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Maternal and neonatal essential fatty acid status in phospholipids: an international comparative study.

OBJECTIVE: To investigate whether the steady decline in the maternal essential fatty acids (EFA) status during pregnancy observed in Dutch pregnant women is a local or general phenomenon. DESIGN: The EFA status was measured during uncomplicated, singleton pregnancy of healthy women from the Netherlands, Hungary, Finland, England and Ecuador. In addition, the EFA status of their neonates were measured at birth. Fatty acid profiles were analyzed in phospholipids isolated from maternal plasma and from umbilical plasma and cord vessel walls. RESULTS: Considerable differences between these centers were observed in the maternal EFA levels and EFA status indexes. However, the change in the absolute as well as relative amounts of the EFAs followed a similar course in the five populations during pregnancy. The neonatal EFA profiles reflected the differences found in maternal plasma during pregnancy and shortly after delivery. Comparable correlations were found, particularly, between the neonatal and the maternal n-3 fatty acids in the participating groups. CONCLUSIONS: It seems that the reduction in maternal EFA status during pregnancy is a general phenomenon, and is largely independent of differences in dietary habits and ethnic origin. Since the lowest values for certain maternal EFAs in a given country were significantly higher than the highest value of these EFAs throughout pregnancy in other countries, the functional implications of the pregnancy-associated reduction in the maternal EFA status for the fetal and neonatal development is not obvious and needs to be further elucidated.

Adult↗

The essential fatty acid deficient chicken as a model for cystic fibrosis.

The essential fatty acid deficient (EFAD) chicken was evaluated as a model for cystic fibrosis (CF). Three semipurified diets--(I) 1% hydrogenated coconut oil (HCO), (II) 10% soybean oil + 1% HCO, and (III) 11% HCO--were fed to chickens from hatching to 5, 8, or 11 wk. Groups I and III exhibited poor weight gain and abnormal serum fatty acid patterns characteristic of EFAD. Production of prostaglandin F2 alpha, thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin E in lung was significantly reduced at 5, 8, and 11 wk in both EFAD groups. Histopathologic examination revealed increased peribronchiolitis in group I compared with II. Incidence of pulmonary lesions in group III was intermediate. These data support the theory that essential fatty acids are necessary to maintain proper lung function. In this respect, the chicken is a good model for studying the relationship between EFAD and pulmonary disease in CF patients.

6-Ketoprostaglandin F1 alpha↗

Absorption and metabolism of [3H]arachidonic and [14C]linoleic acid in essential fatty acid-deficient rats.

[3H]arachidonic acid (20:4) and [14C]linoleic acid (18:2) were fed in a triolein emulsion to essential fatty acid-deficient (EFAD) rats and to age-matched controls. Tissues were analyzed for radioactivity of different lipid classes after 1, 2, and 4 h. As in earlier studies [Nilsson and Melin. Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 19): G612-G618, 1988], control rats retained more [3H]20:4 than [14C]18:2 in all organs except adipose tissue. In EFAD rats, recovery of [14C]18:2 was increased in small intestine, liver, heart, and kidneys. In comparison to controls, EFAD rats retained much more [14C]18:2 in phospholipids of these organs. The increase in the incorporation of both 3H and 14C into phosphatidylethanolamine was particularly pronounced. Another striking feature was the drastic increase in the retention after 4 h of 14C in cardiolipin, which is specifically located in the inner mitochondrial membrane. In contrast, incorporation of both 3H and 14C into phosphatidylinositol was decreased or unchanged in EFAD rats. Although fecal fat excretion was increased there was no evidence for a malabsorption or an increased retention in intestinal triacyglycerol of the radioactive fatty acids in EFAD rats. The proportion of [14C]18:2 that had been converted to [14C]20:4 was generally low but increased significantly with time in the liver and intestine of EFAD rats.

Aging↗

Essential fatty acid supplementation in chronic hepatitis B.

BACKGROUND: Dietary supplementation with essential fatty acids and polyunsaturated lecithin may improve biochemical and histological parameters in liver disease. METHODS: Ten patients with serological and histological evidence of chronic hepatitis B received capsules of the polyunsaturated fatty acid-rich evening primrose oil in a dose of 4 g daily for 12 months, while a matched group received liquid paraffin capsules as a placebo. RESULTS: Compared to the placebo group, the patients receiving evening primrose oil showed no improvement in either biochemical or histological indices of liver damage, or in the rate of loss of circulating e antigen. CONCLUSIONS: Dietary, supplementation with this dose of essential fatty acids is unlikely to be of benefit in chronic hepatitis B.

