EFA-deficient Diet Research Articles

Essential fatty acid deficiency in mice impairs lactose digestion

Essential fatty acid (EFA) deficiency in mice induces fat malabsorption. We previously reported indications that the underlying mechanism is located at the level of the intestinal mucosa. We have investigated the effects of EFA deficiency on small intestinal morphology and function. Mice were fed an EFA-deficient or control diet for 8 wk. A 72-h fat balance, the EFA status, and small intestinal histology were determined. Carbohydrate absorptive and digestive capacities were assessed by stable isotope methodology after administration of [U-(13)C]glucose and [1-(13)C]lactose. The mRNA expression and enzyme activity of lactase, and concentrations of the EFA linoleic acid (LA) were measured in small intestinal mucosa. Mice fed the EFA-deficient diet were markedly EFA-deficient with a profound fat malabsorption. EFA deficiency did not affect the histology or proliferative capacity of the small intestine. Blood [13C6]glucose appearance and disappearance were similar in both groups, indicating unaffected monosaccharide absorption. In contrast, blood appearance of [13C]glucose, originating from [1-(13)C]lactose, was delayed in EFA-deficient mice. EFA deficiency profoundly reduced lactase activity (-58%, P<0.01) and mRNA expression (-55%, P<0.01) in mid-small intestine. Both lactase activity and its mRNA expression strongly correlated with mucosal LA concentrations (r=0.77 and 0.79, respectively, P<0.01). EFA deficiency in mice inhibits the capacity to digest lactose but does not affect small intestinal histology. These data underscore the observation that EFA deficiency functionally impairs the small intestine, which in part may be mediated by low LA levels in the enterocytes.

M1731 Sphingosine-1-Phosphate Regulates Barrier Function in Cultured Intestinal Epithelial Cells and Murine Intestinal Tissue

assessed by stable isotope methodology after administration of U-13C-glucose and 1-13Clactose. Concentrations of the EFA linoleic acid (LA), and the enzyme activity and mRNA expression of lactase, were measured in the mucosa of proximal, mid and distal small intestine. Results: Mice fed the EFA-deficient diet were markedly EFA-deficient (triene/ tetraene ratio 0.23±0.06 vs. 0.01±0.00 in controls, p<0.05) with a profound lower fat absorption of dietary fat (81±3 vs. 99±0% in controls, of ingested amount, p<0.05). EFA deficiency did not affect the histology or proliferative capacity of the small intestine as demonstrated by the histological and proliferative staining, and by the morphometrcal measurements of the small intestinal villi. Blood C6-glucose appearance and disappearance were similar in both groups, indicating unaffected monosaccharide absorption. In contrast, blood appearance of 13C-glucose, originating from 13C-lactose, was delayed in EFA-deficient mice. EFA deficiency profoundly reduced lactase activity (-58%, p<0.01) and mRNA expression (-55%, p<0.01) in mid small intestine. Both lactase activity and its mRNA expression strongly correlated with mucosal LA concentrations (r=0.89 and 0.79, resp., p< 0.01). Conclusions: EFA deficiency in mice inhibits the capacity to digest lactose, but does not affect small intestinal histology. These data underscore the observation that EFA deficiency functionally impairs the small intestine, possibly mediated by low LA levels in the enterocytes. This research was funded by the Dutch Digestive Foundation (MWO 04-38).

Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity

The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C12 and C14 analogs were without appreciable activity, whereas the C16 5-oxo-dienoic acid was a weak partial agonist. In contrast, the corresponding C18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead acid (5Z,8Z,11Z-eicosatrienoic acid), which accumulates in dietary essential fatty acid deficiency, by neutrophils. The main Mead acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B(3). We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty acid deficiency.

Effects of dietary lipids on the fatty acid composition and lipid metabolism of the green sea urchin Strongylocentrotus droebachiensis

