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Biomedical subjects

M S Manku

Publications and source records attributed to M S Manku.

At least 55 records · Page 3Linked to original sources

Contrasting effects of low or high copper intake on rat tissue lipid essential fatty acid composition.

The effects of low copper intake or copper supplementation on the metabolism of stearic acid have been studied previously, but their effects on essential fatty acids have not been reported. Male Sprague-Dawley rats were fed for 12 weeks on pelleted semi-synthetic diets containing less than 1 mg/kg copper (low copper), 6 mg/kg (copper control), or 250 mg/kg copper (copper supplemented). The fatty acid composition of the total phopholipids and triglycerides of plasma, liver, heart and adipose tissue was analyzed by gas liquid chromatography. In low copper rats compared to controls, palmitic and oleic acids were decreased but stearic acid and docosahexaenoic acid were increased in plasma, liver and heart phopholipids. Arachidonic acid was also increased in plasma and liver phospholipids in low copper rats. In liver triglycerides, linoleic and arachidonic acids were increased but palmitic and oleic acid were decreased in low copper rats. Copper supplementation had the opposite effect; palmitic and oleic acids were increased in phospholipids and triglycerides whereas essential fatty acids were generally decreased. Hence, copper not only has a direct effect on the desaturation of stearic acid but also has significant effects on the tissue lipid composition of essential fatty acids.

Adipose Tissue↗

Effect of ethanol on liver triglycerides and fatty acid composition in the golden Syrian hamster.

In choice situations, the golden Syrian hamster shows a strong preference to drink an ethanol solution to water alone. Because of the known effects of ethanol on lipid metabolism, its effects on liver fatty acids were therefore studied in the hamster. After a period of 8 weeks during which hamsters had consumed water containing 10% ethanol (4 weeks) and then 15% ethanol (4 weeks), the liver was significantly increased in weight, an effect which was shown to be due to fat accumulation as triglyceride. The fatty acid composition of the liver triglycerides and phospholipids was altered such that monounsaturated fatty acids were very significantly increased and both n-6 and n-3 essential fatty acids were proportionally decreased.

Animals↗

Effect of dietary alpha- and gamma-linolenic acid on tissue fatty acids in guinea pigs.

Guinea pigs were fed regular chow diets supplemented with 5% (by weight) safflower oil, evening primrose oil, or linseed oil for 6 weeks. The unsaturated fatty acid content of these oils was 78.9% of 18:2n6, 74.1% of 18:2n6, and 9.2% of 18:3n6, or 21.5% of 18:2n6 and 46.9% of 18:3n3, respectively. In comparison with 18:2n6, dietary supplementation with 18:3n6 significantly increased the tissue levels of 18:3n6 and 20:3n6, whereas dietary 18:3n3 significantly elevated the levels of 18:3n3 in plasma and liver lipids. Dietary 18:3n3 also significantly increased 22:5n3 and 22:6n3 in total phospholipids. The tissue levels of 20:4n6, on the other hand, were not affected by either treatment. These data suggest that both delta 6- and delta 5 desaturation of n-6 fatty acids in guinea pigs are low, and that the metabolism of n-3 and n-6 fatty acids may be regulated by two different enzyme systems.

Animals↗

Short-term effect of dietary cholesterol on tissue n-6 fatty acids in fat-deficient rats.

Weanling female rats raised on a fat-free diet for 8 weeks were then given the same diet supplemented with 0, 0.25, 0.5, or 1% by weight of cholesterol in addition to 10% of safflower oil for 3 days. Fatty acid compositions of cholesteryl esters (CE), triglycerides (TG), and phospholipids (PL) in liver and plasma were examined. Cholesterol feeding increased plasma and liver cholesterol contents and also affected the patterns of n-6 polyunsaturated fatty acids. There were no consistent changes in either plasma and liver TG which contained little 20:3n-6 and 20:4n-6. The levels of 20:3n-6 increased in plasma and liver PL, while proportions of 20:4n-6 decreased in liver and plasma CE. However, the absolute amount of 20:4n-6 in cholesteryl esters increased because of a threefold rise in cholesteryl ester levels. The changes might be attributable to an increased utilization of 20:4n-6 for cholesterol transport and/or an inhibition of delta 5-desaturation of n-6 fatty acids by cholesterol feeding.

Adipose Tissue↗

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

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

Adult↗

Essential fatty acids in plasma, red blood cells and liver phospholipids in common laboratory animals as compared to humans.

