EFA-deficient Diet Research Articles

Effect of Dietary Fish Oil on Plasma Thromboxane B2 and 6-Keto-prostaglandin F1α Levels in Septic Rats

Increased mortality from sepsis is associated with high levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha). Linoleic acid, an n-6 essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish oil is rich in n-3 essential fatty acid, the precursor of less active moieties. Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks. The animals then underwent a sham operation or cecal ligation and puncture to induce sepsis. Six hours later, blood was obtained for analysis. The chow and linoleic acid diets produced significant (twofold to fivefold) increases in levels of both TXB2 and PGF1 alpha after sepsis. The essential fatty acid-deficient diet and fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during sepsis. Dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis.

Differential effects of dietary fatty acids on fatty acid composition of phosphotidylinositol in calf tissues

Fatty acid compositions of phosphatidylinositol (PI) in calf liver, heart, muscle, and brain were measured, as affected by dietary treatments. High Cu intake (1000 ppm) decreased 18:0 in liver PI and increased 18:1 n-9 and 18:2 n-6 in liver and heart; the reversed changes were observed in skeletal muscle PI. Additional high Zn intake (1000 ppm) inhibited the high Cu effects. Feeding an essential fatty acid (EFA) deficient diet markedly decreased 18:2 n-6, 20:3 n-6, and 20:4 n-6, and increased 18:1 and 20:3 n-9 in liver and heart PI. A high intake of 18:2 n-6 (corn oil) increased 18:2 n-6, but decreased 20:4 n-6, in liver, heart and muscle PI. Dietary fish oil concentrate (high in eicosapentaenoic acid) increased 20:5 n-3 in liver, heart, and muscle PI. Fatty acid composition of brain PI was resistant to different dietary regimens. Dietary imposed changes in fatty acid composition of PI in liver, heart, and muscle may have important implications in transmembrane signalling, eicosanoid production and other functions attributed to PI in tissues.

Multicentric focal acinar cell hyperplasia and hepatocyte-like cell metaplasia are induced by nitrosomethylurea in rat pancreas

The present report is a study of the effect of the carcinogen nitrosomethylurea (NMU) on pancreas of rats receiving during lifetime a lipid-poor diet, that is essential fatty acid deficient or control diets. Rats fed a commercial stock chow were mated. At day 10 of pregnancy, dams were divided into three groups, that were respectively supplied with the commercial chow, the essential fatty acid deficient or the sufficient diet. Each litter was separated at random in two groups that received at day one of life one intraperitoneal injection of NMU (50 mg/kg b.w.) or saline. After weaning, they were maintained for life with the diet that was supplied to their mothers. The pancreas of NMU-treated rats presented diffuse proliferative changes, focal acinar cell hyperplasias (FACH), and focal hepatocyte-like metaplasia (FHLCM). FACH were expansive presumably preneoplastic growths, showing abnormal differentiation. The number of NMU-treated rats bearing FACH and FHLCM did not significantly differ in the three nutritional conditions.

Effect of dietary essential fatty acid deficiency on Ca 2+-atpase activity in microsomal fraction of rat submandibular gland

1. 1. The effect of dietary essential fatty acid (EFA) deficiency on Ca 2+-ATPase activity of rat submandibular gland microsomal fraction was studied. 2. 2. The specific activity of Ca 2+-ATPase per milligram of microsomal protein was depressed about 35% in rats fed the EFA-deficient diet as compared with that in those fed the control diet. 3. 3. Lineweaver-Burk plots for Ca 2+-ATPase activity showed no significant differences in K m values for Ca 2+ and ATP, but the V max ., was decreased in the EFA-deficient rats. 4. 4. The above results suggest that depression of the Ca 2+-ATPase activity in rats fed the EFA-deficient diet is probably due to the decrease in the V max of the enzyme.

