Choline Phosphoglycerides Research Articles

Dimethyl acetals, an indirect marker of the endogenous antioxidant plasmalogen level, are reduced in blood lipids of Sudanese pre-eclamptic subjects whose background diet is high in carbohydrate

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Dietary inclusion of salmon, herring and pompano as oily fish reduces CVD risk markers in dyslipidaemic middle-aged and elderly Chinese women

Dietary intervention studies to assess the cardioprotective effects of oily fish are scarce in China. The present study aimed to examine the effects of the oily fish, Norwegian salmon, herring and local farmed pompano (Trachinotus ovatus) on CVD risk markers when included in the Chinese diet. In this 8-week, parallel-arm, randomised intervention study, 126 Chinese women with hypertriacylglycerolaemia, aged 35-70 years, were assigned to four groups to consume an experimental lunch containing 80 g fillets of either one of three oily fish or a mix of commonly eaten meats (pork/chicken/beef/lean fish) for 5 d/week. The results showed that inclusion of the three oily fish significantly increased the intake of n-3 long-chain PUFA (LC-PUFA) while decreasing the dietary n-6:n-3 PUFA ratio. Compared to the control group, significant increases of DHA, EPA+DHA and total n-3 PUFA in plasma choline phosphoglyceride were observed in the three oily fish groups. Plasma TAG levels were significantly reduced only in the salmon and herring groups. When compared to the baseline level, the three oily fish diets significantly decreased serum concentrations of TAG, apoB, apoCII and apoCIII, but only the salmon and herring diets significantly lowered TNF-α and raised adiponectin levels in serum. The salmon diet additionally decreased the serum concentration of IL-6. To conclude, dietary inclusion of salmon, herring and pompano as oily fish can effectively increase serum n-3 LC-PUFA content and are associated with favourable biochemical changes in dyslipidaemic middle-aged and elderly Chinese women, and these beneficial effects are mainly associated with n-3 LC-PUFA contents.

Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n = 19) and HU-untreated (n = 17) sickle cell patients and controls (n = 20). The HU-treated compared with the HU-untreated patients had lower arachidonic (AA) acid level in ethanolamine, physphoglycerids (EPG) (22.9 ± 1.2 versus 24.0 ± 1.1%, P < 0.05) serine SPG (22.13 ± 2.2 versus 24.9 ± 2.3%, P < 0.01) phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA) and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the untreated group had significantly (P < 0.05) lower DHA and total n-3 compared with the controls in EPG (2.7 ± 0.4 versus 3.2 ± 0.6% and 4.6 ± 0.5 versus 5.2 ± 0.7%) and CPG (0.7 ± 0.2 versus 1.0 ± 0.2% and 1.2 ± 0.2 versus 1.4 ± 0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

The fatty acid composition of the major phosphoglycerides of ram and human spermatozoa.

The major individual phosphoglycerides of ram spermatozoa have specific fatty acid compositions, whereas human spermatozoan phosphoglycerides contain a similar pattern of fatty acids. The difference in the polyunsaturated:saturated fatty acid ratio of the spermatozoan phosphoglycerides between the two species were associated with the very high polyunsaturated fatty acid content of ram spermatozoan plasmalogens. The major unsaturated fatty acid of ram spermatozoa phospholipids, docosahexaenoic acid, was concentrated in the choline phosphoglycerides, whereas the chief saturates of ram and human spermatozoa, and docosahexaenoic acid in the latter, were largely located in the choline and ethanolamine diacylphosphoglycerides.

Cerebrospinal fluid phospholipids. Quantitative determination of fractionated phospholipids and normal values in the cerebrospinal fluid.

Cerebrospinal fluid (CSF) lipids were extracted, subjected to thin-layer chromatography and quantitative determination of total and fractionated phospholipids. The methods were tested by analysis of serum and CSF pools. In CSF, sphingomyelin, choline phosphoglyceride and ethanolamine phosphoglyceride were isolated and quantitated while in serum further lyso-choline phosphoglyceride was determined. In a “normal” material of 46 patients, with disorders which were not thought to influence the composition of CSF, the total phospholipid phosphorus concentration averaged 168 μMg per 1 CSF. Sphingomyelin, choline phosphoglyceride, and ethanolamine phosphoglyceride accounted for 25, 70 and 5 per cent respectively. The sum of the fractions comprised 93 per cent of total phospholipid phosphorus found. Grouping according to sex and age did not reveal significant differences. A significant correlation was present between CSF phospholipid and protein concentrations.

