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Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 235 records · Page 13Linked to original sources
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

Diet and breast cancer: the possible connection with sugar consumption.

The paper presents an epidemiological study of breast cancer mortality in relation to food consumption. It was found that younger and older women (possibly pre- and post-menopausal women) differ with respect to such correlations. In older women a strong correlation was found between breast cancer mortality and sugar consumption (correlation coefficient = 0.9), and a weaker correlation, possibly of marginal interest, with fat consumption (correlation coefficient = 0.7). In younger women the correlation with diet seems weak. A possible connecting link between sugar consumption and breast cancer is insulin. This is an absolute requirement for the proliferation of normal mammary tissue and experimental mammary tumours may regress in its absence. Insulin secretion occurs in response to blood glucose level and could be excessive if the regulatory mechanism is overtaxed by large sugar intake. The same mechanism might account for the increased risk of mammary cancer in diabetics.

Adult↗
PubMed1983

Schizophrenia: the role of abnormal essential fatty acid and prostaglandin metabolism.

There are two series of essential fatty acids (EFAs), the n6 series starting with linoleic acid and the n3 series starting with alpha-linolenic acid. Members of both series are important in brain structure and can act as precursors for prostaglandin formation. Normally the desaturase enzymes which metabolize EFAs have a higher affinity for the n3 series. It is proposed that in schizophrenia mutant desaturases are present which prefer the n6 series. This change would account for the low levels of linoleic acid, dihomogammalinolenic acid and 1 series prostaglandins which have been reported in schizophrenia. It would also explain the high levels of arachidonic and alpha-linolenic acids and the recently described therapeutic response to alpha-linolenic acid. The abnormal pattern in n6 series EFAs in schizophrenics can almost exactly be imitated in rats by depriving them of n3 EFAs. This is the nearest experimental equivalent to an inability to metabolize EFAs because of an enzyme defect. Heterozygotes carrying such a mutant gene would have an advantage over either form of homozygote since they would be better able to cope with variations in dietary intake of n3 and n6 EFAs.

Animals↗
PubMed1983

The role of essential fatty acids and prostaglandins in the premenstrual syndrome.

Many of the features of the premenstrual syndrome are similar to the effects produced by the injection of prolactin. Some women with the premenstrual syndrome have elevated prolactin levels, but in most the prolactin concentrations are normal. It is possible that women with the syndrome are abnormally sensitive to normal amounts of prolactin. There is evidence that prostaglandin E1, derived from dietary essential fatty acids, is able to attenuate the biologic actions of prolactin and that in the absence of prostaglandin E1 prolactin has exaggerated effects. Attempts were made, therefore, to treat women who had the premenstrual syndrome with gamma-linolenic acid, an essential fatty acid precursor of prostaglandin E1. Gamma-linolenic acid is found in human, but not cows', milk and in evening primrose oil, the preparation used in these studies. Three double-blind, placebo-controlled studies, one large open study on women who had failed other kinds of therapy for the premenstrual syndrome and one large open study on new patients all demonstrated that evening primrose oil is a highly effective treatment for the depression and irritability, the breast pain and tenderness, and the fluid retention associated with the premenstrual syndrome. Nutrients known to increase the conversion of essential fatty acids to prostaglandin E1 include magnesium, pyridoxine, zinc, niacin and ascorbic acid. The clinical success obtained with some of these nutrients may in part relate to their effects on essential fatty acid metabolism.

Clinical Trials as Topic↗
PubMed1982

Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy.

In the plasma phospholipids of a group of 50 young adults with atopic eczema, there was an elevation of cis-linoleic acid associated with a deficit of gamma-linolenic acid and of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. This suggests that atopics have a deficit in the function of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. Carriers of cystic fibrosis tend to be phenotypically atopic, supporting previous suggestions that in homozygote cystic fibrosis patients the key defect may be in the delta-6-desaturase enzyme. Atopic patients may be exceptionally sensitive to side effects of non-steroidal anti-inflammatory agents. They fail to flush in response to application of niacin compounds to the skin, a reaction mediated by prostaglandins. A deficit of prostaglandin precursors would explain both of these observations. That the observed biochemical deficit plays a causative role in the manifestations of atopy was indicated by the fact that in a double-blind, placebo-controlled crossover trial, gamma-linolenic acid in the form of evening primrose oil (Efamol), partially corrected both the biochemical abnormalities and the clinical state.

Dermatitis, Atopic↗
PubMed1981

Interactions between dopamine and prostaglandins on vascular reactivity to noradrenaline: dopamine inhibits the action of PGE1.

Interactions between dopamine and responses to noradrenaline as modulated by prostaglandins (PGs) were studied in the perfused rat mesenteric vascular bed. When perfused alone dopamine up to a concentration of 10(-7)M neither changed baseline pressure nor modified the pressor response to noradrenaline. Dopamine at 10(-9) to 10(-7)M significantly inhibited responses to noradrenaline which had been enhanced by the presence of 10(-10) to 10(-8) M PGE1. In preparations in which vascular responses to noradrenaline had been abolished by indomethacin and restored by adding PGE1, 10(-9) to 10(-7)M dopamine significantly inhibited the restored responses. Dopamine also attenuated the inhibitory effects of prostacyclin on pressor responses to noradrenaline but it did not change the actions of either PGE2 or PGF2 alpha. Pimozide, a mainly centrally acting dopamine antagonist, did not interfere with these peripheral actions of dopamine. The dopamine effects were blocked by another dopamine antagonist, metoclopramide. Dopamine can inhibit the effects of PGE1 and prostacyclin in the rat mesenteric vascular bed, possibly by interacting with specific dopamine receptors.

Alprostadil↗