Essentiality of omega 3 fatty acids for brain structure and function.
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Animals↗
Biomedical subjects
G Pascal
Publications and source records attributed to G Pascal.
Retinyl ester hydrolase and vitamin A status in rats treated with 3,3',4, 4'-tetrachlorobiphenyl.
Previous studies have shown that rats exposed to 3,3',4,4'-tetrachlorobiphenyl (TCB) exhibit decreased liver vitamin A stores. The activity of retinyl ester hydrolase (REH), the enzyme responsible for the hydrolysis of the storage form of vitamin A (retinyl esters) into free retinol, may therefore be altered by TCB. This study was carried out to investigate the effect of TCB on vitamin A distribution and on REH activity in the rat. REH activity was measured in liver homogenates and microsomes (650 micrograms protein), in Tris-maleate buffer 0.1 M at pH 7.2 in the presence of 150 mM CHAPS and 1.5 mM retinyl palmitate dispersed in Triton X-100 0.2%. Using these conditions, the kinetic parameters of the enzyme were determined and the inter-animal variation coefficient (10%) allowed statistical comparisons between experimental groups. Male Wistar rats of sufficient or deficient vitamin A status were treated IP with 340 mumol of TCB/kg. Vitamin A levels were significantly depressed in liver. REH activity was decreased about 20%, and serum retinol was decreased about 50%, independent of the initial vitamin A status of the animals. Vitamin A levels in lungs and testes were also decreased, suggesting that TCB could interfere with vitamin A delivery to target organs. The negative effect of TCB on REH activity in vivo was also observed when TCB was added in vitro to the incubation medium at concentrations near to those expected after in vivo treatment. TCB is a non-competitive inhibitor of retinyl palmitate hydrolase.
Animals↗
Tissue phospholipid fatty acid composition in genetically lean (Fa/-) or obese (fa/fa) Zucker female rats on the same diet.
The fatty acid composition of serum total lipids, of phospholipids of various organs (liver, heart, kidney), and of nervous structures (brain, retina, sciatic nerve, myelin, synaptosomes) have been compared in lean (Fa/-) and genetically obese (fa/fa) Zucker female rats. Both received a standard commercial diet including 37% of 18:2n-6 and 5% of n-3 polyunsaturated fatty acids (PUFA), 1.7% of which were in the form of 20:5n-3 and 22:6n-3. In comparison with lean rats, the results for the obese rats pointed out (i) no difference in the fatty acid composition of nervous structures; (ii) a decrease of 18:2n-6 (from -8% to -35%) and of 20:4n-6 (from -9% to -49%) in serum, liver and in kidney; this was compensated for by an increase in 20:3n-6 (from +30% to +320%) and in total n-3 PUFA (from +68% to +76%); (iii) a decrease of 20:4n-6 (-18%) and of 22:6n-3 (-24%) in heart compensated for by an increase in 18:2n-6 (+39%) and in 20:3n-6 (+233%); and (iv) constant levels of total PUFA (n-6 and n-3) in the various fractions studied, except in serum where this level decreased (-23%). Finally, except for the nervous structures, tissue phospholipids of obese rats included a lower proportion of 20:4n-6 and a higher proportion of 20:3n-6. This resulted in a significant reduction in the 20:4n-6/20:3n-6 ratio; by contrast, the 20:3n-6/18:2n-6 ratio increased. The results suggest that in Zucker rats, the obese character (fa/fa) affects the desaturation-elongation process of 18:2n-6 to 20:4n-6 by specifically decreasing delta 5-desaturase activity.
Animals↗
Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid.
