Linoleic Diet Research Articles

Reversal of brain essential fatty-acid deficiency in the rat by dietary linoleate, linolenate and arachidonate

1. 1. Nineteen-day old rats were fed on an essential fatty-acid deficient diet for 18 weeks, thereby making them essential fatty-acid deficient for at least 5 weeks. The weights of their brains were 20.2% less than those of rats on control diet. 2. 2. When deficient rats were rehabilitated for 5 weeks on a diet supplemented with either linoleate, linolenate or arachidonate, the weights of their brains were 94.3, 88.5 and 92.3%, respectively, of the control value. 3. 3. Essential fatty-acid deficiency was characterized by a large reduction in the proportions of cerebrosides, sphingomyelin and the essential fatty acids and a high increase in the proportion of eicosatrienoic acid (20:3). 4. 4. Rehabilitation for 5 weeks on a diet supplemented with essential fatty acids reversed these changes in brain composition. 5. 5. It is considered that linoleate and arachidonate possess full activity while linolenate possesses only partial activity in reversing essential fatty-acid deficiency syndrome in rat brain.

Role for fatty acid binding protein in the regulation of hepatic lipogenesis by dietary linoleic acid

The effect of added dietary ethyl palmitate or ethyl linoleate on hepatic lipogenic enzymes and the amount of hepatic fatty acid binding protein was examined in meal-fed rats. Dietary linoleate reduced the activities of fatty acid synthetase, glucose-6-phosphate dehydrogenase, NADP-malic enzyme, ATP-citrate lyase, and the amount of fatty acid binding protein compared to rats fed a fat-free or palmitate supplemented diet. The possible role of fatty acid biding protein in the regulation of lipogenesis by dietary fat is discussed.

Effects of Dietary Essential Fatty Acid Concentration upon Prostanoid Synthesis in Rats

The effects of dietary linoleate as zero to 27% of energy, fed to female rats for 6 months, in relation to ability of whole blood to synthesize PG during clotting at 37 degrees was studied. Synthesis of PGE1, PGE2, PGF2 apha and TXB2 after 10 or 40 minutes of incubation of whole blood was determined by assay of serum concentration by radioimmunoassay. Fatty acid composition of serum phospholipids, cholesteryl esters and acyl glycerides was determined. PG synthesis increased with linoleate as zero to 2% of kcal; from 2% up to 7% there was a decrease of PG synthesis; from 7% to 27% there was a linear increase. There was no pattern to PGF2 alpha maximum concentration. PGE2 had a linear increase from 0 to 30% linoleate. PGE1 decreased with 0 to 2% linoleate, then increased between 2 and 7% and maintained a plateau through 27%. The concentration of TXB2 was found to be about 20-40 times that of PGE2 and PGF2 alpha. The decline of PGE1 synthesis with 2-7% linoleate calories was correlated with 20:3n-6 concentration and PGE2 and PGF2 alpha production with 20:4. With dietary linoleate concentrations greater than 7.4% PG synthesis had a linear increase up to 27% of kilocalories, not correlated with fatty acids.

Decreased formation of porstaglandins derived from arachidonic acid by dietary linolenate in rats

Accumulated evidence now suggests that availability of precursor acid is an important factor controlling the biosynthesis of prostaglandins (PG's). Since linolenic acid inhibits the conversion of linoleic acid to arachidonic acid (PGE2, PGF2 alpha, and thromboxane A2 precursor), rats receiving more linolenic acid are expected to have less arachidonic acid and thus less PG's synthesized from arachidonic acid than those receiving linoleic acid alone. Essential fatty acid-deficient rats, induced by feeding hydrogenated coconut oil diet for 15 weeks, were divided into six groups and fed graded amounts of purified methyl linolenate for 6 weeks. Each group of rats except essential fatty acid-deficient group received the same amount of linoleate. The results showed that the level of arachidonic acid in serum lipids and serum concentrations of PG's synthesized from arachidonic acid by platelets decreased as the amount of dietary linolenate increased. This indicated that biosynthesis of PG's in platelets can be influenced by the availability of precursors, and thus it can be modified by the manipulation of dietary fatty acids.

Structural and metabolic alterations of lung phosphatidylcholines by essential fatty acid deficiency.