The effect of essential fatty acid deficiency on eicosanoid production in the inflamed rat colonic mucosa

Eicosanoids are potent mediators of inflammation and are synthesized in increased quantity in active ulcerative colitis. To elucidate the role of prostaglandin E 2, thromboxane A 2, prostaglandin I 2, and leukotriene B 2 in acute chemical colitis induced by 4% acetic acid, we utilized an animal model which has a deficiency of arachidonic acid, the precursor of eicosanoids due to an essential fatty acid deficient diet. Fortyeight hours after colitis was induced, mucosal synthesis of the cyclooxygenase products, prostaglandin E 2, thromboxane A 2, and prostaglandin I 2, was significantly decrease in essential fatty acid deficient rats compared to normal controls. However, the 5-lipoxygenase product, leukotriene B 4, was not different between groups. The decrease in cyclooxygenase products did not correlate with any change in the severity of colonic inflammation as assessed by gross morphology, histology, or myleoperoxidase activity. Thus inhibition of formation of the cyclooxygenase products of arachidonate metabolism does not appear to improve the degree of inflammation under the experimental conditions employed in this study.

The effect of essential fatty acid deficiency on the adrenergic activation of glycogenolysis in rat hepatocytes

The fatty acid composition of total lipids and the adrenoceptor-mediated activation of glycogenolysis were studied in isolated hepatocytes from rats maintained on a control diet or on an essential fatty acid (EFA)-free diet. In cells from rats on the EFA-free diet there was a marked reduction in linoleic and arachidonic acid (AA) contents and an increase in eicosatrienoic, oleic, and palmitoleic acid contents compared to controls. In freshly isolated cells from both groups, phosphorylase a activity was increased by phenylephrine or epinephrine but not by isoproterenol, and the effect of epinephrine was inhibited by phenoxybenzamine but not by propranolol. When control cells were preincubated in a serum-free buffer for 4 h before testing, the effect of phenylephrine on phosphorylase a activity was reduced, isoproterenol became a potent agonist and the effect of epinephrine was partially inhibited either by phenoxybenzamine or by propranolol. The emerging β-adrenergic response in 4-h cells was associated with a marked potentiation of isoproterenol-induced cAMP accumulation. A similar 4-h preincubation of EFA-deficient cells resulted in a reduced response to phenylephrine while isoproterenol remained ineffective for increasing either phosphorylase a activity or cAMP production. The response of these 4-h cells to isoproterenol could be restored by in vivo replacement of the EFA-deficient diet with control diet for the last 4 weeks prior to the experiment, but not by the in vitro exposure of the EFA-deficient cells to 10 μ m AA throughout the 4-h incubation period. Extending previous observations (Refs. (6–8)), the present results suggest that the time-dependent emergence of β-adrenergic glycogenolysis, but not the parallel reduction of the α-adrenergic response, is mediated by AA or its metabolite(s), which probably act by facilitating the G-protein-dependent coupling of β-receptors.

Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin.

The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function.

Influence of essential fatty acid deficient diet in acetic acid colitis in the rat

Influence of essential fatty acid deficient diet in acetic acid colitis in the rat

Influence of essential fatty acid deficient diet on some manifestations of endotoxin shock in rats

Influence of essential fatty acid deficient diet on some manifestations of endotoxin shock in rats

Essential Fatty Acid Nutrition of the American Alligator (Alligator mississippiensis)

