Biomedical subjects

B O Christophersen

Publications and source records attributed to B O Christophersen.

At least 37 records · Page 2Linked to original sources

PubMed1991

Peroxisomal retroconversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) studied in isolated rat liver cells.

Retroconversion of docosahexaenoic acid (DHA, 22:6(n-3)) to eicosapentaenoic acid (EPA, 20:5(n-3)) was studied in isolated rat liver cells. 20% of the substrate was retroconverted to EPA in control cells by one cycle of beta-oxidation probably with delta 4 enoyl CoA reductase and delta 3, delta 2 enoyl CoA isomerase as auxiliary enzymes. This conversion was not stimulated by (-)-carnitine and was not inhibited by the addition of (+)-decanoylcarnitine. In hepatocytes from fasted rats little EPA was formed from DHA. These results strongly suggest that the retroconversion of DHA to EPA is a peroxisomal function. Retroconverted EPA, produced from DHA was rapidly incorporated in triacylglycerol, the phosphatidylcholine and phosphatidyletanolamine fractions. During longer incubation time EPA was partly removed from the phospholipid fractions, chain-elongated to 22:5(n-3) and incorporated in the triacylglycerol fraction.

Animals↗

PubMed1991

Dietary n-6 fatty acids inhibit the incorporation of dietary n-3 fatty acids in thrombocyte and serum phospholipids in humans: a controlled dietetic study.

The effect of a high dietary intake of n-6 fatty acids (36 g daily) vs a low intake (4-6 g daily) on the incorporation of fatty acids from a dietary supplementation of n-3 fatty acids (6 g daily) was studied for 8 weeks in 15 healthy, normolipaemic volunteers. The importance of a high (43.6) vs a low (20.6) energy percentage from fat was also investigated in the participants on a low n-6 intake. Fatty acid analyses of serum and thrombocyte phospholipids showed a marked increase in docosahexaenoic acid (22:6 (n-3), DHA) and especially eicosapentaenoic acid (20:5 (n-3), EPA) in both the high and low n-6 groups after 14 days, but the changes were significantly greater in the low n-6 diet groups. Changes of the ratio between EPA and arachidonic acid (20:4 (n-6), AA) in phospholipids followed an identical pattern in serum and thrombocytes. This indicates that thrombocytes are influenced by the fatty acid composition in serum. The results showed that incorporation of n-3 fatty acids in phospholipids was reduced by a high intake of dietary n-6 fatty acids in the cells and lipid fractions studied. The observed effect of dietary n-6 fatty acids was independent of the energy percentage provided by dietary fat. In order to obtain an optimal effect of n-3 supplementation, the intake of linoleic acid has to be considered and kept at a low level. The serum content of cholesterol was unaffected, but the concentration of triacylglycerol was reduced during the supplementation period.

Adult↗

PubMed1991

The decrease in osmotic fragility of erythrocytes during supplementation with n-3 fatty acids is a transient phenomenon.

In order to study the effect of dietary n-3 fatty acids on osmotic fragility of human erythrocytes, 11 healthy subjects were given a supplement of 6 g day-1 of an oil containing 50% n-3 fatty acids for either 14 days or 34 days. Fourteen days after start the osmotic fragility was decreased by 60-80% (buffer-salt concentration 0.41%), and the level of n-3 fatty acids in membrane phospholipids was increased by approximately 60%. The decrease in fragility was less marked after 24 days and almost at the pre-supplementation level after 34 days. There was no correlation between changes in fragility and in the fatty acid pattern of membrane phospholipids of the erythrocytes. The changes induced in fatty acid composition of phospholipids did not affect membrane fluidity. It is concluded that factors other than the nature of fatty acids in membranes may be involved in modifying osmotic fragility, and that there is no correlation between membrane fragility and membrane fluidity.

Adult↗

PubMed1990

The Zellweger syndrome: deficient conversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) and normal delta 4-desaturase activity in cultured skin fibroblasts.