Adult↗

The role of essential fatty acids in development.

The presence of docosahexaenoic acid (DHA) and arachidonic acid (ARA) in human milk but not in infant formula, coupled with lower plasma and brain lipid contents of DHA in formula-fed than in breast-fed infants and reports of higher IQ in individuals who were breast-fed versus formula-fed as infants, suggest that exogenous DHA (and ARA) may be essential for optimal development. Thus, since 1990, several studies have examined the impact of formulas containing DHA or DHA plus ARA on visual function and neurodevelopmental outcome. Some of these studies have shown benefits but others have not. These results leave largely unanswered the question of whether these fatty acids are beneficial for either the term or preterm infant. However, evidence that preterm infants might benefit is somewhat more convincing than that for term infants. Despite the limited evidence for efficacy, formulas supplemented with DHA and ARA are now available and appear to be safe.

Arachidonic Acid↗

Essential fatty acid deficiency and bone fragility in rats.

This study demonstrates the effect of essential fatty acid deficiency on the postnatal skeletal development in the rat. Four groups (n = 10) of newborn Wistar rats were fed diets containing high and low proportions of essential fatty acids in the lipid fraction until day 16 after birth. Suckled littermates were used as controls. X-ray and histological studies showed the occurrence of multiple pathological fractures of the long bones in 1-month-old rats fed a diet deprived of essential fatty acids. No effect of high (51,000 IU/100 g diet) and low (5,100 IU/100 g diet) concentrations of vitamin D2 was observed in our experiment. Thus, these data suggest the importance of essential fatty acids for bone pathology in the rat.

Animals↗

Effects of essential fatty acid deficiency and supplementation with docosahexaenoic acid (DHA; 22:6n-3) on cellular fatty acid compositions and fatty acyl desaturation in a cell culture model.

The desaturation of [1-(14)C] 18:3n-3 to docosahexaenoic acid (DHA; 22:6n-3) is enhanced in an essential fatty acid deficient cell line (EPC-EFAD) in comparison with the parent cell line (EPC) from carp. In the present study, the effects of DHA on lipid and fatty acid compositions, and the metabolism of [1-(14)C]18:3n-3 were investigated in EPC-EFAD cells in comparison with EPC cells. DHA supplementation had only relatively minor effects on lipid content and lipid class compositions in both EPC and EPC-EFAD cells, but significantly increased the amount of DHA, 22:5n-3, eicosapentaenoic acid (EPA; 20:5n-3), total n-3 polyunsaturated fatty acids (PUFA), total PUFA and saturated fatty acids in total lipid and total polar lipid in both cell lines. Retroconversion of supplemental DHA to EPA was significantly greater in EPC cells. Monounsaturated fatty acids, n-9 and n-6PUFA were all decreased in total lipid and total polar lipid in both cell lines by DHA supplementation. The incorporation of [1-(14)C]18:3n-3 was greater into EPC-EFAD compared to EPC cells but DHA had no effect on the incorporation of [1-(14)C]18:3n-3 in either cell line. In contrast, the conversion of [1-(14)C]18:3n-3 to tetraenes, pentaenes and total desaturation products was similar in the two cell lines and was significantly reduced by DHA supplementation in both cell lines. However, the production of DHA from [1-(14)C]18:3n-3 was significantly greater in EPC-EFAD cells compared to EPC cells and, whereas DHA supplementation had no effect on the production of DHA from [1-(14)C]18:3n-3 in EPC cells, DHA supplementation significantly reduced the production of DHA from [1-(14)C] 18:3n-3 in EPC-EFAD cells. Greater production of DHA in EPC-EFAD cells could be a direct result of significantly lower levels of end-product DHA in these cells' lipids compared to EPC cells. Consistent with this, the suppression of DHA production upon DHA supplementation was associated with increased cellular and membrane DHA concentrations in EPC-EFAD cells. However, an increase in cellular DHA content to similar levels failed to suppress DHA production in DHA-supplemented EPC cells. A possible explanation is that greatly increased levels of EPA, derived from retroconversion of the added DHA, acts to offset the suppression of the pathway by DHA by stimulating conversion of EPA to DHA in DHA-supplemented EPC cells.

Animals↗

Abnormal essential fatty acid levels in plasma of women with premenstrual syndrome.