Cerebrospinal fluid cholesterols and phospholipids in phenylketonuria.

Cerebrospinal fluid (CSF) cholesterols and phospholipids were fractionated and quantitated in 64 patients with phenylketonuria (PKU). In 56 patients the results were related to clinical neurological signs and to the intellectual deficiency. PKU patients had decreased mean concentrations of esterified cholesterol, total phospholipid, sphingomyelin, and choline phosphoglyceride, and increased concentration of ethanolamine phosphoglyceride. The cholesterol but not phospholipid concentrations were significantly correlated to CSF protein concentrations. Decreased cholesterol and phospholipid concentrations were predominantly seen in patients with abnormal motor signs, and the decrease was greatest in the most affected patients. There was no relation between reduced CSF lipid concentrations and the occurrence of epilepsy or the degree of mental deficiency. The reduction of CSF cholesterol and phospholipid concentrations is probably related to myelin abnormalities, and the different results observed in relation to the neurological abnormalities and to the mental deficiency point to a difference in the pathogenesis of these disorders.

Cerebrospinal fluid cholesterols and phospholipids in multiple sclerosis.

Lipids were extracted from cerebrospinal fluid (CSF) samples from 46 patients with multiple sclerosis (MS). Unesterified and esterified cholesterol, total phospholipid, sphingomyelin, choline phosphoglyceride, and ethanolamine phosphoglyceride were separated by thin layer chromatography and determined quantitatively. CSF cholesterol and phospholipid concentrations were correlated with CSF protein concentrations. The mean concentrations of phospholipids were decreased in MS. The relative concentration of esterified cholesterol was increased and that of ethanolamine phosphoglyceride decreased in this disease. Low concentrations predominated in patients with latent probable MS and in patients with slight or no disability. Patients with a recent exacerbation of symptoms and the most severely disabled patients showed a relative increase of esterified cholesterol and a decrease of ethanolamine phosphoglyceride, but these findings were not significant. It is discussed, whether these alterations may be a CSF reflection of changes of CNS lipid composition and metabolism in MS. From a clinical point of view, the determination of CSF cholesterol and phospholipid concentrations seems to be of little help due to the great variation in the concentrations in normal persons and in patients with MS.

Patients with Sickle Cell Disease have Reduced Blood Antioxidant Protection

In previous studies, we found that homozygous sickle cell (HbSS) patients, compared with their healthy (HbAA) counterparts, had reduced levels of the omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, in red cells, platelets, and mononuclear cells. These differences were not due to lower intake of the two fatty acids. We have investigated whether reduced antioxidant status in the patients could help explain the observed phenomenon. Blood specimens previously obtained for fatty acid study from Nigerian (26 HbSS and 30 HbAA) and British (30 HbSS, 9 sickle cell-hemoglobin C/HbSC, and 15 HbAA) subjects were analyzed for antioxidant status. The Nigerian HbSS patients compared with the controls had lower plasma retinol, alpha-tocopherol, and beta-carotene concentrations (p < 0.005) and reduced activity of red cell Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (p < 0.05). Similarly, the British HbSS group had reduced concentrations of plasma alpha-tocopherol (p < 0.005), and activities of red cell Cu/Zn-superoxide dismutase (p < 0.05) and Se-glutathione peroxidase (Se-GPx) (p < 0.005) than the controls. In addition, the British patients in comparison with those who had HbSC, a mild form of the disease, had lower alpha-tocopherol than that of the HbAA controls (p < 0.005). In the British sickle cell patients, there was a positive correlation between red cell ethanolamine phosphoglyceride (EPG) DHA and Cu/Zn-SOD activity (r = 0.700, p < 0.05), choline phosphoglyceride (CPG) DHA and Se-GPx activity (r = 0.605, p < 0.05), and CPG EPA and Se-GPx activity (r = 0.558, p > 0.05). Similarly, the percent DHA in red cell EPG was positively related with the activity of Se-GPx in the patients with HbSC (r = 0.674, p < 0.05). These findings suggest that the lower levels of membrane EPA and DHA in blood cells of the HbSS patients could be due to peroxidation resulting from a compromised antioxidant competence.