The metabolism of docosahexaenoic acid (22:6(n-3)) and adrenic acid (22:4(n-6)) was studied in cultured fibroblasts from patients with the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. It was shown that [4,5- 3H]22:6(n-3) is retroconverted to labelled eicosapentaenoic acid (20:5(n-3)) in normal and X-ALD fibroblasts, while this conversion is deficient in Zellweger fibroblasts. [U- 14C]Eicosapentaenoic acid (20:5(n-3)) is elongated to docosapentaenoic acid (22:5(n-3)) in all three cell lines. With [U- 14C]20:5(n-3) as the substrate, shorter fatty acids were not detected. With [4,5- 3H]22:6(n-3) as the substrate, labelled fatty acids were esterified in the phospholipid- and triacylglycerol-fraction to approximately the same extent in all three cell lines. [2- 14C]Adrenic acid (22:4(n-6)) was desaturated to 22:5(n-6) and elongated to 24:4(n-6) in all three cell lines and to the largest extent in the Zellweger fibroblasts. This agrees with the view that the delta 4-desaturase is not a peroxisomal enzyme. The observation that the retroconversion of 22:6(n-3) to 20:5(n-3) is deficient in Zellweger fibroblasts strongly suggest that the beta-oxidation step in the retroconversion is a peroxisomal function. Peroxisomal very-long-chain (lignoceroyl) CoA ligase is probably not required for the activation of 22:6(n-3), since the retroconversion to 20:5(n-3) is normal in X-ALD fibroblasts.

Adrenoleukodystrophy↗

PubMed1989

Beta-oxidation of medium chain (C8-C14) fatty acids studied in isolated liver cells.

The beta-oxidation and esterification of medium-chain fatty acids were studied in hepatocytes from fasted, fed and fructose-refed rats. The beta-oxidation of lauric acid (12:0) was less inhibited by fructose refeeding and by (+)-decanoyl-carnitine than the oxidation of oleic acid was, suggesting a peroxisomal beta-oxidation of lauric acid. Little lauric acid was esterified in triacylglycerol fraction, except at high substrate concentrations or in the fructose-refed state. With [1-14C]myristic acid (14:0), [1-14C]lauric acid (12:0), [1-14C]octanoic acid (8:0) and [2-14C]adrenic acid (22:4(n - 6] as substrate for hepatocytes from carbohydrate-refed rats, a large fraction of the 14C-labelled esterified fatty acids consisted of newly synthesized palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) while intact [1-14C]oleic acid substrate was esterified directly. With [9,10-3H]myristic acid as the substrate, small amounts of shortened 3H-labelled beta-oxidation intermediates were found. With [U-14C]palmitic acid, no shortened fatty acids were detected. It was concluded that when the mitochondrial fatty acid oxidation is down-regulated such as in the carbohydrate-refed state, medium-chain fatty acids can partly be retailored to long-chain fatty acids by peroxisomal beta-oxidation followed by synthesis of C16 and C16 fatty acids which can then stored as triacylglycerol.

Animals↗

PubMed1989

Adrenoleukodystrophy. The chain shortening of erucic acid (22:1(n-9)) and adrenic acid (22:4(n-6)) is deficient in neonatal adrenoleukodystrophy and normal in X-linked adrenoleukodistrophy skin fibroblasts.

The metabolism of long chain unsaturated fatty acids was studied in cultured fibroblasts from patients with X-linked adrenoleukodystrophy (ALD) and with neonatal ALD. By using [14-14C] erucic acid (22:1(n-9)) as substrate it was shown that the peroxisomal beta-oxidation, measured as chain shortening, was impaired in cells from patients with neonatal ALD. The beta-oxidation of adrenic acid (22:4(n-6)), measured as acid-soluble products, was also reduced in the neonatal ALD cells. The peroxisomal beta-oxidation of [14-14C]erucic acid (22:1(n-9)) and [2-14C]adrenic acid (22:4(n-6)) was normal in cells from X-ALD patients. The beta-oxidation, esterification and chain elongation of [1-14C]arachidonic acid (20:4(n-6)) and [1-14C]eicosapentaenoic acid (20:5(n-3)) was normal in both X-linked ALD and in neonatal ALD. Previous studies suggest that the activation of very long chain fatty acids by a lignoceryl (24:0)-CoA ligase is deficient in X-linked ALD, while the peroxisomal beta-oxidation enzymes are deficient in neonatal ALD. The present results suggest that the peroxisomal very long-chain acyl-CoA ligase is not required for activation of unsaturated C20 and C22 fatty acids and that these fatty acids can be efficiently activated by the long chain acyl-(palmityl)-CoA ligase.

Adrenoleukodystrophy↗

PubMed1988

The Zellweger syndrome: deficient chain-shortening of erucic acid (22:1 (n-9)) and adrenic acid (22:4 (n-6)) in cultured skin fibroblasts.