Starting three weeks before mating, 12 groups of female rats were fed different amounts of linoleic acid (18:2n-6). Their male pups were killed when 21-days-old. Varying the dietary 18:2n-6 content between 150 and 6200 mg/100 g food intake had the following results. Linoleic acid levels remained very low in brain, myelin, synaptosomes, and retina. In contrast, 18:2n-6 levels increased in sciatic nerve. In heart, linoleic acid levels were high, but were not related to dietary linoleic acid intake. Levels of 18:2n-6 were significantly increased in liver, lung, kidney, and testicle and were even higher in muscle and adipose tissue. On the other hand, in heart a constant amount of 18:2n-6 was found at a low level of dietary 18:2n-6. Constant levels of arachidonic acid (20:4n-6) were reached at 150 mg/100 g diet in all nerve structures, and at 300 mg/100 g diet in testicle and muscle, at 800 mg/100 g diet in kidney, and at 1200 mg/100 g diet in liver, lung, and heart. Constant adrenic acid (22:4n-6) levels were obtained at 150, 900, and 1200 mg/100 g diet in myelin, sciatic nerve, and brain, respectively. Minimal levels were difficult to determine. In all fractions examined accumulation of docosapentaenoic acid (22:5n-6) was the most direct and specific consequence of increasing amounts of dietary 18:2n-6. Tissue eicosapentaenoic acid (20:5n-3) and 22:5n-3 levels were relatively independent of dietary 18:2n-6 intake, except in lung, liver, and kidney. In several organs (muscle, lung, kidney, liver, heart) as well as in myelin, very low levels of dietary linoleic acid led to an increase in 20:5n-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Effects of two prototypic polychlorinated biphenyls (PCBs) on lipid composition of rat liver and serum.
Mature male Sprague-Dawley rats received a single IP injection of either 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), 3,3',4,4'-tetrachlorobiphenyl (TCB) (300 microm/kg) in corn oil (10 ml/kg) or the corn oil vehicle alone, and were killed four days later after having been fasted overnight. The vehicle control group consisted of rats which were allowed free access to feed as well as pair-fed animals. Lipid analyses were conducted on liver, hepatic microsomes and serum. TCB- (but no HCB-) treatment resulted in a statistically significant increase in total liver lipids and triglycerides. Liver phospholipids remained unchanged. Both PCBs increased the cholesterol and phospholipids content of the liver microsomal fraction. Serum lipids measured were not statistically different from control values. While HCB had little effect on the fatty acid composition of liver lipids, TCB caused an increase in C 18:1 (n-9) and a decrease in C 20:4 (n-6). Both PCBs increased C 18:0 in the hepatic microsomal fraction, but TCB also decreased C 16:0. Neither PCB altered the fatty acid composition of serum total lipids. These data are consistent with the concept that specific alterations in lipid metabolism are dependent on the structure of the PCB.
Journal Article↗
Effect of vitamin A deficiency on the in vitro transfer of mannose and N-acetylglucosamine in rat liver nuclei.
Liver nuclei, prepared from normal and vitamin A-deficient rats, were incubated in the presence of GDP-(14C)mannose or UDP-N-acetyl(14C)glucosamine and the labelled glycoproteins analysed by SDS PAGE. Fluorographic analysis has shown that (14C) mannose labelling is enhanced by vitamin A deficiency whereas N-acetyl(14C)glucosamine transfer remains approximately at the same level regardless of the vitamin A status; we did not notice any modification when the proteins were monitored by Coomassie blue or by silver nitrate.
Acetylglucosamine↗
Nutritional fatty acids control. Composition and function of cerebral membranes.
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Animals↗
Control of brain fatty acids.
Saturated and monounsaturated fatty acids are mainly synthetized in the brain, but some of them could originate from the diet; in contrast polyunsaturated fatty acids are derived from dietary linoleic and linolenic acid. Saturated fatty acid biosynthesis occurs via three main pathways in mammalian cells. One is de novo synthesis of fatty acids from acetyl-CoA via malonyl-CoA; this system has been isolated in soluble form (the soluble system) from various animal tissues including brain. The second and third pathways involve elongation: in the mitochondrial system, acetyl CoA is the principal substrate in extracts from all organs, even brain; in the microsomal system, however, malonyl-CoA acts as donor of the 2 carbon fragments. In vivo studies in brain have shown that very long chain fatty acids are synthesized by elongation rather than by a than by a de novo mechanism. Feeding animals with oils that have a low n-3 acid content (linolenic series) results in all brain cells and organelles reduced amounts of 22:6 n-3 which is compensated for by an increase in 22:5 n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles and microvessels, in contrast with other organs. Essential fatty acids for the brain could be those with very long chains as shown with cell culture. They are probably synthesized in the liver from linolenic acid. They can also be supplied directly by food. During the period of cerebral development there is a linear relation between the n-3 acid content of the brain and that of food until linolenic acid represents approx. 200 mg per 100 g of food (for 1200 mg linoleic acid). A decrease in acids of the linolenic series in the membranes results in a 40% reduction of Na-K-ATPase in nerve terminals and a 20% reduction in 5'-nucleotidase in whole brain homogenate. A diet low in linolenic acid leads to anomalies in the electroretinogram which disappear partially with age, it seriously affects learning tasks. The presence of linolenic acid in the diet confers a greater resistance to certain neurotoxic agents.