Essential fatty acids were estimated in plasma, red blood cells and liver total phospholipids in rats, mice, hamsters, guinea pigs, rabbits and humans. There were large species differences, suggesting that different species levels should be borne in mind when choosing an animal for a particular study. The 2 species most susceptible to atheroma, the guinea pig and the rabbit, had very high levels of linoleic acid and low levels of linoleic acid metabolites. n-3 fatty acid levels were low in guinea pigs and rabbits and the ratio of n-3 to n-6 fatty acids also was low in the rat. Mice and hamsters had the highest n-3 levels, suggesting they may be the best species to use for studies on the roles of n-3 essential fatty acids. Mice and hamsters and, in some respect rats, were closest to humans in their fatty acid patterns.

Animals↗

The effects of dietary cholesterol on blood and liver polyunsaturated fatty acids and on plasma cholesterol in rats fed various types of fatty acid diet.

Male rats were fed on a fat-free diet for 8 weeks and then switched to diets containing 10% hydrogenated coconut oil (HCO), safflower oil (SFO) or evening primrose oil (EPO). Half of each group was also given 1% of cholesterol in the diet. After 5 further weeks, plasma, red cell and liver fatty acids were measured in the various lipid fractions. Plasma and liver cholesterol also were estimated. In almost all fractions and on all three diets, feeding cholesterol led to accumulation of the substrates of desaturation reactions and to deficits of the products of these reactions. The results were consistent with inhibition of delta-6, delta-5 and delta-4 desaturation of n-6 essential fatty acids. Since the diets were deficient in n-3 fatty acids, levels were very low but were also consistent with inhibition of desaturation. In contrast, cholesterol had relatively less consistent effects on 20:3n-9, suggesting that desaturation of n-9 fatty acids was less inhibited. Plasma cholesterol levels rose sharply in the HCO and SFO groups but not at all in the EPO group. EPO contains the product of delta-6-desaturation, 18:3n-6, suggesting that conversion of linoleic acid to 18:3n-6 and possibly to further metabolites may be important for the cholesterol-lowering effect of polyunsaturates.

Animals↗

Tissue phospholipid fatty acid composition in the diabetic rat.

Tissue phospholipid fatty acid compositions in streptozotocin-induced diabetic rats were studied. The major changes in liver, plasma, erythrocyte and heart were increased proportions of linoleic and dihomo-gamma-linolenic acids and a decreased proportion of arachidonic acid. The latter was not significantly changed in phospholipids of kidney, adrenal gland and testis. Skin fatty acids in diabetic rats showed an increase in the proportion of arachidonic acid and a reduction in the proportion of linoleic acid. The fatty acid desaturating activity in diabetes may be regulated differently in different tissues.

Adrenal Glands↗

Effect of dietary depletion and repletion of linoleic acid on renal fatty acid composition and urinary prostaglandin excretion.

To study the effect of dietary modification on urinary prostaglandin E (UPGE) excretion and on renal fatty acid compositions, weanling male rats were raised on a fat-free diet for 6 weeks and were switched to a diet containing 2 energy % of linoleic acid (LA) for 8 days. During fat deprivation, UPGE excretion increased in the first week (6.9 ng/24 hours urine), fell to a minimum of 1.1 ng/24 hours at 3rd week and thereafter remained at a level lower than that in the controls (3.1 ng/24 hours). UPGE excretion returned rapidly to normal (2.7 ng/hr) only 24 hours after LA supplementation. During LA treatment, arachidonic acid (AA) concentrations in renal cholesteryl esters rapidly increased from 19% to 27% (33% in the controls), while concentrations in renal phospholipids (PL) and renal free fatty acids (FFA) did not change during the first four days but reached the normal range at the 8th day. The present studies demonstrate that chronically fat deficient animals excreted significantly less UPGE than that in the controls. However, this deficiency could be rapidly reversed by LA supplementation despite the fact that AA levels in renal lipid fractions remained well below normal. This suggests that dietary LA may be rapidly converted to AA and subsequently to PGE without AA levels rising in the lipid fractions usually thought of as being PG precursors.

Animals↗

Prostaglandin precursors in plasma phospholipids of patients with psoriasis: effects of treatment with coal tar.

Plasma phospholipids of patients with psoriasis have significantly reduced levels of dihomogammalinolenic acid (20:3n-6), arachidonic acid (20:4n-6) and adrenic acid (22:4n-6), the precursors of the 1, 2 and homo-2 series of prostaglandins (PGs). Concentrations of the 3 series PG precursor, eicosapentaenoic acid (20:5n-3) were normal. Hospital treatment with a coal tar regime produced a rise in 20:3n-6 to levels which were significantly above normal.