Aquatic Food Consumption, Blood Docosahexaenoic Acid and Chronic Diseases in Chinese Rural Populations

An epidemiological survey of 65 rural counties (6500 subjects) in China showed that fish consumption correlated significantly with the levels of omega-3 docosahexaenoic acid (DHA) in red blood cells (RBC) (r=0.640, P<0.001), selenium (r=0.467, P<0.001) and glutathione peroxidase (r=0.333, P<0.01) in plasma. A strong inverse correlation between DHA in RBC and cardiovascular disease (CVD) was found. The strongest correlation was the combination of DHA and oleic acid. RBC DHA itself also correlated negatively and significantly with most chronic diseases and appeared to be more protective than other omega-3 fatty acids. In a follow-up study, three regions (coastal, fresh-water and inland) were selected to examine the effects of contrasting diets in pregnancy and lactation. The plasma choline phosphoglyceride (CPG) DHA was not significantly different in the coastal and fresh-water areas but both were greater than found inland. A similar difference was found in the colostrum. These results demonstrate (i) Consumption of fresh-water fish has nearly the same effects on blood and colostrum omega-3 status as consumption of marine foods (ii) The lower DHA level of inland pregnant women is consistent with the higher incidence of CVD and other chronic diseases found in the 65 counties study in China.

Postnatal development of phospholipids and their fatty acid profile in rat heart

The aim of this study was to determine the concentration of phospholipids (PL), plasmalogen components of choline (PC) and ethanolamine (PE) phosphoglycerides (PLPC, PLPE) and fatty acid profile of PL and triacylglycerols (TAG) in developing rat left ventricular myocardium between postnatal day (d) 2 and 100. The steepest increase of total PL (TPL) concentration occurs between d2 and d5, followed by a further slower increase between d20 and d40. Similar developmental changes were observed in PC and PE. The PLPE concentration rises by d10, whereas PLPC does not change during the whole period investigated, except for the transient decline on d5. The concentration of diphosphatidylglycerol (DPG) increases by d60; the steepest rise occurs between d20 and d40. Phosphatidylinositol (PI) concentration rises only by d5. The concentration of phosphatidylserine (PS) decreases between d5 and d10 and then it does not change. Sphingomyelin (SM) concentration is maintained till d10, it declines on d20 and does not change thereafter. The proportion of saturated fatty acids (SFA) increases by d5 in PC, PE, PS and TAG, and by d10 in DPG and PI. After d20 the SFA proportion gradually decline in all lipids. Monounsaturated FA (MUFA) proportion decreases in PC, PE, PI and PS from d2 till d10, and in the weaning period it tends to rise again. In contrast, in DPG and TAG the proportion of MUFA declines during the whole postnatal period. N-6 polyunsaturated FA (PUFA) decrease in all PL by d20 and rise again thereafter; in TAG they decline between d2 and d10 and return to the initial level by d100. N-3 PUFA increase in all PL during the suckling period and decline after weaning; in TAG they increase only by d5 and then they decline. This remodeling of myocardial PL and TAG composition during postnatal development may affect membrane properties and contribute to developmental changes in the function of membrane proteins and cell signaling.

Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids

In previous studies, we reported that neonates of women with gestational diabetes mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA and DHA are selectively transferred from maternal to fetal circulation by the placenta, we have investigated whether the FA composition of the placenta is altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from Newham General Hospital, London. The women with GDM had higher levels of di-homo-gamma-linolenic (P < 0.05), docosatetraenoic (n-6 DTA; P< 0.0001), docosapentaenoic n-6 (P< 0.005), total n-6 (P < 0.005), docosapentaenoic (n-3 DPA; P < 0.005), and total n-3 (P < 0.01) FA, as well as higher levels of AA (P < 0.05) and DHA (P < 0.01), in placental choline phosphoglycerides (CPG) compared with the healthy women who served as controls. Similarly, the women with GDM had elevated n-6 DTA (P < 0.005), AA, total n-6 metabolites (P < 0.05), DHA, total n-3 metabolites, and total n-3 FA (P < 0.005) in ethanolamine phosphoglycerides (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had higher linoleic acid (P< 0.05) and lower AA, n-6 metabolites, and n-3 DPA (P < 0.01). The placenta is devoid of desaturase activity, and it is thought to be reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels of the two FA in the placenta of the GDM group suggests that these FA are taken up from the maternal circulation and retained after esterification into phosphoglycerides instead of being transferred to the fetus. Further study is needed to elucidate the mechanism involved and the effect of the phenomenon on postnatal growth and development of the offspring.

Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic and eicosapentaenoic acids

The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause of non-remediable blindness and visual impairment, is not well understood. Nevertheless, increased intraocular pressure, and vascular factors such as ocular blood flow deficits are thought to be risk factors. There is evidence of decreased optic nerve blood velocity and increased red blood cell aggregability in POAG. These factors are influenced by fatty acids. We have investigated if glaucoma patients have abnormal blood fatty acid composition. Patients with POAG ( n = 10 ) and their healthy siblings ( n = 8 ) were enrolled. Compared with their healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA, P < 0.01 ), and docosahexaenoic (DHA, P < 0.05 ) fatty acids and total ω3 long-chain polyunsaturated fatty acids (LCPUFA) ( P < 0.05 ) in red cell choline phosphoglycerides (CPG); decreased EPA ( P < 0.05 ) in ethanolamine phosphoglycerides (EPG); lower EPA ( P < 0.05 ) and total ω3 LCPUFA ( P < 0.05 ) in serine phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total ω3 LCPUFA in plasma CPG ( P < 0.005 ) and triglycerides ( P < 0.05 ) . These findings may be significant, since EPA and DHA could modulate impaired systemic microcirculation and ocular blood flow and optic neuropathy, which are the main physiological changes associated with glaucoma.

Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance

Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Abnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS)

Sickle cell disease (SCD) is a group of inherited blood disorders in which clinical illness results from the presence of erythrocytes with sickled haemoglobin (HbS). Blood vessel occlusion is a fundamental pathological process in SCD. Sickle cell haemoglobin C (HbSC) disease and sickle cell anaemia (HbSS) share some pathophysiology and clinical manifestations. However, the former is generally less severe. Erythrocytes of HbSC patients have longer life span, reduced haemolysis, and lower propensity to adhere to vascular endothelium than those of their HbSS counterparts. The structure and function of erythrocytes are strongly modulated by membrane long chain polyunsaturated fatty acids (LCPUFA). We have tested the possibility that HbSC and HbSS patients have different membrane fatty acid composition consistent with the difference in their clinical severity. Steady-state patients, 9 HbSC and 28 HbSS, and 15 HbAA were studied. The HbSC patients had a higher level of linoleic (LA, P < 0.05 ) and docosahexaenoic (DHA, P < 0.05 ) acids, and lower arachidonic acid (AA, P < 0.01 ) and AA/eicosapentaenoic acid (EPA) ratio ( P < 0.05 ) in erythrocyte choline phosphoglycerides (CPG) compared with the HbSS group. Similarly, the level of EPA was higher and AA/EPA ratio ( P < 0.01 ) lower in serine phosphoglycerides of the HbSC patients. In contrast to the HbSC, the HbSS group had lower levels of EPA ( P < 0.001 ) , DHA ( P < 0.05 ) , total n-3 metabolites and total n-3 fatty acids ( P < 0.001 ) in erythrocyte CPG compared with the healthy HbAA controls. Moreover, the HbSS patients with disease complications compared with those without complications had reduced DHA and total n-3 fatty acids ( P < 0.005 ) in erythrocyte CPG. The abnormalities in erythrocyte in LCPUFA which is manifested by an increase in AA and a decrease in EPA and DHA in HbSS relative to HbSC disease observed in this study are consistent with the contrast in clinical severity between the two entities.