Animals↗
[In vitro use of a model for studying the effects of tumor promoters in food].
Two antioxidants, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), which are widely used as food additives, have been proved in vivo to act as tumor promoters in rodent species. In order to study their mechanisms of action, BHT, BHA and phenobarbital (PB) were tested in vitro on liver epithelial cells isolated from 2-acetylaminofluorene-initiated rats. Interactions of BHT 3 x 10(-6) to 3 x 10(-5) M, BHA 10(-5) to 10(-4) M and of PB 10(-4) to 10(-3) M with cell growth on plastic dishes or in agarose, and with the expression of different proteins (gamma-glutamyltranspeptidase, cytoskeletal proteins, fibronectin) were followed.
Animals↗
Influence of vitamin A status and DDT on vitamin A-dependent protein mannosylation in rat liver.
Male Wistar rats of different vitamin A status (total depletion to moderate deficiency) were administered DDT (5 mg/kg/day) or vehicule (corn oil) i.p. daily for 14 days. Vitamin A-dependent protein mannosylation was measured either by in vivo incorporation of [3H]mannose into liver glycoprotein or by in vitro assay of incorporation of [14C]mannose into mannosylretinyl phosphate. Vitamin A deficiency resulted in a significantly impaired in vivo incorporation of mannose in liver glycoprotein but had no effect on the in vitro transport of mannose via retinyl phosphate. Although DDT induced an increase synthesis of liver proteins in smooth endoplasmic reticulum and caused a diminution of the hepatic vitamin A content, it did not affect vitamin A-dependent protein mannosylation.
Animals↗
Brain cell and tissue recovery in rats made deficient in n-3 fatty acids by alteration of dietary fat.
Rats were fed a purified diet containing either 1.5% sunflower oil [940 mg linoleic acid [18:2(n-6)]/100 g diet; 6 mg alpha-linolenic acid [18:3(n-3)]/300 g diet] or 1.9% soybean oil [940 mg 18:2(n-6)/100 g diet; 130 mg 18:3(n-3)/100 g diet]. In all cases and tissues examined 22:6(n-3) was lower and 22:5(n-6) was higher in rats fed sunflower oil than in rats fed soybean oil. Levels of 22:4(n-6) and 20:4(n-6) were largely unaffected. Expressed as a percentage of that in soybean oil-fed rats, 22:6(n-3) in sunflower oil-fed rats was as follows: neurons, 49; astrocytes, 47; oligodendrocytes, 10; lung, 27; testes, 32; retina, 36; liver, 35 and kidneys, 45. Ten wk after the change in diet of 60-d-old rats from one containing sunflower oil to one containing soybean oil, the fatty acid composition of the brain cells had not reached control values, e.g., that obtained in animals continuously fed soybean oil; 22:6(n-3) was 77, 65 and 80% of control levels for astrocytes, oligodendrocytes and neurons, respectively. In contrast, the recovery measured by the decay of 22:5(n-6) was complete within 10 wk. For 22:6(n-3), it took approximately 2 wk for liver and kidney to recover to the control value, 3 wk for lung, 6 wk for retina and 10 wk for testes. The decrease of 22:5(n-6) was rapid: the control values were reached within 2 wk for kidney, liver and lung and within 6 wk for retina.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats.
