PubMed Health⌕ Search

Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 217 records · Page 12Linked to original sources
PubMed1985

Selective killing of human cancer cells by polyunsaturated fatty acids.

Polyunsaturated fatty acids killed incubated human breast, lung and prostate cancer cells at concentrations which had no adverse effects on normal human fibroblasts or on normal animal cell lines. The most consistent and selective effects were obtained with fatty acids containing 3, 4 and 5 double bonds. When human cancer cells and normal human fibroblasts were co-cultured in the absence of polyunsaturated fatty acids, the malignant cells overgrew the normal ones. When eicosapentaenoic acid (EPA, 20:5n-3), gamma-linolenic acid (GLA, 18:3n-6) or arachidonic acid (AA, 20:4n-6) were added to the co-cultures, the normal cells outgrew the malignant ones. These observations suggest that treatment of malignancy with polyunsaturated fatty acids may have considerable potential while being associated with a high level of safety.

Animals↗
PubMed1985

Essential fatty acids in the liver and adipose tissue of genetically obese mice: effect of supplemental linoleic and gamma-linolenic acids.

Genetically obese mice (ob/ob) and their lean litter-mates were given diets iso-energetically supplemented with sucrose, hydrogenated coconut oil, safflower oil or evening primrose (Oenothera biennis) oil. Weight gain over 15 weeks was significantly greater in the evening primrose oil-supplemented obese mice than in the other groups. In all the groups of obese mice, liver total phospholipids contained proportionally less linoleic acid and more dihomo-gamma-linolenic acid and arachidonic acid than did the lean controls. As a percentage of total fatty acids, n-3 essential fatty acids (EFA) in liver and adipose tissue lipids were significantly lower in the obese mice than in the lean controls. Supplementation with EFA-rich oils (safflower and evening primrose oil) increased the proportional composition of n-6 EFA and decreased the n-3 EFA more in the liver total phospholipids of the lean than the obese mice.

Adipose Tissue↗
PubMed1985

Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids.

Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

Animals↗
PubMed1985

Magnesium deficiency in the rat increases tissue levels of docosahexaenoic acid.

The effects of magnesium deficiency on tissue levels of total lipids and fatty acids were evaluated. Sprague-Dawley rats were fed a magnesium-deficient diet for 14 wk with controls being pair-fed to the deficient rats. Compared to the controls, serum and 24-h urinary magnesium levels were markedly lower in the magnesium-deficient rats. Serum cholesterol and total phospholipids were significantly higher in the magnesium-deficient rats than in the controls. Edema and polycystic degeneration of the kidneys were present in the magnesium-deficient rats. Kidney total phospholipids and triacylglycerols were significantly lower in the magnesium-deficient rats than in the controls. The main change in tissue fatty acid composition in magnesium deficiency was the higher docosahexaenoic acid (22:6n-3) in serum, liver and aorta than in controls. The possible relationship of these findings to human alcoholism is discussed.

Animals↗
PubMed1985

The effects of hydrogenated coconut oil, safflower oil, and evening primrose oil on development of hypertension and sodium handling in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) were fed a basal regular diet (BD) or three different fat-supplemented diets which contained 10% hydrogenated coconut oil (HCO), 10% safflower oil (SFO), or 10% evening primrose oil (EPO). The rats received these four different diets from 4 weeks to over 24 weeks of age. The development of hypertension in SHR was significantly retarded in the EPO-supplemented animals. The blood pressure was lower in the SFO group animals as compared with the BD and HCO groups, but this did not reach significance. Sodium excretion rate in young SHR was increased in the EPO group compared with the HCO and SFO groups, and the urinary K/Na ratio was decreased in the EPO group compared with the HCO and EPO groups. Water intake and urine volume were increased in the SFO group as compared with the HCO and EPO groups. Sodium concentration in erythrocytes was decreased in the rats receiving SFO. Pressor responses to norepinephrine and angiotensin II were enhanced in the EPO and SFO groups as compared with the basal chow group. These data suggest that a dietary supplementation of EPO which contains a substantial amount of gamma-linolenic acid consistently lowers blood pressure in SHR. The mechanism is uncertain, but the effects on sodium handling may in part be responsible for the retardation of the development of hypertension. There was a difference between the EPO and the SFO groups in sodium--water handling, and to some extent in the blood pressure development in SHR.

Angiotensin II↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

Essential fatty acid metabolism in diseases of connective tissue with special reference to scleroderma and to Sjogren's syndrome.

Drugs which modify the conversion of essential fatty acids to prostaglandins and leukotrienes are the mainstays of treatment in rheumatology. Yet these drugs have little or no action in scleroderma or Sjogren's syndrome and under some circumstances may have adverse effects. Patients with scleroderma have been shown to have very high levels of circulating prostaglandins, coupled with depletion of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. Levels of the metabolites of arachidonic acid, 22:4n-6 and 22:5n-6, which have major roles in maintaining normal cell membrane characteristics were exceptionally low in both plasma and red cell membranes. Others have observed that various functions are highly resistant to normal actions of PGs in scleroderma. This raises the possibility that the high rate of PG formation in scleroderma may be beneficial, in compensation, and that clinical symptoms develop when PG precursors begin to be depleted. Red cell membrane fatty acids patterns in Sjogren's syndrome are almost identical to those in scleroderma. Placebo-controlled trials of supplementation with essential fatty acids have been found to be beneficial in both scleroderma and Sjogren's syndrome.

Animals↗
PubMed1984

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↗