The essential fatty acid (EFA) nutrition of young American alligators (Alligator mississippiensis) was examined by feeding a variety of fats/oils with potential EFA activity. Over a 12-wk period, alligators fed diets containing 2.5 or 5.0% chicken liver oil grew longer and heavier and converted feed to body mass more efficiently than alligators fed other fat/oil combinations that lacked or contained only trace amounts of arachidonic acid [20:4(n-6)]. Alligators fed an EFA-deficient diet (containing only coconut fat as the dietary fat) were the slowest-growing animals and converted feed to body mass least efficiently. However, over a 41-wk feeding period, alligators fed this diet showed no obvious external signs of deficiency other than being reduced in size and unthrifty. Fatty acid composition of heart, liver, muscle, skin and adipose tissue lipids was influenced markedly by dietary fat composition. Tissues varied significantly in response to dietary fat composition. Heart lipids contained the lowest levels of short- and medium-chain fatty acids and the highest levels of arachidonic acid. Arachidonic acid levels were less influenced by diet than were levels of other 20- and 22-carbon polyunsaturated fatty acids. Radiotracer studies indicated that linoleic acid was converted to arachidonic acid in the liver. Nevertheless, tissue arachidonic acid levels also appeared to be maintained by concentration from dietary sources and selective conservation. It appears that a dietary source of arachidonic acid may be required for a maximum rate of growth.

Diet‐Induced Alterations of Lipids During Cell Differentiation in the Small Intestine of Growing Rats

SummaryThe lipid components of columnar cells harvested from rat small intestine were analyzed at each step of cell maturation. The effect of dietary lipids on the evolution of lipids in differentiating cells was studied using two diets representative either of a control or of an essential polyunsaturated fatty acid deficient lipid supply. Two groups of weanling rats were fed a semisynthetic diet composed of corn oil (control diet) or hydrogenated coconut oil (deficient diet) for 11 weeks. Intestinal cells were extracted according to their position along the villus column. Linoleic and arachidonic acids constitutive of cell phospholipids increased as cells migrated from the lower to the mid‐part of the crypt‐villus axis only with the control diet. This gradient disappeared after a 3‐week feeding period with hydrogenated coconut oil diet so that columnar cells of essential fatty acid deficient rats exhibited the same overall fatty acid composition all along the crypt‐villus axis. Essential fatty acid deficiency resulted in an increase of both the triene to tetraene and arachidonic acid to linoleic acid weight ratios regardless of the maturational step of cells. As compared to the control diet, the essential fatty acid deficient diet induced a decrease of both the cholesterol and free fatty acid to phos‐pholipid molar ratios only in lower villus cells. We conclude that (a) progressive compositional modifications of lipids occur while ascending the crypt‐villus axis and (b) essential fatty acid deficiency induces substantial alterations of the lipid evolution normally linked to cell differentiation.

Diet-Induced Alterations of Lipids During Cell Differentiation in the Small Intestine of Growing Rats

The lipid components of columnar cells harvested from rat small intestine were analyzed at each step of cell maturation. The effect of dietary lipids on the evolution of lipids in differentiating cells was studied using two diets representative either of a control or of an essential polyunsaturated fatty acid deficient lipid supply. Two groups of weanling rats were fed a semisynthetic diet composed of corn oil (control diet) or hydrogenated coconut oil (deficient diet) for 11 weeks. Intestinal cells were extracted according to their position along the villus column. Linoleic and arachidonic acids constitutive of cell phospholipids increased as cells migrated from the lower to the mid-part of the crypt-villus axis only with the control diet. This gradient disappeared after a 3-week feeding period with hydrogenated coconut oil diet so that columnar cells of essential fatty acid deficient rats exhibited the same overall fatty acid composition all along the crypt-villus axis. Essential fatty acid deficiency resulted in an increase of both the triene to tetraene and arachidonic acid to linoleic acid weight ratios regardless of the maturational step of cells. As compared to the control diet, the essential fatty acid deficient diet induced a decrease of both the cholesterol and free fatty acid to phospholipid molar ratios only in lower villus cells. We conclude that (a) progressive compositional modifications of lipids occur while ascending the crypt-villus axis and (b) essential fatty acid deficiency induces substantial alterations of the lipid evolution normally linked to cell differentiation.

