Biomedical subjects

M Narce

Publications and source records attributed to M Narce.

At least 37 records · Page 2Linked to original sources

PubMed1994

Age-related changes in linoleic acid bioconversion by isolated hepatocytes from spontaneously hypertensive and normotensive rats.

This study points out the hepatocyte interconversion of the linoleic acid family during hypertension. Hepatocyte delta 6 desaturase activity was higher in 1 month-old spontaneously hypertensive rats than in normotensive controls. A similar tendency was observed in 6 month-old SHR. delta 5 desaturase activity was higher only in 1 month-old spontaneously hypertensive rats as compared to controls. Desaturase activities were particularly high at the age of 6 months. The hepatocyte fatty acid composition showed an impairment of n-6 polyunsaturated fatty acid metabolism in spontaneously hypertensive animals. Changes were greater in the young prehypertensive rats than in adults. A storage of n-3 long chain fatty acids is remarkable in adult hypertensive rats, suggesting an alteration in peroxisomal oxidation. Such modifications may be related to the prostaglandin precursors availability to peripheral tissues such as kidney.

Aging↗

PubMed1994

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats.

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.

Aging↗

PubMed1994

Adrenic acid delta 4 desaturation and fatty acid composition in liver microsomes of spontaneously diabetic Wistar BB rats.

We examined the delta 4 (n-6) desaturation and the fatty acid composition of liver microsomes in the insulin-dependent spontaneously diabetic Wistar Bio-Breeding (BB) rat. The desaturation of adrenic acid to n-6 docosapentaenoic acid was decreased in the normo- and hyperglycemic diabetic rats. Insulin treatment with 1.0 IU. 100 g body weight-1 twice a day for 2 days restored the reduced activity during the hypoglycemic period. The pattern of responses was similar to that of linoleic acid delta 6 and dihomo-gamma-linolenic acid delta 5 desaturases, with a non-parallel relationship between the desaturation system and the glycemia. The microsomal fatty acid composition of BB rat liver reflected only partially to the delta 4 desaturation at different states of glycemia. Factors other than impaired desaturation system are involved in the fatty acid metabolism of spontaneously diabetic rats.

Animals↗

PubMed1994

Psychosocial stress, catecholamines, and essential fatty acid metabolism in rats.

To examine the effects of psychosocial stress and the "stress hormone," epinephrine, on essential fatty acid metabolism in rats, two studies were conducted. In the first, the effects of four weeks of (i) social isolation and (ii) group housing (control) on liver microsomal delta 6 and delta 5 n-6 desaturase activity were studied in group-reared male normotensive (Wistar Kyoto) and spontaneously hypertensive (SHR) rats (n = 5/group). The second study examined the effects of acute ip epinephrine (0.0, 1.0, 2.0, and 4.0 mg/kg) 6 hr prior to and following an ig dose (4 g/kg) of safflower oil (rich in 18:2n-6, LA) on plasma and liver LA, 20:4n-6 (AA), and LA/AA ratios in adult essential fatty acid deficient Sprague-Dawley rats (n = 6/group). In the first experiment, isolation stress significantly inhibited the activity of delta 6 (P < 0.05) and delta 5 (P < 0.01) desaturase in the normotensive rats and of delta 5 desaturase in the SHR (P < 0.05). In the second study, epinephrine increased plasma and liver LA at doses 1.0 and 2.0 mg/kg in most of the fractions examined, and suppressed AA levels. The response of the LA/AA ratio to epinephrine varied between tissues and among lipid fractions, but increased this ratio at the moderate doses (2.0-4.0 mg/kg) of epinephrine in most cases. These data suggest that psychosocial stressors are capable of inhibiting the rate limiting steps of essential fatty acid metabolism and that this response is more pronounced in the SHR than in the Wistar Kyoto. They also suggest that epinephrine is capable of altering the in vivo metabolism of essential fatty acids in the rat.