Blood Lipid Abnormalities in Sickle Cell Disease Are Pancellular and Clinically Important.

In a previous study, we observed that high expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocyte membranes is associated with severe sickle cell disease (Eur J Haem. 2002; 69: 135– 144). The lipid composition of cell membranes affects adhesion molecule expression, cell integrity and function (Calder P Lipids. 2003; 38: 343–352). Omega-3 fatty acids (FA) such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) are vital for the structure and function of cell membranes. Sickling perturbs the normal asymmetry of erythrocyte membrane lipids. Choline phosphoglycerides (CPG) move from the outer to inner leaflet. Ethanolamine (EPG) and serine (SPG) phosphoglycerides shift from the inner to the outer layer. Exposure of the highly reactive SPG to plasma promotes clotting, rbc adhesion to vascular endothelium, wbcs and platelets; vaso-occlusion, and ischaemic organ damage. Loss of lipid asymmetry impairs the structure of rbc membranes, causes abnormal ion flux and exacerbates haemolysis. Although rbc and plasma lipid abnormalities are recognised, there is little data on occurrence and clinical relevance of leukocyte or platelet FA anomalies in SCD. The aim of this study is to find out if the FA constitution of blood cell membranes modulates the clinical features of SCD. The FA composition of blood cells and plasma was analysed in 68 HbSS and 9 HbSC patients in steady-state (40M, 37F, age 11–52 yr, mean 26 yr); and 58 healthy, age, sex and race matched HbAA controls from the same environment. We excluded cigarette smokers, anyone who had blood transfusion or pregnancy in the previous 4 months, and SCD patients with co-morbidities or HbF ≥ 10%. Steady-state Hb level in HbSS patients showed highly significant positive correlation with the proportions of DHA in erythrocyte membrane CPG (p<0.001, r = 0.42); and of EPA in membrane EPG (p<0.01, r = 0.57). There was very significant reduction of red cell and plasma EPA of HbSS patients compared to HbSC and HbAA individuals (p<0.001). Similarly, DHA and EPA were significantly reduced in leukocytes and platelets of HbSS patients relative to controls (p<0.005). Compared to HbSS patients who had no complications of SCD (n=9), those with complications (n=19) had markedly reduced DHA and total omega-3 fatty acids in erythrocytes (p<0.005), and platelets (p<0.05). Since EPA and DHA are essential structural and functional components of cell membranes, and precursors of potent anti-inflammatory eicosanoids and cytokines, decrease in their proportions exacerbates haemolysis, inflammation, vaso-occlusion and organ damage in SCD. Tomer et al (Thromb. Hemost. 85; 966–974) and our group observed reduction in the number of sickle cell crisis during pilot clinical trials of EPA and DHA. The current study and pilot trials suggest that omega-3 FA therapy has considerable potential in SCD. As natural constituents of fish oil omega-3 FA are eaten safely world-wide, and are affordable in developing countries where majority of SCD patients live. Unlike hydroxyurea, they are not cytotoxic, teratogenic or immunosuppressive. Unlike regular blood transfusions, there is no risk of HIV or other infections. Omega-3 FA are beneficial in cardiovascular and multi-organ chronic inflammatory conditions. There are sufficient grounds for a large clinical trial of EPA and DHA in the multi-system disorder that is SCD.

Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine

This study was conducted to determine whether dietary ganglioside (GG) increases the content of ether phospholipids (EPL) in intestinal mucosa. Weanling Sprague-Dawley rats were fed a semipurified diet consisting of 20% fat as a control diet. Two experimental diets were formulated by adding either 0.1% (w/w fat) GGs (GG diet) or 1.0% (w/w fat) sphingomyelin (SM diet) to the control diet. Fatty acid methyl esters from the alkenylacyl, alkylacyl and diacyl subclasses of phospholipids were measured to determine total and molecular percentage of EPL comprising the choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG) fraction. Animals fed the GG diet significantly increased total EPL content both in CPG (by 36%) and in EPG (by 66%), and the molecular percentage of EPL in CPG (by 76%) and in EPG (by 59%) compared to animals fed the control diet. Dietary GG-induced increase in EPL resulted in a higher level of polyunsaturated fatty acids (PUFA) specifically in 20:4n-6 and 22:6n-3 compared to control animals, leading to a decrease in the ratio of saturated fatty acids (SFA) to PUFA both in CPG and in EPG. Feeding animals the SM diet showed a higher level of EPL than control animals with a concomitant increase in 22:6n-3 in EPL. The present data demonstrate that dietary GG increases the content and composition of EPL containing PUFA in the weanling rat intestine.

Plasma fatty acids of neonates born to mothers with and without gestational diabetes

Women with gestational diabetes mellitus (GDM) and their neonates have lower levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes. It is not clear if this abnormality is restricted to red cells or is a generalised problem. We have investigated plasma fatty acids of neonates (venous cord) of GDM ( n = 37 ), and non-diabetic ( n = 31 ) women. The GDMs had lower levels of dihomogamma-linolenic (20:3n-6, DHGLA) acid, ∑n-6 metabolites, DHA and ∑n-3 metabolites ( p < 0.05 ) in choline phosphoglycerides (CPG). They also had lower levels of AA (−4.5%), adrenic acid (22:4n-6, −13%), osbond acid (22:5n-6, −7%) and ∑n-6 (−2.5%). There was a similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a marker of generalised shortage of derived and parent essential fatty acids, was higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced in CPG (−4.5%), TG (−63%) and CE (−75%) of the GDM group. These findings, which are consistent with the previous red cell data, suggest that the neuro-visual and vascular development and function of the offspring of GDM women may be adversely affected if the levels of AA and DHA are compromised further by other factors, pre- or post-natally. Studies are required to elucidate the underlying mechanism for the reduction of the two fatty acids and to evaluate the developmental and health implications.

Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease

Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules alphaMbeta2 integrin and L-selectin in HbSS individuals with severe disease. Since membrane n-6 and n-3 polyunsaturated fatty acids modulate cell adhesion, inflammation, aggregation and vascular tone, we investigated the fatty acid composition of mononuclear cells (MNC) and platelets of HbSS patients in steady state (n=28) and racially matched, healthy HbAA controls with similar age and sex distribution living in the same environment (n=13). MNC phospholipids of the patients had lower levels of docosahexaenoic acid (DHA, p<0.01) and increased arachidonic acid (AA, p<0.005) relative to HbAA controls. Similarly, platelets from HbSS patients had less eicosapentaenoic acid (EPA, p<0.05) and more AA (p<0.05) in choline phosphoglycerides (CPG), with reduced DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in SCD patients with complications compared to those without (p<0.05). Reduced cell content of EPA and DHA relative to AA favours the production of aggregatory and proinflammatory eicosanoids that activate leukocytes and platelets. This facilitates inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.

Phosphatidylcholine and lysophosphatidylcholine excretion is increased in children with cystic fibrosis and is associated with plasma homocysteine, S -adenosylhomocysteine, and S -adenosylmethionine 1–3