Variations in energization parameters and proton conductance induced by cold adaptation and essential fatty acid deficiency in mitochondria of brown adipose tissue in the rat

Male weanling Long-Evans rats were fed on a low-fat semipurified diet (control diet, 2% sunflower oil; essential fatty acid (EFA) deficient diet, 2% hydrogenated coconut oil) for 9 weeks. In order to modulate need for non-shivering thermogenesis, groups of rats on each diet were exposed at 28°C (thermoneutrality) and at 5°C (cold acclimation) for the last 5 weeks. In brown adipose tissue (BAT) mitochondria, several parameters of mitochondrial energization, protonmotive force ( Δp) and its components ΔpH and membrane potential, Δψ, were investigated. Simultaneous measurement of oxygen consumption and Δψ (the main component of Δp) was performed by varying α-glycerophosphate concentration and the force / flux relationship of the mitochondria was established by comparison of proton conductance, C m H + , over the whole range of protonmotive force, Δp. In the absence of GDP, at 28°C, EFA deficiency induced a marked increase in C m H + . Cold acclimation led to comparable enhanced C m H + in control and EFA-deficient mitochondria. In the presence of GDP which binds and inhibits the BAT 32 kDa uncoupling protein, C m H + was the same in 28°C and 5°C control mitochondria, but EFA deficiency led to an enhanced GDP independent C m H + at 28°C and to a lesser extent at 5°C. These results are discussed with reference to substantial changes in mitochondrial lipid composition induced by the deficiency.

Non-shivering thermogenesis and brown adipose tissue activity in essential fatty acid deficient rats

The effects of essential fatty acid (EFA) deficiency on energetic metabolism and interscapular brown adipose tissue (BAT) activity were examined in the cold acclimated rat. Weanling male Long-Evans rats were fed on a low fat semipurified diet (control diet, 2% sunflower oil; EFA deficient diet, 2% hydrogenated coconut oil) for 9 weeks. They were exposed at 5 degrees C for the last 5 weeks. In EFA deficient rats, compared to controls, growth retardation reached 22% at sacrifice. Caloric intake being the same in the two groups, it follows that food efficiency was decreased by 40%. Resting metabolism in relation to body surface area was 25% increased. Calorigenic effect of norepinephrine (NE) in vivo (test of non-shivering thermogenesis) underwent a marked decrease of 34%. BAT weight was 21% decreased but total and mitochondrial protein content showed no variation. A 26% increase in purine nucleotide binding per BAT (taken as an index of thermogenic activity) was observed, suggesting that the enhancement in resting metabolism observed was mainly due to increased BAT thermogenesis. However, BAT mitochondria respiratory studies which are more direct functional tests showed a marked impairment of maximal O2 consumption of about 30% with palmitoyl-carnitine or acetyl-carnitine (both in presence of malate) or with alpha-glycerophosphate as substrate. It is likely that this impaired maximal BAT oxidative capacity may explain the impaired NE calorigenic effect in vivo. A possible increase in mitochondrial basal permeability is also discussed.

Increased liver lipase activity in rats with essential fatty acid deficiency.

Liver lipase activity was measured in EFA-deficient rats (long-term) and in control rats and rats fed an EFA-deficient diet for two weeks (short-term). Liver lipase activity was significantly enhanced by EFA deficiency, both in long-term and short-term experiments. The enhanced liver lipase activity could be normalized by feeding these rats normal laboratory chow for 14 days. Since during EFA deficiency prostaglandin synthesis is impaired, the possible involvement of prostaglandins in the observed changes in liver lipase activity during EFA deficiency was studied. Administration of the prostaglandin synthesis inhibitor indomethacin (5 mg/kg body weight, i.p.) to normally fed rats for two days led to an increase of liver lipase activity. Prostaglandin E2 was found to inhibit the secretion of liver lipase activity by freshly isolated parenchymal liver cells in vitro. These results indicate that the increase in liver lipase activity during EFA deficiency may be due to an impairment of the prostaglandin synthesis.

Essential fatty acid deficiency during acute puromycin nephrosis ameliorates late renal injury.