Analysis of Variance↗

PubMed1993

Evidence that liver microsomes of human neonates desaturate essential fatty acids.

delta 6- and delta 5-Desaturation of essential fatty acids of n-6 and n-3 series are required for the biosynthesis of polyunsaturated fatty acids (PUFAs), which are precursors of eicosanoids and constituents of membrane phospholipids. This pathway could be of special importance during the perinatal period, when PUFAs accretion in the central nervous system is very active. However, experimental evidence of delta 6- and delta 5-desaturase activities in man is very scarce, and no data are available for newborns. We report the delta 6- and delta 5-desaturase activities detected in human liver microsomes from three neonates who died from associated malformations. Radiochemical assays of delta 6- and delta 5-desaturase activities performed with reverse phase HPLC analysis of the products in the n-6 series ranged from 4.8-13.6 to 3.2-16.4 pmol substrate converted.min-1.mg-1 microsomal proteins, respectively. In the n-3 series delta 6-desaturase activity ranged from 5.3 to 12.8 pmol.min-1.mg-1. The relationships between enzyme activities and substrate concentrations suggest excess substrate inhibition for n-6 and not for n-3 fatty acids. These results demonstrate significant delta 6- and delta 5-desaturase activities in human liver of neonates, but this activity was lower than previously reported in adult humans and in mammals, especially rodents.

Delta-5 Fatty Acid Desaturase↗

PubMed1993

Effect of salt-loading and spontaneous hypertension on in vitro metabolism of [1-14C]linoleic and [2-14C]dihomo-gamma-linolenic acids.

The present study compared the effect of spontaneous hypertension and salt-loading on in vitro metabolism of 18:2n-6 (linoleic acid) and 20:3n-6 (dihomo-gamma-linolenic acid). Ten weanling spontaneously hypertensive rats (SHR) and 10 normotensive Wistar-Kyoto rats (WKY) maintained on a rodent lab chow were given tap water with (n = 5) or without (n = 5) addition of 1% NaCl for 4 weeks. Thereafter, animals were killed and liver microsomes were prepared. Aliquots of microsomes suspended in the phosphate-sucrose buffer containing MgCl2, ATP, CoA, and NADPH were incubated with 0.3 microCi of [1-14C]-18:2n-6 or [2-14C]-20:3n-6 at 37 degrees C for 15 min. The activity of delta 6- and delta 5-desaturases, and the distribution of radioactivity in different lipid fractions and in phospholipid fatty acids were determined. Results showed that both spontaneous hypertension and salt-loading suppressed the desaturation of radiolabeled 18:2n-6 and of 20:3n-6. Incubation of microsomes with [1-14C]-18:2n-6 resulted in 29% of radioactivity being associated with phospholipid fraction, of which 3% was associated with 18:3n-6. Incubation with radiolabeled 20:3n-6 resulted in 30% of the radioactivity being incorporated into phospholipids, of which 50% was associated with 20:4n-6 (arachidonic acid). Salt-loading suppressed the incorporation of radiolabeled fatty acids into phospholipids, more so in SHR than in WKY. Thus, salt-loading not only suppressed the desaturation of 18:2n-6 and 20:3n-6, but also interfered with the acylation of n-6 fatty acids into the phospholipid fraction.

Animals↗

PubMed1992

Evidence for insulin dependent hepatic microsomal gamma-linolenic acid chain elongation in spontaneously diabetic Wistar BB rats.

We studied hepatic microsomal gamma-linolenoyl-CoA elongation and fatty acid composition of liver microsomes in spontaneously diabetic Wistar BB rats. The liver microsomal gamma-linolenoyl-CoA elongation was decreased in diabetic Wistar BB rats during both normo- and hyperglycemic periods and restored during the hypoglycemic period following insulin treatment. These results are in agreement with our previously reported data on linoleic acid delta 6 and delta 5 desaturations and support the non-parallel relationship between the chain elongation system and the glycemia. The fatty acid composition of BB rat liver microsomes was only partially consistent with the gamma-linolenoyl-CoA elongation activity at the different periods of glycemia, probably because factors other than elongation impairments were involved in the evolution of fatty acid composition.

Acyl Coenzyme A↗

PubMed1992

Effect of sodium loading (3% NaCl) on arachidonic acid biosynthesis in rat liver microsomes.

Sodium loading increases arachidonic acid (AA) metabolism by way of the prostaglandins(PGs) from series 2. Its effect on AA biosynthesis remains unknown. The purpose of the present study was to investigate the influence of sodium loading on the fatty acid composition of liver and liver microsomes, and the liver microsomal delta-6 and delta-5 desaturations of linoleic acid (LA) into AA. We found a decrease of LA and dihomo-gamma-linolenic acid (DGLA) levels in liver total lipids of Wistar rats receiving hypernatriuretic drinking water (NaCl 3%) for 60 days. At the same time AA increased. DGLA decreased and AA increased in liver microsomal total lipids. 1(14) C-LA delta-6 desaturase and 2(14) C-DGLA delta-5 desaturase activities increased in liver microsomes. These results show that, in addition to its influence on the regulation of glomerular filtration, sodium loading is involved in the regulation of liver AA biosynthesis.