Premenstrual syndrome is now recognized as a condition that probably has an endocrine or biochemical basis. However, it has proved difficult to demonstrate any consistent significant differences from normal in any parameter measured to date. We have measured essential fatty acid levels in phospholipids in plasma taken from 42 women with well-defined premenstrual syndrome. The women were not on any treatment during the cycles when samples were taken in both follicular and luteal phases. The levels of linoleic acid, the main dietary n-6 essential fatty acid, were significantly above normal, indicating no deficit of intake or absorption. In spite of this, concentrations of all metabolites of linoleic acid were significantly reduced, suggesting a defect in conversion of linoleic acid to gamma-linolenic acid. Possibly in compensation, levels of n-3 essential fatty acids were elevated. The same abnormalities were present in both follicular and luteal phases. This abnormality cannot therefore be the direct cause of the symptoms that appear in the luteal phase, but it may sensitize tissues so that they respond abnormally to normal levels of reproductive hormones.

Adult↗

Suspected faulty essential fatty acid metabolism in Sjögren-Larsson syndrome.

The aim of the present study was to examine the fatty acid patterns of plasma phospholipids, cholesteryl esters, triglycerides and free fatty acids in patients with Sjögren-Larsson syndrome in order to detect whether absorption or metabolism is essential fatty acids may be abnormal. The fatty acid patterns were analyzed by gas liquid chromatography. The proportions of 23 fatty acids were calculated. The parameters used for assessment of the essential fatty acid metabolic status were calculated and compared with those from a group of institutionalized mentally retarded patients and from a group of healthy controls. There was no significant difference in either the fatty acid components or parameters used to evaluate the essential fatty acid metabolic study when the mentally retarded and control groups were compared. The relative concentration of linoleic acid (18:2 omega 6) in plasma phospholipids in patients with Sjögren-Larsson syndrome did not differ significantly from that of the healthy or mentally retarded controls, indicating that the Sjögren Larsson syndrome does not involve a dietary essential fatty acid deficiency or a defect in absorption of linoleate. In the phospholipids of Sjörgren-Larsson syndrome patients, the metabolites derived from linoleic acid were found to be significantly lower than in health controls, suggesting the metabolic defect. The total products of delta 6 desaturation were reduced to 3% of that in controls, whereas the products of delta 5 and delta 9 desaturation were not noticeably affected in the patients with Sjögren-Larsson syndrome. All individuals with Sjörgren-Larsson syndrome exhibited decreased products of delta 6 desaturation which also affected subsequent metabolites in the metabolite sequence.

Adolescent↗

Stratum corneum lipid function.

The stratum corneum contains a complex mixture of polar and nonpolar lipids in its intercellular spaces. These lipids, present in form of multiple lamellae, have been investigated for their role in providing the epidermal barrier to transcutaneous water loss, the selective barrier from the inside to the outside of the organism and partly the process of physiological desquamation. The composition of these lipids varies from species to species, with the body region and the degree of keratinocyte differentiation. The most undifferentiated layers of the epidermis contain typical membrane lipids, phospholipids, while more differentiated layers contain ceramides, cholesterol and free fatty acids. Essential fatty acids are essential for the maintenance of the lamellar structures and epidermal barrier function. Epidermal linoleic and arachidonic acids derive from exogenous sources. Only recently attempts have been made to elucidate the timing and regulation of epidermal fatty acid metabolism. Keratinocytes do not express a low molecular weight fatty acid binding protein like other cells active in lipid metabolism, but may employ alternative ways in fatty acid uptake and metabolism.

Basement Membrane↗

The effect of essential fatty acid deficiency on the fatty acid composition of different salivary glands and saliva in rats.