Puromycin aminonucleoside (PA) nephrosis is associated with a significant increase in the glomerular macrophage number during peak proteinuria. The significance of this observation remains uncertain. An essential fatty acid-deficient (EFAD) diet depletes normal rat glomeruli of resident macrophages and alters glomerular eicosanoid metabolism. In this study, we found that an EFAD diet, administered only for the duration of the acute nephrotic phase, significantly ameliorated the recurrent albuminuria, renal dysfunction, and morphological injury characteristic of the late, recurrent phase of chronic aminonucleoside nephrosis. Glomerular macrophage number, isolated glomerular thromboxane B2 production, and circulating leukocyte and monocyte counts were significantly reduced in nephrotic rats on the EFAD diet 2 wk after PA injection, which temporally corresponds to peak albuminuria. The exact mechanism(s) by which the EFAD diet conferred protection in the late phase of chronic aminonucleoside nephrosis and lowered glomerular macrophage number during the acute nephrotic phase remain to be elucidated.

Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet

Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.

Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat

Renal distribition of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/ minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, and 18% reduction (p < 0.25). Second study: Male Sprague-Dawley rats were made prostaglanding deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin defecient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p < .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.

Essential fatty acid deficiency inhibits early but not late leukocyte infiltration in rabbit myocardial infarcts

Essential fatty acid (EFA) deficiency, induced by elimination of the dietary (n-6) fatty acids, has been shown to limit inflammatory cel influx and consequent enhanced eicosanoid production in experimental glomerulonephritis and hydronephresis. To determined whether EFA-deficiency exerts anti-inflammatory efects following left ventricular myocardial infarction (LVMI), male weanling rabbits were fed EFA-deficient diet for 3 months prior to 60 minutes of distal left circumflex coronary artery occlusion followed by reperfusion. One and 4 days later, corresponding to infiltration of cardiac tissue with polymorphonuclear (PMN) and mononuclear leukocytes respectively, infarcted hearts were buffer perfused and stimulated to produced eicosanoids with f-met-leu-phe or bradykinin. One day following LVMI, the hearts of EFA-deficient rabbits demonstrted a marked suppression of PMN infiltration and eicosanoid production relative to controls. Four days following myocardial infarction, no differences were obseved in mononuclear cell invasion, collagen deposition, or eicosanoid production between EFA-deficient and normal hearts. Our data show that EFA-deficiency inhibits PMN influx and consequent enhanced eicosanoid production without affecting the later appearance of mononuclear cells, collage deposition, or eicosanoid production. Recent studies have shown that suppression of PMN invasion limits the extent of tissue damage following LVMI. Selective inhibition of PMN infiltraton is possible and may be useful in the management of acute myocardial infarction.

Increased plasma triglyceride secretion in EFA-deficient rats fed diets with or without saturated fat.

Metabolic responses to essential fatty acid-deficiency in rats include an increased rate of triglyceride secretion into the plasma, a large reduction in the HDL1 plasma lipoprotein concentration, and increased concentrations of liver triacylglycerols and cholesteryl esters. Because of differences in the types of EFA-deficient diets used, it is not clear whether these responses were solely due to the absence of EFA from the diet or whether saturated fat, or differences in acyl group chain length in this fat, might be responsible. Therefore, we fed rats diets differing only in amounts and kinds of fat, and measured triacylglycerol secretion rates and liver concentrations of triacylglycerols and cholesteryl esters, for comparison with our earlier measurements of plasma high density lipoprotein subpopulations in rats fed exactly the same diets. The purified diets contained either no fat, 5% by weight hydrogenated coconut oil, 5% hydrogenated cottonseed oil, or each of these three diets supplemented with 1% safflower oil, or 5% corn oil. We also fed some rats a nonpurified stock diet for comparison with literature reports. The present results indicate that the metabolic responses to essential fatty acid deficiency described above are definitely due to essential fatty acid-deficiency and not to the presence or chain length of acyl groups in saturated fat in the diet.