In the Zellweger syndrome where peroxisomes are absent, extremely long fatty acids (24:0 and 26:0) accumulate in tissues suggesting that these fatty acids are normally beta-oxidized in the peroxisomes. Previous studies with rat hepatocytes suggest that peroxisomes are also important in oxidation of C22 unsaturated fatty acids. This study shows that cultured fibroblasts from normal human controls shorten [14-14C]erucic acid (22:1(n-9)) to oleic acid (18:1(n-9)) efficiently while Zellweger fibroblasts are deficient in chain-shortening. [2-14C]Adrenic acid (22:4(n-6)) is oxidized in control fibroblasts probably by chain-shortening to arachidonic acid (20:4(n-6)). Only a little adrenic acid is oxidized in Zellweger fibroblasts. Linolenic acid (18:3(n-3)) is desaturated and chain-elongated in both control and Zellweger fibroblasts. The results support the view that peroxisomes play a normal physiological role in the shortening of C22 unsaturated fatty acids and that this function is deficient in Zellweger fibroblasts.

Cells, Cultured↗

PubMed1988

Mechanisms for the serum lipid-lowering effect of n-3 fatty acids.

Both epidemiological and experimental studies have demonstrated that a high content of n-3 fatty acids in the diet lowers serum lipid concentration. However, the mechanism for this effect is unclear. In this present study it has been shown that labelled linolenic acid (18:3, n-3) is oxidized to a larger extent than linoleic acid (18:2,n-6) in isolated rat hepatocytes. Conversely, the incorporation of linolenic acid and the desaturated/chain-elongated products in VLDL-triacylglycerol is decreased compared with linoleic acid. Dietary n-3 fatty acids have probably a depressing effect on both hepatic triacylglycerol synthesis and on secretion of VLDL. The finding that n-3 fatty acids are transported from the liver as ketone bodies to a larger extent than n-6 fatty acids may thus explain that a high intake of n-3 fatty acids is not accompanied with hepatic steatosis.

Animals↗

PubMed1988

Regulation of the metabolism of polyunsaturated fatty acids.

The object of the present work has been to assess some aspects of the control of the metabolism of polyunsaturated fatty acids. In these studies we have used isolated cells; hepatocytes and cardiac myocytes from rat, and lymphocytes and fibroblasts from humans. Attention has focused on the importance of dietary and hormonal factors which can exert an effect shortly after activation of fatty acid, and thus may determine whether the fatty acid will be desaturated, chain-elongated, directly esterified or oxidized. Both the short-term and long-term regulation excerted by dietary fat have been studied in both rat and human. Profound sex-differences exist in fatty acid esterification, oxidation and fatty acid composition in lipoproteins. It is suggested that these differences, at least in part are due to a different content of intracellular fatty acid binding proteins in female and male liver. The peroxisomal retroconversion of C22-unsaturated fatty acids to their C20-homologues is probably involved in the regulation of fatty acid composition in membrane phospholipids, being a sort of "overflow valve". In several somewhat different diseases the patients have no peroxisomes or their peroxisomes are defective. In these peroxisomal diseases the beta-oxidation of very long-chain fatty acids is deficient. In this present work we show that fibroblast from patients with the peroxisomal diseases, Zellweger disease, X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy differ in their ability to shorten C22-fatty acids.

Animals↗

PubMed1987

Sex-related differences in desaturation and chain elongation of essential fatty acids studied in isolated rat hepatocytes.

When [14C]linoleic acid (18:2(n-6)) or [14C]dihomogammalinolenic acid (20:3(n-6)) was incubated with isolated liver cells from rats fed an essential fatty acid deficient diet, delta 6- and delta 5-desaturation, chain elongation and synthesis of 14C-labelled C14-C18 fatty acids (from [14C]acetate) were enhanced in female cells compared with male ones. No sex difference in total secretion of very low density lipoproteins (VLDL) was observed. However, VLDL secreted from female cells contained significantly more C16-C18 fatty acids than male cells. It is suggested that the observed sex differences, at least in part, may be related to the different content of fatty acid binding proteins in female cells compared with males.

8,11,14-Eicosatrienoic Acid↗

PubMed1987

In vitro effects of alpha-bromopalmitate on metabolism of essential fatty acids studied in isolated rat hepatocytes: sex differences.

alpha-Bromopalmitate was shown to have a far more pronounced effect on metabolism of labelled linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) in isolated liver cells from female rats than in those from males. alpha-Bromopalmitate decreased triacylglycerol synthesis with a concomitant accumulation of fatty acid in diacylglycerol, indicating that the acylation of diacylglycerol is affected by alpha-bromopalmitate.

Animals↗

PubMed1986

Mitochondrial and peroxisomal oxidation of arachidonic and eicosapentaenoic acid studied in isolated liver cells.