The influences of early changes in essential fatty acid deficiency on the structure and metabolism of lung phosphatidylcholine were studied. In addition to general characteristics observed due to essential fatty acid deficiency such as significant decreases in linoleate and arachidonate, and concomitant increases in oleate and eicosatrienoate, a pronounced decrease in palmitate was noted in lung phosphatidylcholine, particularly in the 2-position. The decrease of palmitate in lung phosphatidylcholine was due to a similar decrease in disaturated classes, particularly in the dipalmitoyl species. These structural changes in phosphatidylcholine were found to be more significant in alveolar wash than in lung parenchyma and lamellar body fractions. The specific activities of phosphatidylcholine and its disaturated classes in lung parenchyma and alveolar wash were significantly lower in the deficient state than in the controls at 2, 6, and 12 hr after the injection of [9,10(-3)H]palmitate. However, relatively more of the phosphatidylcholine in the deficient state appeared in the alveolar space, disappearing more rapidly from the alveolar space than did the phosphatidylcholine in the controls. These results suggest that dietary linoleate may be a factor in regulating the amount of disaturated phosphatidylcholine in the lung, a principal component of lung surfactant, and also a factor in controlling the metabolism of alveolar phosphatidylcholine.

Effect of increased dietary linoleate upon blood pressure, platelet function and serum lipids in hypertensive adult humans: A. I. Fleischman, Atherosclerosis Research Group, New Jersey State Department of Health, Montclair, New Jersey, USA; P.B. Watson; A. Stier; H. Somol; M.L. Bierenbaum

Effect of increased dietary linoleate upon blood pressure, platelet function and serum lipids in hypertensive adult humans: A. I. Fleischman, Atherosclerosis Research Group, New Jersey State Department of Health, Montclair, New Jersey, USA; P.B. Watson; A. Stier; H. Somol; M.L. Bierenbaum

The effects of trans linoleic acid on the concentration of serum prostaglandin f 2α and platelet aggregation

In order to determine the effects of dietary trans linoleate on the concentration of PGF 2α and its precursor acid, and on platelet aggregation, four groups of rats were fed a diet containing hydrogenated coconut oil (HCO, treatment A); 9 trans, 12 trans linoleate (trans linoleate, treatment B); an equal mixture of 9 cis linoleate (cis linoleate) and trans linoleate (treatment C); and cis linoleate (treatment D); respectively for 12 weeks. The levels of arachidonic acid as a percent of total serum lipids were 5.8, 0.8, 25.2 and 30.0, respectively for treatments A, B, C, and D. The serum concentrations of PGF 2α were 3.2, 0.31, 14.1 and 27.4 ng/ml, respectively for treatments A, B, C, and D. Thus, trans linoleate caused decreased biosynthesis of PGF 2α probably resulting from decreased level of its precursor acid. The magnitude of the inhibition of the platelet aggregation by indomethacin was greater in treatment A than in treatment B. The difference in the magnitude of the inhibition between treatment C and D was not apparent at a high concentration of indomethacin, however, at a lower concentration (0.01 mM) the percent inhibition was 3 and 42 for treatments C and D, respectively. These results indicate that levels of dietary linoleate can affect physiological responses through an effect on the amount of PG synthesized in animal tissues.

Dietary fat saturation, mortality and heart and lung morphology of rats

Rats of both sexes were fed diets containing 21% (wt) fat as beef tallow (BT), safflower oil (SO), or a 60:40 BT:SO mix (M). Some of each group were killed at 9, 12, 15, 18, and 21 months of age. Death by 15 months was significantly (P<.001) greater in SO rats than in other groups. Mortality in SO females was significantly (P<.005) greater than in SO males. A trend for longer life existed in M compared to BT rats. Platelet aggregation microscopically visible in the alveoli of SO males and thrombi in the pulmonary arteries of SO females suggest that death in these animals may have been related to dietary linoleate. Excessive production of prostaglandins may have induced platelet aggregation and possibly interfered with normal immune responses. Myocardial stellate scars were seen earlier in M males than in other groups. Areas of massive infarction and subsequent fibrosis of the heart were present in BT rats and M males at 15 months but not until 18 months in M females.