8,11,14-Eicosatrienoic Acid↗

Accumulation of linoleic and gamma-linolenic acids in tissue lipids of pyridoxine-deficient rats.

Young male Sprague-Dawley rats were fed diets containing added pyridoxine . HCl at 22 mg/kg (control), 0 mg/kg or 88 mg/kg for 6 weeks. In comparison with control or pyridoxine-supplemented (+PN) rats, growth of the pyridoxine-deficient (-PN) rats was significantly less after 2 weeks. After 6 weeks, liver weight was higher but thymus and epididymal fat weights, in relation to body weight, were significantly lower in -PN compared to control rats. In -PN rats, phospholipid levels of linoleic and gamma-linolenic acids were increased, but arachidonic acid was decreased compared to controls in plasma, liver, thymus and skin. In liver triglycerides from -PN rats, all essential fatty acids (n3 and n6) were increased compared to both control and +PN rats. The n3 essential fatty acids were significantly increased in plasma, liver, and thymus phospholipids in the +PN compared to control rats. These results support previous reports of an effect of pyridoxine on essential fatty acid metabolism and suggest that both linoleic desaturation and gamma-linolenic acid elongation may be impaired in -PN rats. In addition, the accumulation of essential fatty acids in the liver triglycerides of -PN rats suggests that essential fatty acid turnover between triglyceride and phospholipid may be influenced by pyridoxine.

Adipose Tissue↗

Essential fatty acids in the plasma phospholipids of patients with atopic eczema.

We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.

Adult↗

Essential fatty acids in tissue phospholipids and triglycerides of the zinc-deficient rat.

This study addressed the possibility that zinc deficiency has different effects on the fatty acid composition of triglyceride compared to total phospholipid. Male weanling Sprague-Dawley rats were maintained for 6 weeks on a semisynthetic diet deficient in zinc (3 mg/kg zinc). Control rats (40 mg/kg zinc) were pair-fed. Lipid fractionation and fatty acid analysis were by thin-layer and gas chromatography, respectively. In zinc-deficient rats, the percentage of linoleic acid was increased or that of arachidonic acid was decreased in total phospholipids of plasma, liver, and testis, and in skin total lipids. Saturated and monounsaturated fatty acids were increased in the triglyceride of liver but decreased in the triglyceride of epididymal fat of zinc deficient rats. Essential fatty acids, as a proportion of total fatty acids, were decreased in triglyceride of liver but increased in triglyceride of epididymal fat of zinc-deficient rats. Our fatty acid data from tissue total phospholipids therefore support the concept that linoleic acid desaturation is impaired in zinc deficiency.

Adipose Tissue↗

Effects of essential fatty acids on prostaglandin biosynthesis.

Prostaglandins (PGs) are derived from dietary essential fatty acids (EFAs) by relatively short biochemical pathways. PG synthesis can be manipulated by modifying EFA intake. PGs and related compounds of the 1 and 3 series have desirable or neutral actions while those of the 2 series are mixed, some being desirable but others being highly undesirable. Methods for selectively increasing 1 and 3 series products while simultaneously reducing the formation of arachidonic acid derivatives are described.

Animals↗

Fatty acids in plasma and red cell membranes in normal humans.

A detailed study was made of the fatty acid composition of plasma triglycerides, free fatty acids, phospholipids, red cell total phospholipids, phosphatidylcholine and phosphatidylethanolamine in 32 normal males and 18 normal females. No sex differences could be detected. There were substantial differences in the compositions of the various fractions and long-chain polyunsaturated fatty acids were particularly important in the red cells.

Adult↗

How do polyunsaturated fatty acids lower plasma cholesterol levels?

For 30 years it has been known that linoleic acid can lower elevated cholesterol levels. Large increases in linoleic acid have been widely recommended as a way of reducing the risk of cardiovascular disease. Such recommendations have resulted in major dietary shifts in some countries, including the USA. Yet the precise characteristics of the linoleic acid molecule which confer on it cholesterol-lowering properties are unknown. gamma-Linolenic acid, the first essential fatty acid metabolite of linoleic acid, has been found to have cholesterol-lowering actions ca. 170 times greater than the parent molecule, suggesting that linoleic acid must be converted to gamma-linolenic acid to exert its desirable effects on cholesterol metabolism. Aging, sex, diabetes mellitus, alcohol, catecholamines and trans fatty acids and saturated fats can all modulate the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. This provides a possible unifying explanation for the actions of these known risk factors for cardiovascular disease.

Adolescent↗