Cell Membrane Phospholipid Fatty Acid Research Articles

Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation-associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α-linolenic acid, the precursor of long chain omega-3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti-inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF-κB. However, few studies have examined the anti-neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD-like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation-mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down-regulation of proinflammatory mediators, such as inducible NOS, COX-2, IL-1β, and TNF-α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF-κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.

Omega-3 fatty acids and inflammatory processes: from molecules to man.

Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.

Identification of a novel fatty acid in the cell membrane of Chryseobacterium frigidisoli PB4T isolated from an East Antarctic glacier forefield

The cell membrane phospholipid fatty acid (PLFA) inventory of Chryseobacterium frigidisoli PB4T, a psychrotolerant, non-motile, gram-negative, aerobic bacterium isolated from ice free permafrost deposits in continental Antarctica contains a FA with a novel methyl ester mass spectrum. In a temperature cultivation experiment of C. frigidisoli at 0°C this unknown FA was the dominant PLFA. The molecular mass indicates a C17 FA with two double bond equivalents (DBEs). A 3-pyridylcarbinol derivatization experiment as well as hydrogenation of the double bonds allowed structural assignment of the respective FA as 14-methyl-hexadeca-9,13-dienoic acid (anteiso-heptadeca-9,13-dienoic acid or ai-17:2Δ9,13) an unusual anteiso-ω3-FA with bis-methylene interrupted double bonds (ai-17:2ω3,7 or ai-17:2n-3,7). The iso-counterpart of this unsaturated FA also occurred in trace amount. The close vicinity of the ω3 double bond to the anteiso branch and also to the iso branch seems to be responsible for a shift in the gas chromatography retention times of these compounds, resulting in elution shortly after the saturated counterparts. The dominance of the ai-17:2ω3,7 at 0°C cultivation temperature suggests its importance for cell membrane adaptation of C. frigidisoli with respect to low ambient temperature conditions.

Age-induced perturbation in cell membrane phospholipid fatty acid profile of longevity-selected Drosophila melanogaster and corresponding control lines

Various compositions of fatty acids can produce cell membranes with disparate fluidity and propensity for oxidation. The latter characteristic, which can be evaluated via the peroxidation index (PI), has a fundamental role in the development of the “membrane-pacemaker theory” of aging. This study tried to evaluate differences between the membrane phospholipid fatty acid (PLFA) profile of longevity-selected (L) and corresponding control (C) lines of Drosophila melanogaster with age (3, 9, 14 and 19days) and its consequences on phase transition temperature as a function of membrane fluidity. Despite an equal proportion of polyunsaturated fatty acids, PI and double bond index over all ages in both experimental groups, monounsaturated fatty acids showed significant variation with advancement of age in both L and C lines. A significant age-associated elevation of the unsaturation vs. saturation index in parallel with a gradual reduction of the mean melting point was observed in longevous flies. PLFA composition of the L vs. C lines revealed a dissimilarity in 3-day old samples, which was based on the positive loading of C14:0 and C18:3 as well as negative loading of C18:0. The findings of this study are not in agreement with the principle of the “membrane pacemaker theory” linking PI and longevity. However, the physiochemical properties of PLFAs in longevity lines may retard the cells' senescence by maintaining optimal membrane functionality over time. Identical susceptibility to peroxidation of both types of lines underlines the involvement of other mechanisms in protecting the bio-membrane against oxidation, such as the reduced production of mitochondrial reactive oxygen species or improvement of the antioxidant defense system in longer-lived phenotypes. Concurrent assessments of these mechanisms in relation to cell membrane PLFA composition may clarify the cellular basis of lifespan in this species.

Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to inhibit partly a number of aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the anti-inflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor γ) and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g day⁻¹ seems to be required to elicit anti-inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n-3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta-analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.

Maintenance of Arachidonic Acid and Evidence of Δ5 Desaturation in Cats Fed γ‐Linolenic and Linoleic Acid Enriched Diets

