beta-amyloid associated pathology. Spice and herbs contain phenolic substances with potent antioxidative and chemopreventive properties, and it is generally assumed that the phenol moiety is responsible for the antioxidant activity. In particular, curcumin, a powerful antioxidant derived from the curry spice turmeric, has emerged as a strong inducer of the heat shock response. In light of this finding, curcumin supplementation has been recently considered as an alternative, nutritional approach to reduce oxidative damage and amyloid pathology associated with AD. Here we review the importance of the heme oxygenase pathway in brain stress tolerance and its significance as antidegenerative mechanism operating in AD pathogenesis. We also discuss the role that exogenous antioxidant supplementation, conceivably, could play in AD in combating oxidative damage and compensating for the decreased level of endogenous antioxidants. Conceivably, dietary supplementation with vitamin E or with polyphenolic agents, such as curcumin and its derivatives, can forestall the development of AD, consistent with a major "metabolic" component to this disorder. Such an outcome would provide optimism that the signs and symptoms of this devastating brain disorder of aging may be largely delayed and/or modulated.     

Δ6-Desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids

Mammalian cell viability is dependent on the supply of the essential fatty acids (EFAs) linoleic and α-linolenic acid. EFAs are converted into ω3- and ω6-polyunsaturated fatty acids (PUFAs), which are essential constituents of membrane phospholipids and precursors of eicosanoids, anandamide and docosanoids. Whether EFAs, PUFAs and eicosanoids are essential for cell viability has remained elusive. Here, we show that deletion of Δ6-fatty acid desaturase (FADS2) gene expression in the mouse abolishes the initial step in the enzymatic cascade of PUFA synthesis. The lack of PUFAs and eicosanoids does not impair the normal viability and lifespan of male and female fads2−/− mice, but causes sterility. We further provide the molecular evidence for a pivotal role of PUFA-substituted membrane phospholipids in Sertoli cell polarity and blood–testis barrier, and the gap junction network between granulosa cells of ovarian follicles. The fads2−/− mouse is an auxotrophic mutant. It is anticipated that FADS2 will become a major focus in membrane, haemostasis, inflammation and atherosclerosis research.     

Towards a whole-body systems [multi-organ] lipidomics in Alzheimer's disease

Preclinical and clinical evidence suggests that docosahexaenoic acid (DHA), an omega-3 fatty acid derived from diet or synthesized in the liver, decreases the risk of developing Alzheimer’s disease (AD). DHA levels are reduced in the brain of subjects with AD, but it is still unclear whether human dementias are associated with dysregulations of DHA metabolism. A systems biological view of omega-3 fatty acid metabolism offered unexpected insights on the regulation of DHA homeostasis in AD [1]. Results of multi-organ lipidomic analyses were integrated with clinical and gene-expression data sets to develop testable hypotheses on the functional significance of lipid abnormalities observed and on their possible mechanistic bases. One surprising outcome of this integrative approach was the discovery that the liver of AD patients has a limited capacity to convert shorter chain omega-3 fatty acids into DHA due to a deficit in the peroxisomal d-bifunctional protein. This deficit may contribute to the decrease in brain DHA levels and contribute to cognitive impairment.     

Detrimental effect of eicosapentaenoic acid supplementation on bone following ovariectomy in rats

Although several studies have reported a positive effect of n-3 essential fatty acids (EFAs) on bone density post-ovariectomy, the role of specific EFAs has yet to be fully elucidated. In this study, ovariectomised (OVX) rats were supplemented with 0.1 g (LOW) or 1.0 g (HIGH) of eicosapentaenoic acid (EPA)/kg body weight for 9 weeks. Bone mineral density (BMD), 25-hydroxyvitamin D(3) and plasma fatty acid profile were compared to those of OVX and sham animals fed a non-supplemented diet. BMD decreased significantly in all OVX (P<0.001) but not sham rats. There was no difference in BMD between the LOW group and OVX controls. BMD was significantly lower in the HIGH group compared to OVX and sham controls. 25-hydroxyvitamin D(3) levels were significantly higher in both the LOW and HIGH groups compared to OVX controls (P=0.0006 and 0.02, respectively). In conclusion, high-dose EPA supplementation exacerbated the effects of ovariectomy on BMD.