Dietary linoleate effect upon prostaglandin and thromboxane synthesis: Melvin M. Mathias, Karen Fine, Barbara Lipinski, and Jacqueline Dupont, Department of Food Science and Nutrition, Colorado State University, Fort Collins Colorado 80523

Dietary linoleate effect upon prostaglandin and thromboxane synthesis: Melvin M. Mathias, Karen Fine, Barbara Lipinski, and Jacqueline Dupont, Department of Food Science and Nutrition, Colorado State University, Fort Collins Colorado 80523

Effect of different levels of dietary alpha-tocopherol and linoleate on plasma and liver lipids in rats.

The influences of dietary alpha-tocopherol, in combination with three different levels of linoleate (low, moderate or high levels), on the concentrations of plasma and liver lipids in rats were examined. Male Wister rats were fed diets ad libitum for 2 weeks. dl-alpha-Tocopheryl acetate was added to the diets in 0, 20 or 200 mg tocopherol/100 g diet. The following results were obtained. (1) Higher dietary levels of alpha-tocopherol tended to cause higher plasma lipid levels in proportion to the amounts added. This phenomenon is most remarkable in rats fed a diet containing cholesterol and low linoleate (0.8% of calorie). (2) The concentrations of plasma lipids were influenced significantly than those of liver lipids by the levels of alpha-tocopherol under the conditions of this experiment.

The effect of dietary lipid peroxides, sterols and oxidised sterols on cytochrome P450 and oxidative demethylation in the endoplasmic reticulum

The effects of dietary linoleate, oxidised linoleate, lipid peroxides, cholesterol, cholesterol hydroperoxides and squalene have been examined on the concentration of cytochrome P450 and rate of oxidative demethylation in the endoplasmic reticulum. Addition of methyl linoleate (5%) to a diet containing 5% lard caused a large increase in the rate of oxidative demethylation, oxidised methyl linoleate (5%) was much less effective and also depressed the rate of oxidation when added to a diet containing corn oil. A supply of dietary linoleic acid or other polyunsaturated fatty acids are essential for maximum rate of oxidative demethylation in the endoplasmic reticulum and for maximum induction by phenobarbitone. Dietary lipid peroxide did not increase the rate of oxidative metabolism in the endoplasmic reticulum or its induction. Feeding a diet which included 10% herring oil, and which contains only 1.7% linoleic acid caused a very rapid rate of oxidative demethylation and a high concentration of cytochrome P450 in the liver endoplasmic reticulum. Induction by phenobarbitone was also very effective after feeding this diet. The unsaponifiable fraction of herring oil, added to the lard diet, very effectively increased the rate of oxidative demethylation to a value similar to that observed after feeding a diet containing 10% herring oil. Addition of cholesterol (2 g/kg diet) or of squalene (1 g/kg diet) to diets containing 10% lard were less effective than the unsaponifiable fraction of herring oil but caused a large increase in the content of cytochrome P450 and rate of oxidative demethylation in the endoplasmic reticulum. Induction of phenobarbitone was also enhanced. Cholesterol hydroperoxide was not more effective than cholesterol. It may be concluded that a supply of dietary sterols is essential for maximum activity of oxidative demethylation in the liver endoplasmic reticulum, especially when linoleic acid is in restricted supply and for maximum induction by phenobarbitone. The non-saponifiable fraction of herring oil cannot be completely replaced in the diet by pure cholesterol, cholesterol hydroperoxide or squalene.

Effect of dietary linoleate on synthesis and degradation of fatty acid synthetase from rat liver.

The induction of fatty acid synthetase activity in rat liver is markedly reduced by feeding a diet containing a source of linoleate. Within 48 h after changing from a fat-free, high carbohydrate diet to one containing 15% by weight of safflower oil, the specific activity of rat liver fatty acid synthetase is approximately 2-fold lower than that from rats fed a fat-free diet througout. In contrast, feeding a diet containing 15% hydrogenated coconut oil, a source of saturated fatty acids, or 5% methyl oleate for the same length of time has little effect on the activity of the enzyme. The rate of synthesis of the enzyme is reduced by safflower oil feeding from the fat-free (control) level and after 48 h is approximately one-half that of the control. The rate of degradation of fatty acid synthetase is markedly increased in the safflower oil-fed animals over the control; the half-lives are 1.8 days and 3.8 days, respectively. It is suggested that polyunsaturated fatty acids, or a product derived from them, may directly or indirectly regulate the transcription or translation (or both) of fatty acid synthetase messenger RNA.