The effects of different dietary lipids (hydrogenated coconut oil, corn oil, linseed oil, and mixtures of corn oil, linseed oil, menhaden oil, and/or soy lecithin) on the fatty acid composition of the sea urchin Strongylocentrotus droebachiensis were investigated. Dietary lipid compositions were reflected in the fatty acid profiles of sea urchin guts, gonads and shells. The shells had the highest level of 20:4n-6 and 20:5n-3, while the highest levels of monounsaturated fatty acids were seen in the guts. Tissue levels of 20:4n-6 and 20:5n-3 were influenced by the dietary levels of 18:2n-6 and 18:3n-3. The addition of soy lecithin to the diet (CLnML) enhanced the production and incorporation of 20:4n-6 in shell and gonad. Sea urchin also synthesized and incorporated 20 and 22 carbon non-methylene-interrupted dienoic fatty acids (NMIDs) in all tissue lipids. The NMID content varied among the different tissues and was influenced by the dietary lipid source. The hydrogenated coconut oil (HCO) diet resulted in the greatest NMID content, while the lowest levels were seen in sea urchins fed diets containing a mixture of corn oil, linseed oil, menhaden oil and lecithin (CLnML). The NMID content was lowest in gut and highest in the shell. Significant levels of mead acid (20:3n-9) were detected in the shells of sea urchins fed the EFA-deficient diet (HCO). The enzymatic capabilities of sea urchins to desaturate and elongate 18:2n-6 to 20:4n-6 and 18:3n-3 to 20:5n-3, as well as the capabilities to de novo synthesize NMID were hypothesized. Possible physiological roles and mechanisms for formation of NMID are discussed.

Influence of lipid class and fatty acid deficiency on survival, growth, and fatty acid composition in rainbow trout juveniles

Triplicate groups of rainbow trout (182 ± 51 mg) were fed four experimental casein–gelatin based diets containing different fatty acid levels for 8 weeks. Diet 1, containing only the oleic acid methyl ester (18:1 n − 9), was used as an essential fatty acids deficient diet. Diet 2, supplemented with olive and linseed oils was designed to provide moderate amount of linoleic (18:2 n − 6) and linolenic (18:3 n − 3) acids in the form of triglycerides. Diet 3 contained cod liver oil and provided highly unsaturated fatty acids (HUFA) as well as their precursors. Diet 4, supplemented with soy-refined lecithin, contained high levels of 18:2 n − 6 in the form of phospholipids. At the end of the experiment, the growth of fish fed the lecithin supplemented diet was significantly higher (17 fold increase) than that of the other groups (6–14 fold increase). Survival was significantly lower in fish fed the diet 1 in comparison to fish fed the other experimental diets (57.8% vs. 84.4–86.7%). Fish fed diets 1 and 4 contained significantly less total and neutral lipids in the whole body than fish fed diets 2 and 3. Whole body fatty acid profiles from both neutral and phospholipid fractions closely reflected dietary fatty acid composition. Fish fed linoleate containing phospholipids preferentially deposited this fatty acid in neutral lipids (33.0 ± 1.6%) in comparison to body phospholipids deposition (21.2 ± 1.0%). An increase of dietary linoleate also resulted in a significantly higher percentage of arachidonate (20:4 n − 6) in fish body phospholipids. In conclusion, selective accumulation of 18, 20, and 22 polyunsaturated fatty acids in body of juvenile rainbow trout is the function of fatty acid origin, e.g., lipid class, which has been very little studied in this species.

Influência da privação dos ácidos graxos essenciais na agregação de trombócitos em trutas arco-íris

Indicações sobre alterações na formação das células sanguíneas e em suas funções nos peixes têm sido relatadas em diversos trabalhos. Os ácidos graxos essenciais (EFA) certamente estão ligados a essas células devido ao fato de constituírem fonte de componentes importantes, como os eicosanoides, fatores de ativação de plaquetas nos mamíferos, bem como de fosfolipídios de membrana. Trombócitos oriundos de peixes alimentados com uma dieta comercial contendo quantidades adequadas de EFA mostraram uma grande capacidade de agregação quando induzidos por colágeno do tipo I (56%), contudo, essa capacidade encontrou-se reduzida quando os peixes foram alimentados com uma dieta deficiente em EFA (37%). Os resultados obtidos nesse estudo demonstraram que os ácidos graxos essenciais exercem influência nos trombócitos afetando sua capacidade de agregação.

Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice

Biliary phospholipids (PL) stimulate dietary fat absorption by facilitating intraluminal lipid solubilization and by providing surface components for chylomicron (CM) assembly. Impaired hepatic PL availability induces secretion of large very-low-density lipoproteins, but it is unclear whether CM size depends on biliary PL availability. Biliary PL secretion is absent in multidrug resistance protein 2-deficient (Mdr2(-/-)) mice, whereas it is strongly increased in essential fatty acid (EFA)-deficient mice. We investigated lymphatic CM size and composition in mice with absent (Mdr2(-/-)) or enhanced (EFA deficient) biliary PL secretion and in their respective controls under basal conditions and during enteral lipid administration. EFA deficiency was induced by feeding mice a high-fat, EFA-deficient diet for 8 wk. Lymph was collected by mesenteric lymph duct cannulation with or without intraduodenal lipid administration. Lymph was collected in 30-min fractions for up to 4 h, and lymphatic lipoprotein size was determined by dynamic light-scattering techniques. Lymph lipoprotein subfractions were isolated by ultracentrifugation, and lipid composition was measured. Lymphatic CMs were significantly larger in Mdr2(-/-) mice than in Mdr2(+/+) controls either without (+50%) or with (+25%) enteral lipid administration, and molar core-surface ratios were increased [triglyceride (TG)-to-PL ratio: 4.4 +/- 1.4 in Mdr2(-/-) mice vs. 2.7 +/- 0.8 in Mdr2(+/+) mice, P < 0.001]. In contrast, EFA-deficient mice secreted lipoproteins into lymph that were significantly smaller than in EFA-sufficient controls (173 +/- 32 vs. 236 +/- 47 nm), with correspondingly decreased core-surface ratios (TG-to-PL ratio: 3.0 +/- 1.0 in EFA-deficient mice vs. 6.0 +/- 1.9 in EFA-sufficient mice, P < 0.001). CM size increased during fat absorption in both EFA-deficient and EFA-sufficient mice, but the difference between the groups persisted. In conclusion, the present results strongly suggest that the availability of biliary PL is a major determinant of the size of intestinally produced lipoproteins both under basal conditions and during lipid absorption. Altered CM size may have physiological consequences for postprandial CM processing.

Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis

Delta6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction. Paradoxically, D6D is also induced by ligands of peroxisome proliferator-activated receptor alpha (PPARalpha). Here, we report a novel physiological role of PPARalpha in the induction of genes specific for HUFA synthesis by essential fatty acid-deficient diets. D6D mRNA induction by essential fatty acid-deficient diets in wild-type mice was diminished in PPARalpha-null mice. This impaired D6D induction in PPARalpha-null mice was not attributable to feedback suppression by tissue HUFAs because PPARalpha-null mice had lower HUFAs in liver phospholipids than did wild-type mice. Furthermore, PPARalpha-responsive genes were induced in wild-type mice under essential fatty acid deficiency, suggesting the generation of endogenous PPARalpha ligand(s). Contrary to genes for HUFA synthesis, the induction of other lipogenic genes under essential fatty acid deficiency was higher in PPARalpha-null mice than in wild-type mice even though mature SREBP-1c protein did not differ between the genotypes. The expression of PPARgamma was markedly increased in PPARalpha-null mice and might have contributed to the induction of genes for de novo lipogenesis. Our study suggests that PPARalpha, together with SREBP-1c, senses HUFA status and confers pathway-specific induction of HUFA synthesis by essential fatty acid-deficient diets.

MARKED CHANGES IN THE MRNA EXPRESSION OF PPARS IN THE LIVER OF MICE WITH PERINATAL ESSENTIAL FATTY ACID DEFICIENCY

Peroxisome proliferators-activated receptors (PPAR) are nuclear receptors which by transcription are regulating genes involved in lipid and glucose metabolism as well as in cell growth and inflammation. Perinatal changes in essential fatty acid (EFA) metabolism can program for long-term effects related to the metabolic syndrome in the rat. The aim of the present study was to investigate if similar changes would be induced in the mice and to study gene expression in order to clarify involved metabolic disturbances. Methods: Mice of C57BL/6 strain were given EFA deficient or control diet from day 15 of pregnancy and during lactation. The pups were killed at weaning (3 w) and different organs dissected and frozen in −70° until analysis. Lipids (HPLC and GLC) and PPAR mRNA (real-time PCR) were analysed in liver. Results: The pups of EFA deficient mothers were sign smaller and had lower liver weight, also related to bw than controls. Serum FA showed marked EFA deficiency, mean(SD) linoleic acid (LA) being 1.60(0.07) vs 29.9(2.9) mol% and EFA deficiency index being 3.7(0.5) vs 0.00(0.00) (p < 0.000001). Liver phospholipid (PL) pattern (mg/g liver weight) showed only differences between phosphatidylserine (PS), sphingomyelins (SMs) and phosphatidylglycerol but the FA pattern was markedly changed in most PL. LA was decreased in all PL (p < 0.00001) as was arachidonic acid (AA). The concentration of docosahexaenoic acid (DHA) was decreased in all PL but phosphatidylethanolamine (PE) and SMs and increased in diphosphoglycerol (DPG) (p < 0.0001). The AA/DHA ratio was significantly decreased compared to controls except in SMs, PS and PE. The mRNA expression in the liver of PPARdelta was decreased 0.8 (0.08) vs 1.67 (0.43) (p < 0.005) and PPARgamma increased 1.67 (0.21) vs 0.61 (0.23) (p < 0.0001) but PPARalpha was unchanged. Summary: Selective marked changes in FA composition of PL was associated with different expression of PPAR delta and PPAR gammabut relative preservation of PE and PPAR alpha. Conclusion: Long-term follow up after FA restitution will reveal if the PPAR changes are permanent and related to the long-term effects in metabolism previously found in rats.

Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Essential fatty acid (EFA) deficiency in mice decreases plasma triglyceride (TG) concentrations and increases hepatic TG content. We evaluated in vivo and in vitro whether decreased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) contributes to this consequence of EFA deficiency. EFA deficiency was induced in mice by feeding an EFA-deficient (EFAD) diet for 8 wk. Hepatic VLDL secretion was quantified in fasted EFAD and EFA-sufficient (EFAS) mice using the Triton WR-1339 method. In cultured hepatocytes from EFAD and EFAS mice, VLDL secretion into medium was measured by quantifying [(3)H]-labeled glycerol incorporation into TG and phospholipids. Hepatic expression of genes involved in VLDL synthesis and clearance was measured, as were plasma activities of lipolytic enzymes. TG secretion rates were quantitatively similar in EFAD and EFAS mice in vivo and in primary hepatocytes from EFAD and EFAS mice in vitro. However, EFA deficiency increased the size of secreted VLDL particles, as determined by calculation of particle diameter, particle sizing by light scattering, and evaluation of the TG-to-apoB ratio. EFA deficiency did not inhibit hepatic lipase and lipoprotein lipase activities in plasma, but increased hepatic mRNA levels of apoAV and apoCII, both involved in control of lipolytic degradation of TG-rich lipoproteins. EFA deficiency does not affect hepatic TG secretion rate in mice, but increases the size of secreted VLDL particles. Present data suggest that hypotriglyceridemia during EFA deficiency is related to enhanced clearance of altered VLDL particles.

Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats

Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls ( P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased ( P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased ( P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified.

Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice.

To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)-induced body fat loss or DNA fragmentation. Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA-supplemented mice and was not affected by fat source. Reductions in linoleic acid concentration made mice more sensitive to CLA-induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.

Treatment of EFA deficiency with dietary triglycerides or phospholipids in a murine model of extrahepatic cholestasis.

Essential fatty acid (EFA) deficiency during cholestasis is mainly due to malabsorption of dietary EFA (23). Theoretically, dietary phospholipids (PL) may have a higher bioavailability than dietary triglycerides (TG) during cholestasis. We developed murine models for EFA deficiency (EFAD) with and without extrahepatic cholestasis and compared the efficacy of oral supplementation of EFA as PL or as TG. EFAD was induced in mice by feeding a high-fat EFAD diet. After 3 wk on this diet, bile duct ligation was performed in a subgroup of mice to establish extrahepatic cholestasis. Cholestatic and noncholestatic EFAD mice continued on the EFAD diet (controls) or were supplemented for 3 wk with EFA-rich TG or EFA-rich PL. Fatty acid composition was determined in plasma, erythrocytes, liver, and brain. After 4 wk of EFAD diet, induction of EFAD was confirmed by a sixfold increased triene-to-tetraene ratio (T/T ratio) in erythrocytes of noncholestatic and cholestatic mice (P < 0.001). EFA-rich TG and EFA-rich PL were equally effective in preventing further increase of the erythrocyte T/T ratio, which was observed in cholestatic and noncholestatic nonsupplemented mice (12- and 16-fold the initial value, respectively). In cholestatic mice, EFA-rich PL was superior to EFA-rich TG in decreasing T/T ratios of liver TG and PL (each P < 0.05) and in increasing brain PL concentrations of the long-chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid and arachidonic acid (each P < 0.05). We conclude that oral EFA supplementation in the form of PL is more effective than in the form of TG in increasing LCPUFA concentrations in liver and brain of cholestatic EFAD mice.