The main purpose was to compare the changes in fatty acid composition of lipids induced by essential fatty acid (EFA) deficiency in the rat submandibular, parotid and sublingual glands. Three groups of rats were fed for 28 weeks (1 week gestation, 3 weeks lactation and 24 weeks thereafter) diets containing 7% hydrogenated coconut oil (HCO) (EFA-deficient in both n-6 and n-3), 7% soybean oil (SBO) (control) and 7% safflower oil (SFO) (deficient in n-3). Rats were killed and salivary glands were dissected out. Lipids were extracted and the fatty acid composition of total lipids and phospholipids was determined by gas chromatography-mass spectrometry. The fatty-acid compositional changes indicative of an EFA deficiency, such as decreases in the levels of 18:2 n-6, along with an accumulation of 20:3 n-9, were generally observed in all the salivary glands of rats fed 7% HCO diet. In the submandibular glands, the proportions of 16:1, 18:1 n-9 and 18:1 n-7 were also higher in the HCO-fed group than in the other two groups. There were some differences in the fatty acid composition of the three glands. Total lipids of parotid gland had higher levels of 12:0 and 18:1 n-9 as compared to the other two glands. The levels of 18:0, 20:3 n-9, 20:3 n-6 and 20:4 n-6 were, however, lower in the parotid gland as compared with the other glands. In total phospholipids of rats fed SBO- and SFO-containing diets, the sublingual gland had lower levels of 18:2 n-6 and higher levels of 20:4 n-6 than the parotid or the submandibular. These differences in fatty acid composition may be related to possible differences in chain elongation/desaturation. The changes in fatty acid composition were also reflected in total lipids of plasma, liver and whole saliva of rats fed the various diets. A number of fatty acids were identified in saliva by gas chromatography-mass spectrometry.

Analysis of Variance↗

Dietary trans fatty acids affect the essential fatty-acid concentration of rat milk.

Increasing efforts have been made to determine the distribution and concentration of trans fatty acids in milk, due to the importance of lipids in infant growth and development. In general, trans fatty acid concentration of milk reflects trans fatty acid intake, but insufficient data are available to assess the effects of dietary trans fatty acids on maternal milk. Thus, controlled studies are needed to establish whether there is a dose-response relationship and whether trans fatty acids could affect the concentration of essential fatty acids (EFA), long-chain polyunsaturated fatty acids (PUFA) and the (n-6)/(n-3) ratio in milk. Three groups of six rats each were fed for 10 wk one of three diets differing in trans fatty acid concentration (Control, 0 mol/100 mol; high trans concentration (H), 14.5 mol/100 mol; very high trans concentration (VH), 30 mol/100 mol), but containing the same proportions of linoleic and alpha-linolenic acids and a ratio of 18:2(n-6)/18:3(n-3) of about 7:1. Trans fatty acids were incorporated into maternal milk in a dose-dependent manner. In addition, rats fed trans isomers had greater linoleic acid levels than controls. The proportion of alpha-linolenic acid in milk was lower in the VH group, and the (n-6)/(n-3) cis PUFA ratio in milk of the VH group was greater than that in controls. Total long-chain PUFA levels did not differ among groups. These results suggest that high intakes of trans fatty acids affect the EFA concentration but not that of long-chain PUFA of rat milk, provided that EFA are supplied in sufficient amounts.

Animals↗

[Early modification of the fatty acid composition of cardiolipins and other phospholipids in rat liver mitochondria during dietary deficiency of essential fatty acids followed by repletion].

Weaned rats (21-day old, 44 +/- 2 g) were distributed into 3 groups. The first group was raised on a laboratory diet for 7 or 20 days (control group). The second was fed a diet containing 0.07% fat for 1, 2, 3, 7 or 66 days. The third one was fed the low-fat diet for 7 days and then switched to a laboratory chow diet for 1, 2, 5 or 9 days. Cardiolipin (CL) on the one hand and other mitochondrial phospholipids taken as a whole (PLm) on the other hand were prepared from liver mitochondria and their fatty acids analysed. Polyunsaturated fatty acids in PLm (18:2 (n-6), 20:4 (n-6), 22:6 (n-3) acids) decreased abruptly during the first 3 days of fat deficiency and then remained rather stable till day 7. CL behaved in a quite different way. 18:2 (n-6) acid, the major polyunsaturated fatty acid of CL, decreased continuously between day 1 and day 7 from 79% to 33%. A value of 19.6% was reached on day 66. When deficient rats were transferred to an equilibrated diet, the fatty acid profile of PLm was rapidly restored. Major effects were already achieved during the first 24 h and a fatty acid composition identical to that of control rats was reached within 2 days. A considerably longer period (about 9 days) was necessary for CL to reach a level analogous to that of control rats. The diminution of linoleic acid in CL was brought about by increases in the levels of monoenoic acids: palmitoleic (16:1 (n-7)), oleic (18:1 (n-9)) and cis-vaccenic (18:1 (n-7)) acids which accounted for 18.0%, 17.7% and 17.9% respectively on day 7. Increases in the (n-7) monoenes remained comparatively low in PLm, which showed a sharp rise in their oleic acid content (from 3.9% to 12.7% in 3 days). The proportion of cis-vaccenic acid relative to total octadecenoic acids was decreased from 75% to 50% in CL. A similar trend, but of smaller magnitude, was also noticed in PLm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Oestrogen and essential fatty acid supplementation corrects bone loss due to ovariectomy in the female Sprague Dawley rat.