Hepatic steatosis and fat malabsorption are common in cystic fibrosis (CF). Choline deficiency results in decreased phosphatidylcholine synthesis through the cytidine diphosphocholine-choline pathway and hepatic steatosis and in increased synthesis of phosphatidylcholine from phosphatidylethanolamine using methyl groups from S-adenosylmethionine. The intestinal absorption of phosphatidylcholine in CF is unknown. The objective was to determine whether excretion of choline phosphoglyceride (phosphatidylcholine and lysophosphatidylcholine) is increased in CF and whether loss of fecal choline phosphoglyceride is associated with altered plasma methionine cycle metabolites. A cross-sectional study involved 53 children with CF and 18 control children without CF. Blood was collected from all participants. A subset of 18 children with CF and 8 control children provided 72-h fecal samples and 5-d food records. Fat absorption was significantly lower (x+/- SEM: 86.2 +/- 1.6% and 94.1 +/- 1.2%) and excretion of fecal fat (12.9 +/- 1.7 and 3.9 +/- 0.7 g/d), phospholipid (median: 130 and 47.7 mg/d), phosphatidylcholine (19.6 and 2.1 mg/d), and lysophosphatidylcholine (60.3 and 16.9 mg/d) was significantly higher in children with CF than in control children, respectively (P < 0.05). Choline phosphoglyceride excretion was positively correlated with plasma homocysteine and S-adenosylhomocysteine and inversely related with plasma methionine (P < 0.05). Choline phosphoglyceride excretion is increased in children with CF and is associated with decreased plasma methionine and increased homocysteine and S-adenosylhomocysteine. These findings suggest choline depletion and an increased choline synthesis by S-adenosylmethionine-dependent methylation in CF, as well as a metabolic link between phosphatidylcholine metabolism and the methionine-homocysteine cycle in humans.

Blood Mononuclear Cells and Platelets Have Abnormal Fatty Acid Composition in Homozygous Sickle Cell Disease.

Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules αMβ2 integrin and L-selectin in HbSS individuals with severe disease. The n-6 and n-3 polyunsaturated fatty acids (FA) are vital structural and functional components of cell and sub-cellular membranes. They modulate cell adhesion, inflammation, aggregation and vascular tone. We investigated the FA composition of mononuclear cells (MNC) and platelets of HbSS patients in steady-state (n = 28); and racially matched, healthy HbAA controls (n = 13). MNC phospholipids of the patients had low levels of docosahexanoic acid (DHA, p<0.01), n-3 metabolites (p<0.05) and total n-3 polyunsaturated FA (p<0.05); table 1. In contrast, arachidonic (AA, p<0.005), AA:DHA ratio (p<0.005, fig 1) and total n-6 metabolites (p<0.05) were increased in the patients. Similarly, platelets from HbSS patients had low levels of eicosapentanoic acid (EPA, p<0.05), and raised AA (p<0.05) in choline phosphoglycerides (CPG); with reduced linoleic acid (LA, p<0.005) and DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in HbSS individuals with complications of SCD compared to those who had no complications (p<0.05, fig.2). Reduced EPA and DHA relative to AA favours the production of aggregatory and pro-inflmmatory eicosanoids that activate leukocytes and platelets. This may lead to enhanced inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.Table 1: Fatty Acid Composition of MNC Total Phospholipids in HbSS Patients and HbAA ControlsFatty AcidsHbSS PatientsHbAA Controls24:00.71 [0.30]***1.3 [0.4]saturates ∑38.2 [3.6]39.1 [1.7]16:10.69 [0.45]0.56 [0.11]18:114.4 [1.8]*12.9 [1.9]24:11.2 [0.3]1.1 [0.4]∑monoenes16.2 [2.1]**14.3 [1.4]18:2n-66.1 [0.9]7.0 [1.4]18:3n-60.11 [0.04]*0.23 [0.17]20:2n-60.56 [0.18]**0.83 [0.32]20:3n-6 (DHGLA)1.2 [0.2]*1.4 [0.2]20:4n-620.2 [1.7]***18.1 [1.8]22:4n-61.7 [0.4]1.6 [0.4]22:5n-60.3 [0.21]0.24 [0.14]n-6 metabolites ∑24.1 [1.9]*22.6 [1.7]n-6 ∑30.2 [2.0]29.7 [2.2]20:5n-3 (EPA)0.43 [0.16]0.61 [0.35]22:6n-3 (DHA)1.9 [0.4]**2.5 [0.6]∑n-3metabolites4.3 [0.9]*4.8 [0.4]n-3 ∑4.5 [0.9]*5.0 [0.4]DHGLA:AA ratio0.06 [0.01]****0.08 [0.01]AA:EPA ratio52.4 [20.9]38.6 [18.4]Values are Means [SD}. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001 [Display omitted] [Display omitted]