Significant Increase in Survival of Captive‐bred Juvenile Banggai Cardinalfish Pterapogon kauderni with an Essential Fatty Acid‐Enriched Diet

Abstract Pterapogon kauderni is an endemic, direct developing, coral reef fish from Indonesia, which has become very popular in the aquarium community. During development of a captive breeding program, high frequency of shock syndrome events and associated mortality was observed in juveniles fed a diet of newly hatched Anemia. After about a week post‐release, juveniles became extremely sensitive to external stimuli, such as feeding and turning the lights on. A series of five tests (mean duration = 116 d) were conducted to investigate a possible dietary essential fatty acid deficiency. A significant increase in survival (P &lt; 0.001) and decrease in frequency of shock syndrome events (P &lt; 0.05) were observed in juveniles fed a highly unsaturated fatty acid‐enriched diet. Juveniles fed the un‐enriched diet suffered a mean of 1.4 events/ individual, whereas those fed the enriched diet had a significantly lower mean of 0.08 (P &lt; 0.001). Mean mortality (all tests) for juveniles fed the un‐enriched diet was 80.7%. whereas it was 5.3% for those fed the enriched diet. No individual fed the enriched diet died after suffering a shock event, whereas in four out of five tests several individuals (mean = 2.26) fed the un‐enriched diet died a few minutes after the event. No event was observed during the first week after juvenile release: the mean days at which the first event occurred (all tests) were 26.8 (un‐enriched) and 26 (enriched). and the mean week at which the highest frequency of shock events occurred was 4.7 (un‐enriched). The results of this study have particular significance for conservation because of the threatened status of P. kauderni.

Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3.

The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n-3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.

Patología de la placenta de rata inducida por la deficiencia de ácidos grasos

Lipids are important ceil components, both from the structural and the functional point of view. Besides they intervein in transportingfunctions, cell recognition and immunity. Essential Fatty Acids (EFA) are important for the functional and structural maintenance ofanimal organisms. In our laboratory, it was demonstrated that one group of pregnant rats fed on an EFA deficient diet, and other group of rats fed onthe same diet but with 5% of corn oil (rich in linoleic acid) showed alterations on the development of the metrial gland. In the present work, 57 female rats of a Wistar strain were fed since weaning with one of the followingdiets : EFAD :deficient in essential fatty acids, COD: EFAD + 5% corn oil (linoleic acid sufficient but (x- linoleic acid deficient); SAD: EFAD + 5% soy oil (both EFA sufficient) and CD: commercial diet. After 3 months theanimals were sacrificed on the 13 th. day ofgestation.Uteru's horns were dissected and the irnplantation sities were fixed on formo] and embebbed in parafine. The observations were carried out with RÍE coloured cross-sectionsand the corialantoidea placenta, the sities of implanctations and the sitios of reabsortions were studied. The metrial gland of DAGE andDAM rats presented structural modifications compared to DC rats. The most relevant findings were: indifferentiation of thegranulated metrial gland celis and an increase in the amount of connective tissue. 188 GLOCKER T. M.In DAS rats, on the contrary, the aspectof the metrial gland was similar to the observedin the DC group. In the DAGE and the DAMgroups Labyrinthum was enlarged withvascular septum group . Mean while DAS wassimilar to group DC (thin and vascular).Differences in the sities of implanctations andreabsortions were not detected. The presentresults suggest that a- linolenico acid isessential for the rat placenta to reach normaldevelopment.

Maternal dietary intake of essential fatty acids affects adipose tissue growth and leptin mRNA expression in suckling rat pups.

We have previously shown that maternal intake of essential fatty acids during late gestation and lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in white adipose tissue of pups during the suckling period. During late gestation and throughout lactation, rats were fed a control or an essential fatty acid-deficient (EFAD) diet. Milk of the EFAD dams contained more saturated and less polyunsaturated fatty acids compared with the control dams. Milk leptin levels were higher in the EFAD dams than in the control dams at 3 wk of lactation. The weight of inguinal white adipose tissue depots and the serum leptin levels of the EFAD pups were significantly lower than in the control pups during the whole suckling period. In addition, semiquantitative reverse transcriptase-PCR analysis of leptin mRNA levels in inguinal white adipose tissue showed a reduction in the EFAD pups compared with the control pups at 3 wk of age. We conclude that maternal dietary essential fatty acid intake affects serum leptin levels in pups by regulating both the amount of adipose tissue and the leptin mRNA expression.

Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and peripheral tissues in essential fatty acid deficiency.

Fatty acid status in humans is usually related to plasma or red blood cell fatty acid profiles. The aim of the study was to explore whether a maternal deficiency in dietary essential fatty acids would differentially affect lipid fractions in several tissues of the offspring, including brain. Female Wistar rats were fed an essential fatty acid-deficient diet during 3 months before mating. The fatty acid composition of different lipid fractions was examined in maternal milk, and in plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus of the offspring using thin layer and capillary column gas chromatography. Lipid fractions from most tissues of deprived offspring showed a common fatty acid profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not affected in brain, even though 22:5 omega6 was increased in phospholipids of cerebral cortex and hippocampus. The present results demonstrate different degrees of resistance to essential fatty acid deficiency in lipid fractions and tissues. This suggests a priority distribution of arachidonic acid to preferential areas and shows that blood phospholipid fatty acids do not exactly reflect brain phospholipid status.

Docosahexaenoic Acid Is Superior to Eicosapentaenoic Acid as the Essential Fatty Acid for Growth of Grouper, Epinephelus malabaricus

Juvenile grouper (Epinephelus malabaricus) were fed seven experimental diets, one control diet and one reference diet for 12 wk to determine the dietary requirement of grouper for docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Each of the seven diets contained 1 g/100 g DHA and EPA in various combinations and 9 g/100 g tristearin. The control diet contained 1 g/100 g trilinolenin and trilinolein (3:1, wt/wt), and no supplemental EPA or DHA. The reference diet contained only natural oils from a mixture of cod liver oil, linseed oil and safflower oil at a ratio of 2:1:1 (wt/wt/wt). Significant differences (P < 0.05) in growth were observed among the dietary treatments but not in survival rate or relative liver weight. Only the diet with the highest DHA/EPA ratio (3:1) promoted significantly greater growth than the control diet. Purified EPA and DHA did not perform better in promoting growth than did the impure EPA and DHA oils. Enhanced growth was observed when the dietary DHA/EPA ratio was greater than 1, indicating that DHA was superior to EPA in promoting fish growth. Neutral lipid (NL) was the predominant lipid fraction (>70%) in both liver and muscle. Tissue NL/polar lipid did not differ among groups except the reference diet group that had a higher ratio (P < 0.05). DHA and EPA levels in the grouper tissues, especially muscle, were highly reflective of dietary levels of DHA and EPA, indicating that direct incorporation was likely. In addition, the 20:1(n-9), concentration in NL fractions seems to be an appropriate indicator of dietary essential fatty acid deficiency in grouper.

Quality of eggs and spermatozoa of rainbow trout fed an n-3 essential fatty acid-deficient diet and its effects on the lipid and fatty acid components of eggs, semen and livers

: The effect of an n-3 essential fatty acid (EFA) -deficient diet on spawning and on the lipid and fatty acid contents of eggs, semen and livers of rainbow trout Oncorhynchus mykiss was investigated. Fish were split into two groups and fed either of two diets for a period of 4 months prior to the start of the spawning season. The control group was fed a commercial diet, containing n-3 EFA, whereas the experimental group was fed an n-3 EFA-deficient diet. Fish were 3 years old at the time of spawning. Eggs and semen were stripped off five females and five males from each diet group and cross-fertilized. Two of the five males fed the deficient diet showed a lower sperm motility, resulting in slightly lower mean hatching rates when crossed with eggs of either group. Higher lipid contents in the EFA-deficient diet were reflected in the egg and semen lipid contents, whereas the lipid contents of male livers of both diet groups were higher than those of female livers. In livers and eggs, the main polar lipid was phosphatidylcholine accompanied by phosphatidylethanolamine in sperm polar lipids. The non-polar lipids of eggs were mainly triacylglycerols but in livers and semen, free fatty acids and free sterols were more abundant. Essential fatty acids, namely n-3 highly unsaturated fatty acids and linolenic acid, were generally lower in eggs, semen and livers sampled from the EFA-deficient diet group. These results indicate that the fertilization, eyed and hatching rates obtained from crossings with males fed the EFA-deficient diet were slightly lower because of the dietary effect on sperm motility. Moreover, lipids of eggs, semen and livers of male and female rainbow trout were influenced greatly by their dietary availability.