Essential fatty acid deficient animals develop osteoporosis. Eicosapentaenoic acid and gamma-linoleic acid have been reported to have positive effects on bone metabolism in both the growing male rat and the ovariectomized (OVX) female rat. These effects have been further investigated using a novel gamma-linolenic/eicosapentaenoic acid diester together with an oestrogen implant in the ovariectomized, female Sprague Dawley rat. Rats were sham-operated or ovariectomized at age 11 weeks. Two groups of OVX rats received an oestrogen implant at ovariectomy. Animals received fatty acids, linoleic acid (control) or a diester with gamma-linolenic acid and eicosapentaenoic acid as part of a semi-synthetic diet. Bone calcium content and excretion of deoxypyridinolines as marker of bone degradation were measured at 14 weeks. Oestrogen, as well as diester alone, increased calcium/femur to sham levels. Oestrogen plus diester potentiated the effect of oestrogen on bone calcium (P < 0.05 vs OVX). At the same time, oestrogen alone and the combination of oestrogen plus diester significantly reduced (P < 0.05 vs OVX) urinary deoxypyridinoline and hydroxyproline excretion. Again, the diester potentiated the effect of oestrogen. The effects of the diester alone, together with the potentiated effects of oestrogen by the essential fatty acids on osteoporosis, are novel findings.

Amino Acids↗

Acetic acid-induced colitis in normal and essential fatty acid deficient rats.

Eicosanoids and platelet-activating factor (PAF) production increases in experimental colitis. Both eicosanoids and PAF seem to arise from similar membrane phospholipids. To support both these suggestions we have investigated whether a fat-free diet, which should alter production of eicosanoids and PAF, affects experimental colitis. Essential fatty acid deficient (EFAD) rats were obtained by putting 4-week-old animals on a fat-free diet for 3 months. Experimental colitis was induced by a single intracolonic administration of 2 ml of 4% acetic acid. One to seven days later the animals were sacrificed and the colon removed to assess macroscopically and histologically intestinal damage. Eicosanoids and PAF levels were also measured in the mucosa scrapings by specific radioimmunoassay. The injury to the colon was more evident in control rats compared with EFAD rats. Besides colonic tissue of control rats showed a highly significant increase of PGE2, LTB4 and PAF, compared with levels in EFAD rats. Our results indicate that fat-free diet reduces tissue damage, and at the same time PGE2, LTB4 and PAF colonic content.

Acetates↗

Acquired essential fatty acid depletion in the remnant kidney: amelioration with U-63557A.

Previous studies have demonstrated an association between renal cortical fatty acid composition and experimental models of renal injury. The present study was designed to extend these observations to the remnant kidney and to investigate the hypothesis that increased endogenous turnover of arachidonic acid metabolites results in the depletion of progenitor fatty acids. Remnant kidney cortex demonstrated a relative reduction of the essential fatty acids, linoleate and arachidonate (20 +/- 7.2% and 11 +/- 0.3%, respectively), nine weeks after subtotal nephrectomy. In addition, the monounsaturated fatty acid, oleate, was increased (48 +/- 10.6%) while its saturated progenitor, stearate, was decreased (13 +/- 4.3%). Serial evaluation of dienoic prostanoids revealed a significant increase in the renal excretion of TXB2 in rats with remnant kidneys (27 +/- 3.0, 29 +/- 1.1, and 34 +/- 3.3 ng/day vs. 21 +/- 0.8, 20 +/- 1.5, and 22 +/- 3.3 ng/day in control rats, at 3, 6, and 9 weeks, respectively). Moreover, TXB2 excretion inversely correlated with dienoic progenitor fatty acids [18:2(n-6), r2 = 0.76; 20:4(n-6), r2 = 0.79], suggesting that these events are biochemically coupled. Endogenous turnover of precursor fatty acids, confirmed by an increase in renal TXB2 excretion, preceded overt depletion of essential fatty acids by several weeks. Importantly, blockade of endogenous synthesis of TXA2 with the specific TXA2 synthase antagonist, U-63557A, restored the essential fatty acid composition to normal and ameliorated progressive glomerular destruction. Moreover, the ancillary fatty acid disturbances were attenuated by administration of U-63557A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