Cats have limited Δ6 desaturase activity. However, γ-linolenate (GLA) feeding may by-pass the Δ6 desaturase step allowing arachidonate (ARA) accumulation via Δ5-desaturation. Alternatively, high dietary linoleate (LNA) may induce limited Δ6 desaturase also resulting in ARA accumulation. Fatty acid profiles were determined after feeding high LNA, high GLA, or adequate LNA diets. Adult female cats (n=29) were assigned to one of three groups and fed for 8weeks. Plasma samples were collected at weeks 0, 2, 4 and 8 for plasma triacylglycerol (TAG), total cholesterol (TC), lipoprotein (LP), and plasma and red blood cell membrane phospholipid fatty acid determinations. Time, but no diet, effects were observed for TAG, TC, and LP fractions at weeks 2 and 4 with significant increases likely due to increased dietary fat. However, all values were within feline normal limits. The GLA diet resulted in increased dihomo-γ-linolenic acid (DGLA) and ARA as early as week 2, supporting a ∆5 desaturase. Further evidence of Δ5 desaturase was found at high dietary LNA with the appearance of a novel fatty acid, 20:3 ∆7, 11, 14, apparently formed via ∆5 desaturation and chain elongation of LNA. However, Δ6 desaturase induction at high dietary LNA concentration was not observed. Cats are able to maintain plasma and red blood cell ARA when fed a practical diet containing GLA using what appears to be an active Δ5 desaturase enzyme.

Comparing PLFA and amino sugars for microbial analysis in an Upper Michigan old growth forest

Phospholipid fatty acid (PLFA) analysis and amino sugars analysis were compared with respect to their capacity to reliably indicate microbial biomass and gross community structure (e.g. fungi to bacteria ratio). We sampled three sets of soils beneath dominant canopy-tree species in an old growth forest and extracted them using both PLFA and amino sugars procedures. Amino sugars data had a lower coefficient of variation among sample replicates and therefore may be better for quantitative application compared to PLFA data. However, when considering microbial community structure, PLFA had an advantage over amino sugars due to its more straightforward interpretation. Finally, because each biomarker derives from different portions of the microbial biomass, a conversion factor between cell membrane PLFA and cell wall amino sugars may be valuable in understanding soil carbon cycling.

Metabolic characteristics of healthy adult males as affected by ingestion of a liquid nutritional formula containing fish oil, oligosaccharides, gum arabic and antioxidant vitamins

n-3 fatty acids from fish oil and short-chain fatty acids produced from fermentation of oligosaccharides may attenuate a portion of gut injury and inflammation associated with ulcerative colitis. The purpose of this study was to assess the effects of an enteral nutritional formula containing supplemental oligosaccharides, gum arabic and fish oil on serum metabolite profiles, haematology, plasma and red blood cell membrane phospholipid fatty acid profiles, urinary constituent, and safety in healthy human adult males. 30 subjects were randomly assigned to one of two treatments, a control formula (n = 10) and an ulcerative colitis nutritional formula (UCNF; n = 20). Formulas contained comparable levels of protein, fat and non-structural carbohydrates. Daily intake of the formulas provided nutrients to meet or exceed the recommended daily allowance. Intake was recorded daily while blood and urine samples were collected weekly on days 0, 7 and 14. Certain subjects consuming large quantities of the UCNF experienced some abdominal distention, gas and loose stools. Sole source intake of the UCNF was safe over 14 days as assessed by routine measurements of serum metabolite profiles, haematology and urinalysis compared with subjects fed the control formula. Substantial decreases in plasma and red blood cell phospholipid 18:2n-6 and increases in 20:5n-3 and 22:6n-3 within 1 wk of feeding the UCNF were noted.

Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes.

In this work we have examined the effect of the oral administration of propionyl-L-carnitine (PLC) on the membrane phospholipid fatty acid turnover of erythrocytes from streptozotocin-induced diabetic rats. A statistically significant reduction in radioactive palmitate, oleate, and linoleate, but not arachidonate, incorporation into membrane phosphatidylcholine (PC) of diabetic rat erythrocytes with respect to control animals was found. Changes in radioactive fatty acid incorporation were also found in diabetic red cell phosphatidylethanolamine (PE), though they were not statistically significant. Oral propionyl-L-carnitine (PLC) treatment of diabetic rats partially restored the ability of intact red cells to reacylate membrane PC with palmitate and oleate, and reacylation with linoleate was fully restored. The analysis of the membrane phospholipid fatty acid composition revealed a consistent increase of linoleate levels in diabetic rat red cells, a modest decrease of palmitate, oleate and arachidonate. The phospholipid fatty acid composition of diabetic red blood cells was not affected by the PLC treatment. Lysophosphatidylcholine acyl-CoA transferase (LAT) specific activity measured with either palmitoyl-CoA or oleyl-CoA was significantly reduced in diabetic erythrocyte membranes in comparison to controls. In addition, LAT kinetic parameters of diabetic erythrocytes were altered. The reduced LAT activity could be partially corrected by PLC treatment of diabetic rats. Our data suggest that the impaired erythrocyte membrane physiological expression induced by the diabetic disease may be attenuated by the beneficial activity of PLC on the red cell membrane phospholipid fatty acid turnover.

Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice.

Diets rich in omega-6 polyunsaturated fatty acids (e.g., corn oil and other fats containing linoleic acid) stimulate the growth and metastasis of human breast cancer cells in athymic nude mice. On the other hand, diets containing fish oil, which is rich in omega-3 fatty acids (e.g., eicosapentaenoic and docosahexaenoic acids), exert suppressive effects. Our objective was twofold: 1) to compare the effects of diets containing linoleic acid with those of diets containing eicosapentaenoic acid and docosahexaenoic acid on the growth and metastasis of MDA-MB-435 human breast cancer cells in the nude mouse model and 2) to determine how such effects relate to observed changes in the chemical content of tumor fatty acids and eicosanoid production. Groups of 30 female athymic nude mice were fed 20% (wt/wt) fat diets containing either linoleic acid (8%) alone, linoleic acid (8%) plus eicosapentaenoic acid (4%) or docosahexaenoic acid (4%), or linoleic acid (4%) plus eicosapentaenoic acid (8%) or docosahexaenoic acid (8%) for 7 days before one million MDA-MB-435 cells were injected into a thoracic mammary fat pad. Diets were continued for 12 more weeks. Primary tumors were measured weekly. The mice were then killed and necropsied, and tumor tissues preserved. Cell membrane phospholipid fatty acid analyses and eicosanoid assays were performed. All P values represent two-tailed tests of statistical significance. The growth of the primary tumors was retarded in mice fed the diets supplemented with eicosapentaenoic or docosahexaenoic acid compared with the growth of primary tumors in mice fed the 8% linoleic acid diet. Growth inhibition was statistically significant (P < .05) and most effective in association with the diets containing 8% of either omega-3 fatty acid, where tumors were smaller than those in the group fed the diet containing 8% linoleic acid alone at all time points after the 2nd week. The occurrence and severity of lung metastases were reduced in the groups fed omega-3 fatty acid (P < .05). In groups of mice fed eicosapentaenoic or docosahexaenoic acid, the representation of these acids in tumor phospholipids increased, with a statistically significant reduction in the concentrations of arachidonic acid (all groups), tumor 12- and 15-hydroxyeicosatetraenoic acid, and prostaglandin E. Levels of 5-hydroxyeicosatetraenoic acid and leukotriene B4 were unaffected by the omega-3 fatty acids. The inhibitory effects of dietary fish oil on human breast cancer cell growth and metastasis in this model system are ascribable to its high eicosapentaenoic acid and docosahexaenoic acid content; the mechanism very likely involves suppression of tumor eicosanoid biosynthesis. Future dietary intervention trials designed to reduce the risk of recurrence in the postsurgical breast cancer patient should include the evaluation of eicosapentaenoic acid and docosahexaenoic acid supplementation.

Developmental changes in cholinephosphate cytidylyltransferase activity and microsomal phospholipid fatty acid composition in alveolar type II cells

Cholinephosphate cytidylyltransferase is the rate-limiting enzyme in the choline pathway of phosphatidylcholine synthesis in fetal and adult lung. To examine the developmental changes in cytidylyltransferase activity, subcellular fractions were prepared from freshly isolated type II cells from 19 and 21 d gestation fetal rats, newborn (0 h, 3 h, 3–12 h, +1, +2, +7 postnatal day), and adult rats and the fractions assayed for cytidylyltransferase activity. Cytidylyltransferase activity per cell was low during late fetal gestation, but rose rapidly during the first 3 h after birth, predominantly due to an increase in microsomal enzyme activity. Microsomal and cytosolic enzyme specific activity increased 6 and 3.9 fold, respectively, from birth (0 h) to +1 postnatal day. The subcellular distribution of enzyme activity changed from 40% microsomal in fetal type II cells to 85% microsomal at 3–12 h, and 60% in this compartment in adult type II cells. Although evidence suggests that membrane lipid may affect enzyme activity, developmental changes in type II cell membrane phospholipid fatty acid composition have not been previously studied. Capillary gas chromatography analysis of phospholipid fatty acids extracted from microsome fractions revealed a 3-fold increase in both total saturated and unsaturated phospholipid fatty acids from day 19 to day 21 gestation. There was a further 62% increase in total saturated fatty acids during the first postnatal day, concomitant with the peak in microsomal cytidylyltransferase activity.