Metabolism of fatty acids in fish. I. Development of essential fatty acid deficiency in the carp, Cyprinus carpio Linnaeus 1758

Carp, 15–25 g in weight, were maintained on diets containing linolenic acid in various concentrations (0.5, 1.0, 3.4 and 11.1 mg/g food) for 4 weeks and the fatty acid composition of liver total lipids as well as that of liver triglycerides and phospholipids was determined. The fish ingesting the diet containing 1.1% linolenate accumulated only negligible amounts of 20:3 ω 9 and exhibited a low ratio of 20:3 ω 9 to 22:6 ω 3 (0.07) in the total lipid. This ratio increased from 0.33 to 2.00 in liver total lipids of fish ingesting 3.4, 1.0 and 0.5 mg linolenic acid in 1 g of food. This effect was more pronounced in the phospholipids. The level of oleic acid in triglycerides was inversely related to the concentration of linolenic acid in the diet. Linoleic acid at a concentration of 13–16 mg/g food was unable to prevent the accumulation of 20:3 ω 9 in the lipids of fish ingesting diets containing a low level of linolenate. The possible effects of dietary linolenate on the fatty acid metabolism of fish are discussed.

Stimulation of hepatic lipogenesis by eicosa‐5,8,11,14‐tetraynoic acid in mice fed a high linoleate diet

Liver slices, from mice fasted for one day and then refed for three days either a 15% corn oil diet or a 15% corn oil diet containing eicosa-5,8,11,14-tetraynoic acid (TYA), were incubated with [1-14C] acetate or [3H] H2O to determine lipogenic capacity. Dietary TYA produced a twofold stimulation in fatty acid and cholesterol synthesis. TYA also caused an increase in the relative proportion of linoleate (C18:2) and a decrease in that of arachidonate (C20:4) in liver. Thus, (a) despite high levels of C18:2, hepatic lipogenesis can be increased, and (b) even short term feeding of TYA can alter the hepatic fatty acid composition presumably by inhibition of arachidonate synthesis from linoleate.

Influence of fasting-refeeding and dietary linoleate on liver glucose-6-phosphate dehydrogenase and phospholipid fatty acid composition in rats adapted to a purified diet.

Responses to refeeding after fasting were studied in male rats fed a purified casein-sucrose diet containing 5% safflower oil. After a 48 hr fast, the rats were fed either the same diet or the same diet minus oil (fat-free diet). These experiments were designed to distinguish changes due to fasting and refeeding alone without a change of diet from those changes caused by refeeding a diet of different composition. In the first experiment, rats were refed for 3 or 7 days. In rats refed either diet, liver glucose-6-phosphate dehydrogenase (G6PD) activity was elevated above refasting levels, but after 7 days, activity in rats refed the 5% safflower oil diet was significantly lower than in those refed the fat-free diet. The amount of liver arachidonate in rats refed the safflower oil diet was the same during refeeding as before fasting. In the second experiment, rats were refed the fat-free diet for 1, 2, 3, or 7 days. Liver G6PD and fatty acid synthetase were measured, as well as fatty acids in liver total lipids and phospholipids. G6PD activity increased above prefasting levels after one day refeeding and continued to increase for 7 days. Fatty acid synthetase activity increased for the first 3 days of refeeding, with no additional increase after 7 days. In all rats refed the fat-free diet, the proportions of arachidonate and linoleate in liver phospholipids diminished with time, and eicosatrienoate appeared. These results show that (a) maintenance of liver phospholipid arachidonate did not prevent increased G6PD activity in early refeeding, but the elevated G6PD activity later declined when phospholipid arachidonate was maintained by feeding a source of linoleate; (b) the metabolic state of fasted-refed rats had not returned to prefasting conditions even after 7 days of refeeding a linoleate-rich diet to which the rats were adapted before fasting.

Reduced growth rate of transplantable mammary adenocarcinoma in C3H mice fed eicosa-5,8,11,14-tetraynoic acid.