Feeding rats diets containing oils that have a low alpha-linolenic acid [18:3(n-3)] content, such as sunflower oil, results in reduced amounts of docosahexaenoic acid [22:6(n-3)] in all brain cells and organelles compared to rats fed a diet containing soybean oil or rapeseed oil. During the period of cerebral development there is a linear relationship between the n-3 fatty acid content of the brain and that of food until alpha-linolenic acid represents approximately 200 mg/100 g food [0.4% of the total dietary energy for 18:3(n-3)]. Beyond that point brain levels reach a plateau. Similar values are also found for other organs. The level of 22:6(n-3) in membranes is little affected by the dietary quantity of linoleic acid [18:2(n-6)] if 18:3(n-3) represents approximately 0.4% of energy. In membranes from rats fed diets containing sunflower oil, Na+, K(+)-ATPase activity in nerve terminals was 60%, 5'-nucleotidase in whole brain homogenate was 80%, and 2',3'-cyclic nucleotide 3'-phosphodiesterase was 88% of that in membranes from rats fed diets containing soybean oil. A diet low in alpha-linolenic acid leads to anomalies in the electroretinogram, which partially disappear with age. It has little effect on motor activity, but it seriously affects learning tasks as measured with the shuttle box test. Rats fed a diet low in alpha-linolenic acid showed an earlier mortality in response to an intraperitoneal injection of a neurotoxin, triethyltin, than did rats fed a normal soybean oil diet.
Animal Feed↗
Effects of dietary alpha-linolenic acid deficiency during pregnancy and lactation on lipid fatty acid composition of liver and serum in the rat.
The effects of a dietary alpha-linolenic acid (18:3 n-3) deficiency on lipid fatty acid composition of the liver and serum of lactating rats have been studied during three gestations and over three generations. These females were compared to corresponding females which remained sterile. Two lots of female rats received, respectively, a diet containing lipids either in the form of 1.50 g of sunflower oil per 100 g of diet (deficient diet) or as 1.87 g of soya oil per 100 g of diet (control diet). Both diet contained the same amount of linoleic acid (18:2 n-6), i.e. 940 mg/100 g of diet, but the sunflower diet supplied 43 times less 18:3 n-3 than the soja diet, or 3 mg vs 130 mg/100 g of diet. Results show that successive gestations appeared to be more efficient means of depleting material n-3 PUFA stores than successive generations. The 18:3 n-3 deficient diet caused a considerable decrease in the level of n-3 polyunsaturated fatty acids (n-3 PUFA) in liver and serum lipids, and particularly of 22:6 n-3. This decline was compensated by an increase in the level of n-6 polyunsaturated fatty acids (n-6 PUFA), and particularly by a very high augmentation of 22:5 n-6. The ratio n-6 PUFA/n-3 PUFA in liver phospholipids and in serum lipids was a good index of the adequacy of dietary n-3 PUFA supply. However, the ratio 22:5 n-6/22:6 n-3 was a finer index. This ratio appeared to be a reliable index of dietary n-3 PUFA deficiency when it was higher than 1 in serum lipids of a fasting animal. The proportion of 22:5 n-6 as well as the ratios n-6/n-3 and 22:5 n-6/22:6 n-3, were also increased in the liver phospholipids of lactating females receiving the soya oil diet; this suggested that a supply of 130 mg/100 g of diet, corresponding to a ratio of n-6/n-3 = 7.2, was not sufficient for these rats during pregnancy and lactation. A supply of 200 mg of n-3 PUFA/100 g of diet, corresponding to a ratio of n-6/n-3 = 5, is recommended for these animals.
Animals↗
Alteration in fatty acid composition of adult rat brain capillaries and choroid plexus induced by a diet deficient in n-3 fatty acids: slow recovery after substitution with a nondeficient diet.
Wistar rats were fed for three generations with a semisynthetic diet containing either 1.5% sunflower oil (940 mg% of C18:2n-6, 6 mg% of C18:3n-3) or 1.9% soya oil (940 mg% of C18:2n-6, 130 mg% of C18:3n-3). At 60 days of age, the male offspring of the third generation were killed. The fatty acyl composition of isolated capillaries and choroid plexus was determined. The major changes noted in the fatty acid profile of isolated capillaries were a reduction (threefold) in the level of docosahexaenoic acid and, consequently, a fourfold increase in docosapentaenoic acid in sunflower oil-fed animals. The total percentage of polyunsaturated fatty acids was close to that in the soya oil-fed rats, but the ratio of n-3/n-6 fatty acids was reduced by threefold. In the choroid plexus, the C22:6n-3 content was also reduced, but by 2.6-fold, whereas the C22:5n-6 content was increased by 2.3-fold and the ratio of n-3/n-6 fatty acids was reduced by 2.4-fold. When the diet of sunflower oil-fed rats was replaced with a diet containing soya oil at 60 days of age, the recovery in content of n-6 and n-3 fatty acids started immediately after diet substitution; it progressed slowly to reach normal values after 2 months for C22:6n-5 and 2.5 months for C22:6n-3. The recovery in altered fatty acids of choroid plexus was also immediate and very fast. Recovery in content of C22:5n-6 and C22:6n-3 was complete by 46 days after diet substitution.