The partitioning between peroxisomal and mitochondrial beta-oxidation of [1-14C]eicosapentaenoic acid (20:5(n-3] and [1-14C]arachidonic acid (20:4(n-6)) was studied. In hepatocytes from fasted rats approximately 70% of the fatty acid substrate was oxidized with oleic, linoleic, eicosapentaenoic and docosahexaenoic (22:6(n-3)) acid, even more with adrenic (22:4(n-6)) and less with arachidonic acid. When the mitochondrial oxidation was suppressed by fructose refeeding and by (+)-decanoylcarnitine, the fatty acid oxidation in per cent of that in cells from fasted rats was with 18:1(n-9) 7%, 18:2(n-6) 8%, 20:4(n-6) 12%, 20:5(n-3) 20%, 22:4(n-6) 57% and for 22:6(n-3) 29%. The fraction of 14C recovered in palmitate and other newly synthesized fatty acids after fructose refeeding decreased in the order 22:4(n-6) greater than 22:6(n-3) greater than 20:5(n-3) greater than 20:4(n-6) and was very small with 18:1(n-9) and 18:2(n-6). In cells from both fed and fructose-refed animals 20:5(n-3) was efficiently elongated to 22:5(n-3) and 22:6(n-3). 20:5(n-3) and 20:4(n-6) were not elongated after fasting. The phospholipid incorporation with [1-14C]20:5(n-3) decreased during prolonged incubations while it remained stable with [1-14C]arachidonic acid. The results suggest that peroxisomes contribute more to the oxidation of 20:5(n-3) than with 20:4(n-6) although both substrates are probably oxidized mainly in the mitochondria.

Animals↗

PubMed1986

Sex differences in the metabolism of essential fatty acids studied in isolated rat liver cells.

The triacylglycerol synthesis from exogenous linoleic acid (18:2(n-6], linolenic acid (18:3(n-3], dihomogammalinolenic acid (20:3(n-6], eicosapentaenoic acid (20:5(n-3] and oleic acid (18:1(n-9] was observed to be significantly increased in isolated liver cells from female rats compared with males. The rate of fatty acid oxidation and phospholipid biosynthesis was concomitantly more important in male cells. With the C22-polyenoic fatty acids, adrenic acid (22:4(n-6] and docosahexaenoic acid (22:6(n-3), only a minor sex-related difference in fatty acid metabolism was found.

Animals↗

PubMed1986

Evidence for peroxisomal retroconversion of adrenic acid (22:4(n-6)) and docosahexaenoic acids (22:6(n-3)) in isolated liver cells.

The intracellular localization of the oxidation of [2-14C]adrenic acid (22:4(n-6)) and [1-14C]docosahexaenoic acid (22:6(n-3)) was studied in isolated liver cells. The oxidation of 22:4(n-6) was 2-3-times more rapid than the oxidation of 22:6(n-3), [1-14C]arachidonic acid (20:4(n-6)) or [1-14C]oleic acid (18:1). (+)-Decanoylcarnitine and lactate, both known to inhibit mitochondrial beta-oxidation, reduced the oxidation of 18:1 distinctly more efficiently than with 22:4(n-6) and 22:6(n-3). In liver cells from rats fed a diet containing partially hydrogenated fish oil, the oxidation of 22:6(n-6) and 22:6(n-3) was increased by 30-40% compared with cells from rats fed a standard pellet diet. With 18:1 as substrate, the amount of fatty acid oxidized was very similar in cells from animals fed standard pellets or partially hydrogenated fish oil. Shortened fatty acids were not produced from [5,6,8,9,11,12,14,15-3H]arachidonic acid. In hepatocytes from rats starved and refed 20% fructose, a large fraction of 14C from 22:4 was recovered in 14C-labelled C14-C18 fatty acids. Oxidation of 22:4 thus caused a high specific activity of the extramitochondrial pool of acetyl-CoA. The results suggest that 22:4(n-6) and to some extent 22:6(n-3) are oxidized by peroxisomal beta-oxidation and by this are retroconverted to arachidonic acid and eicosapentaenoic acid.

Animals↗

PubMed1986

Desaturation and chain elongation of essential fatty acids in isolated liver cells from rat and rainbow trout.

Isolated hepatocytes from rainbow trout and rat were incubated with 14C-labeled linoleic acid, linolenic acid, dihomogammalinolenic acid or eicosapentaenoic acid. The most striking difference in the desaturase activity was the lower level of delta 5 desaturase in trout than in rat. No delta 4 desaturation of 22:4(n-6) to 22:5(n-6) was observed in either of the two species, while the conversion of 22:5(n-3) to 22:6(n-3) was significant in both groups and highest in rainbow trout. The chain-elongating activity was remarkably similar in the two species, except for the "dead-end" elongation which was distinctly more important in fish.