Female 3-month-old C3H mice were given sc injections of 5-mg pieces of mammary adenocarcinoma and fed a linoleate-containing (15% corn oil) diet in the presence or absence of eicosa-5,8,11,14-tetraynoic acid (TYA), an inhibitor of prostaglandin synthesis. After 6 weeks, the weights of tumors of mice fed the TYA-free linoleate diet were three to five times greater than those of mice fed the TYA-containing linoleate diet. Dietary TYA caused a reduction in the levels of arachidonate and an elevation in the levels of linoleate in mammary tumors and livers. Aspirin, another known inhibitor of prostaglandin synthesis, when added to the linoleate diet, did not affect the tumor size or the composition of fatty acids in the tumors and livers. Thus we concluded that a) the growth of mammary tumors was not related to prostaglandin synthesis but was related to the availability of arachidonate, and b) TYA was an effective inhibitor for the conversion of linoleate to arachidonate.

Effects of chronic ethanol administration in the rat: relative dependency on dietary lipids. II. Paradoxical role of linoleate in the induction of hepatic drug-metabolizing enzymes in vitro

The effect of chronic ethanol administration on the hepatic microsomal cytochrome P-450 content and activities of NADPH - cytochrome P-450 reductase (EC 1.6.2.4), benzphetamine demethylase, aniline hydroxylase (EC 1.14.14.1), and of the microsomal ethanoloxidizing system were studied in various dietary models. When ethanol was given with linoleate as the only source of dietary lipid, the ethanol induction of these parameters was greater with diets containing 2 or 5% of total calories as linoleate than with diets containing 10% of total calories as linoleate. By contrast, when ethanol was given with high fat (35% of total calories) diets, the ethanol induction of these same parameters was slightly greater when linoleate provided 10% of total calories than when it provided 3% of calories. The apparent effect of dietary linoleate on the induction, by ethanol, of microsomal drug-metabolizing enzymes is markedly different when linoleate is given as the only source of dietary lipid as opposed to when it is given with other dietary lipids. Thus, conclusions on the effect of ethanol on hepatic microsomal drug-biotransformation enzymes, drawn from studies with dietary models in which linoleate provides the only source of dietary lipid, connot be extended to dietary modles of more complex lipid composition. When given as the only source of lipid, 2% of total calories in linoleate appears optimal for basal activity and inductibility, by ethanol, of mixed-function oxidases.

Dietary fatty acids and arterial thrombosis: effects and mechanism of action with special reference to linoleic acid.

In rats dietary long-chain saturated fatty acids with more than 14 carbon atoms promote arterial thrombus formation, whereas dietary linoleate has a specific antithrombotic effect. The dietary fat effects are not mediated by changes in coagulation but are most probably caused by changes in the aggregation tendency of blood platelets.

Effect of .ALPHA.-tocopherol deficiency on carp. VII. The relationship between dietary levels of linoleate and .ALPHA.-tocopherol requirement.

Feeding experiments were conducted to investigate the relationship between the requirement for tocopherol and dietary linoleate levels in carp. The results obtained in the feeding experiments showed that the elevated dietary linoleate levels increase the tocopherol requirement of carp, judging from the appearance of apparent muscular dystrophy. The fish receiving the diet with α-tocopherol content less than 10mg per 100g diet at the 5% linoleate level showed apparent muscular dystrophy and gained less body weight than those receiving diets enriched with the vitamin at levels exceeding 30mg per 100g diet. The weight gain of the carp receiving from 10-15% linoleate at a fixed level of 10mg α-tocopherol was low and 35-40% of the fish exhibited apparent muscular dystrophy. The fat-free and α-tocopherol deficient diets resulted in decreases in 18:2ω6, 20:4ω6 and 22:5ω6, the former diet also result in a marked increase of 16:1, 18:1 and 20:3ω9. Linoleic acid supplements gave increases in 18:2ω6, 20:4ω6 and 22:5ω6 and decreases in 16:1, 18:1 and 20:3ω9, while there were no marked changes in fatty acid distribution attributable to presence of increasing levels of tocopherol in the diet.

In vivo platelet function in diabetes mellitus

In vivo platelet aggregation time is significantly shorter in diabetics compared to age and sex matched controls. A significantly greater number of the diabetic subjects failed to disaggregate. In a geriatric diabetic population, increasing absorbed dietary linoleate lengthened aggregation time so that the aggregation time was not significantly different from the control population. Similarly, increased absorbed dietary linoleate significantly improved platelet disaggregation in diabetic subjects.