Animals↗
Slow recovery of the fatty acid composition of sciatic nerve in rats fed a diet initially low in n-3 fatty acids.
The sciatic nerve of rats fed sunflower oil (6 mg 18:3-n-3/100 g of diet) presented dramatic alterations in the long chain polyunsaturated fatty acids in comparison with those fed soy oil (130 mg 18:3n-3/100 g of diet). In both 15-day-old and 60-day-old animals fed sunflower oil, 22:6n-3 (cervonic acid) was four-fold less, 22:5n-6 was 10-fold greater; adrenic acid (22:4n-6) was slightly greater and arachidonic acid (20:4n-6) was close to that in rats fed soy oil. The percentage distribution of total polyunsaturated fatty acids as well as the individual saturated and monounsaturated fatty acids were the same in both groups. When the sunflower oil-fed animals were switched to a soy oil-containing diet for either 15 or 60 days, the percentage distribution of 22:6n-3 increased slowly to reach the control value 2.5 months later. Conversely 22:5n-6 decreased slowly. The decay of 22:5n-6 was more rapid than the increase of 22:6n-3.
Animals↗
A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlorinated biphenyls and DDT.
Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5'-hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome P-450, led to no reduction in total vitamin A content of liver or kidney during the 7 day time-course, administration of 3,3',4,4'-tetrachlorobiphenyl, a toxic PCB and a potent 3-methylcholanthrene-type inducer of cytochrome P-450, resulted in progressively lowered liver vitamin A levels (to 40% of control values by day 7). During this time, kidney total vitamin A content increased 3-fold. The increase in kidney vitamin A (due primarily to increased retinol content) was only equal to 1/40 of total vitamin A which had disappeared from the liver. Although 3,3',4,4'-tetrachlorobiphenyl specifically induced certain drug-metabolizing enzyme activities, e.g. aryl hydrocarbon hydroxylase and UDP-glucuronosyltransferase (toward 4-nitrophenol), no highly significant correlations were found among the vitamin A levels and drug-metabolizing enzyme activities in the liver (aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aldrin epoxidase, microsomal epoxide hydrolase, UDP-glucuronosyltransferase toward 4-nitrophenol, glutathione transferase toward 1-chloro-2,4-dinitrobenzene and cytochrome P-450 content) as determined by multiple linear regression analysis.
Animals↗
[Chlamydia trachomatis perityphlitis, an anatomo-clinical entity? Study of 3 cases].
The authors describe three cases of perityphlitis secondary to Chlamydia trachomatis infection and revealed at laparotomy. Clinically, the symptoms invariably mimicked acute appendicitis. The pathogen was identified by a direct immunofluorescent assay with specific monoclonal antibodies (Microtrak). Prompt cure was achieved by doxycycline therapy. Thus, peroperatively, the discovery of an isolated perityphlitis with a normal appendix should raise the possibility of a C. trachomatis infection, even if there is no salpingitis.
Adult↗
Cyclosporine administration decreases liver vitamin A stores in normal and vitamin A-deficient rats.
Thirty-four Wistar rats were fed a marginal or normal vitamin A diet and received daily for 14 days an intragastric intubation of oil supplemented with 0, 20, or 60 mg X kg-1 of cyclosporine A. The hepatic content and concentration of vitamin A were significantly decreased by cyclosporine treatment, whereas no modification occurred in kidney or serum vitamin A levels. No induction of hepatic cytochrome P-450 was observed in treated animals. These results suggest that cyclosporine interferes with vitamin A stores; thus, vitamin A supplementation may be useful in patients receiving cyclosporine therapy. Drug-metabolizing enzymes, which are cytochrome P-450 dependent, did not seem to be involved in the hepatic vitamin A decrease observed.
Animals↗