Animals↗

PubMed1986

Eicosapentaenoic- and arachidonic acid metabolism in isolated liver cells.

The oxidation and esterification of 14C labelled eicosapentaenoic acid (20:5,n-3) and arachidonic acid (20:4,n-6) in isolated liver cells has been studied. The bioconversion of C18 and C22 polyunsaturated fatty acids to 20:5(n-3) and 20:4(n-6) is also discussed. Adrenic acid (22:4,n-6) and docosahexaenoic acid (22:6,n-3) are retroconverted to 20:4(n-6) and 20:5(n-3) respectively by peroxisomal beta-oxidation. 20:4(n-6) and 20:5(n-3) are both mainly oxidized in the mitochondria. The peroxisomal contribution to the oxidation of 20:5,n-3 is however larger than with 18:2(n-6) and 18:1(n-9) which are predominantly oxidized by mitochondrial beta-oxidation. Isolated liver cells oxidize more 20:5(n-3) and esterify less than observed with 20:4(n-6) as substrate. In liver cells from essential fatty acid deficient animals 20:5(n-3) and 20:4(n-6) are both efficiently directed to the phospholipids. In hepatocytes from animals fed a diet rich in 18:2(n-6) and 18:3(n-3) arachidonic acid is still to a large extent esterified in the phospholipids while 20:5(n-3) only to a small extent is esterified in this lipid fraction. 18:2(n-6) is much more efficiently esterified in the phospholipids than is 18:3(n-3) which is also rapidly removed from the phospholipids. The delta 4 desaturase activity is increased in essential fatty acid deficiency similar to delta 6 desaturase. The competition between 18:3(n-3) and 18:2(n-6) for delta 6 desaturation in combination with a much higher dietary intake of 18:2(n-6) than of 18:3(n-3) may limit the conversion of dietary 18:3(n-3) to 20:5(n-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Norflurazon--an inhibitor of essential fatty acid desaturation in isolated liver cells.

Norflurazon is a herbicide known to inhibit carotene biosynthesis and linolenic acid biosynthesis in plants. In the present work, the effect of norflurazon on the metabolism of studied in isolated rat liver cells and in rat liver microsomes, incubated with [1-14C] labeled linolenic acid (18:3, n-3), dihomogammalinolenic acid (20:3, n-6) and eicosapentaenoic acid (20:5, n-3). Norflurazon (0.1 mM, 1.0 mM) was found to inhibit essential fatty acid desaturation. The delta 6 desaturation is inhibited more efficiently than the delta 5 and delta 4 desaturation. The chain elongation of essential C18 fatty acids to their C20 and C22 homologs was not inhibited by norflurazon.

Animals↗

PubMed1984

Effect of dietary fats on arachidonic acid and eicosapentaenoic acid biosynthesis and conversion to C22 fatty acids in isolated rat liver cells.

The desaturation, chain elongation and esterification of [1-14C]eicosapentaenoic acid, [1-14C]arachidonic acid, [1-14C]eicosatrienoic acid, [1-14C]linolenic acid and [1-14C]linoleic acid were studied in isolated liver cells. Rats fed diets with either 15% hydrogenated coconut oil or 15% partially hydrogenated marine oil, both deficient in essential fatty acids, 15% soybean oil or standard pellet diet with 6% fat, were used. The delta 4-desaturation of 22:5(n - 3) and 22:4(n - 6) as well as the delta 6-desaturase activity was distinctly higher in cells from animals fed coconut or marine oil than with soybean oil or standard pellet. The rate of delta 5-desaturation of 20:3(n - 6) and 20:4(n - 3) was nearly the same in cells from rats fed coconut, marine and soybean oils and higher than with standard pellet. The chain elongation of 20:5(n - 3) to 22:5(n - 3) was distinctly more pronounced than the elongation of 20:4(n - 6) with all four diets. 20:5(n - 3) was mainly esterified in the phospholipids with marine and coconut oils, and mainly in triacylglycerol with standard pellet and soybean oils. The proportion of [1-14C]20:4(n - 6) in the phospholipids to that in triacylglycerol decreased in the order marine oil greater than coconut oil greater than standard pellet greater than soybean oil. The different endogenous arachidonic acid content in the phospholipids induced by the different diets increased in the same order. 20:5(n - 3) was rapidly esterified in triacylglycerol and phospholipids, then liberated especially from the triacylglycerol fraction, chain elongated to 22:5(n - 3) and reesterified.

Animals↗