Animals↗

PubMed1992

Depletion of delta 9 desaturase (EC 1.14.99.5) enzyme activity in growing rat during dietary protein restriction.

The effects of protein restriction on delta 9 desaturase (EC 1.14.99.5) activity were studied in growing rats. A control group was fed on a balanced diet (200 g casein/kg; BD) for 28 d. The experimental group was fed on the low-protein diet (20 g casein/kg; LP) for 26 d, then refed the balanced diet (BD-R) for 2 d. Rats were born to and suckled from normally fed dams. The enzyme activity was measured after 2 and 14 d of LP, and 26 d of LP plus 2 d of BD-R, by incubations in vitro of hepatic microsomal pellets with [1-14C]steric acid. The results indicated a decreased delta 9 desaturase activity after 2 and 14 d of LP of -33 and -43% respectively. Refeeding for 2 d was sufficient to super-repair this activity (+66%). The fatty acid composition of total liver lipids and microsomal phosphatidylethanolamines (PE) and phosphatidylcholines (PC) were also investigated; 18:0 decreased in total liver lipids at 14 d of LP, when 18:1n-9 increased. Stearic acid (18:0) increased in PC at 2 d of LP and in PE at 14 d of LP; oleic acid (18:1n-9) did not change. Therefore, it is concluded that a defect occurred in the bioconversion of 18:0 into 18:1n-9 by delta 9 desaturation during protein depletion. As oleic acid is accumulated in total liver lipids during LP, we speculate that this is due to a decreased oxidation or transport of this fatty acid.

Animals↗

PubMed1989

The effects of alkylthioacetic acids (3-thia fatty acids) on fatty acid metabolism in isolated hepatocytes.

Long-chain alkylthioacetic acids (3-thia fatty acids) inhibit fatty acid synthesis from [1-14C]acetate in isolated hepatocytes, while fatty acid oxidation is nearly unaffected or even stimulated. Desaturation of [1-14C]stearate (delta 9-desaturase) is also unaffected. [1-14C]Dodecylthioacetic acid (a 3-thia fatty acid) is incorporated in triacylglycerol and in phospholipids more efficiently than [1-14C]palmitate in isolated hepatocytes. The metabolism of [1-14C]dodecylthioacetic acid to acid-soluble products (by omega-oxidation) is slow compared to the oxidation of [1-14C]palmitate. In hepatocytes from adapted rats (rats fed tetradecylthioacetic acid for 4 days) the rate of [1-14C]palmitate oxidation is increased and its rate of esterification is decreased. Stearate desaturation is also decreased. The rate of cyanide-insensitive peroxisomal fatty acid beta-oxidation is several-fold increased. The metabolic effects of long-chain 3-thia fatty acids are discussed and it is concluded that they behave essentially like normal fatty acids except for their slow breakdown due to the sulfur atom in the 3 position, which blocks normal beta-oxidation.

Acetates↗

PubMed1989

The effect of dietary alpha-bromopalmitate on blood lipids in the rat.

When alpha-bromopalmitate was fed to rats for 9-30 days, the level of serum triacylglycerol increased up to 2-fold over the concentration of controls. alpha-Bromopalmitate treatment had no effect on concentration of complex lipids in liver, while the triacylglycerol level in heart was significantly enhanced. From metabolic studies using isolated hepatocytes and liver microsomes, it is suggested that the increased serum triacylglycerol level after alpha-bromopalmitate feeding is mainly due to reduced fatty acid oxidation in both liver and peripheral tissues, and to a lesser extent, to inhibited fatty acid uptake and esterification.

Animals↗

PubMed1989

Liver microsomal delta 6 and delta 5 linoleic acid desaturation in female BB rats.

Rat liver microsomal delta 6 and delta 5 desaturation are defective in experimental diabetes, but this defect is correctable with insulin treatment. Rat liver fatty acid composition and delta 6 and delta 5 desaturation were studied in the spontaneously diabetic adult female Bio-Breeding (BB) rat. Control Wistar rats and BB rats (4 weeks of diabetes), that received insulin (1 IU.100 g body weight-1.day-1), were killed 20 h after the last insulin injection. delta 6 and delta 5 desaturase activities were estimated from the incubation of liver microsomes with (1-14C) 18:2, n-6 or (2-14C) 20:3, n-6, respectively, and the fatty acid composition of the liver and microsomal liver lipids were investigated. Under experimental conditions delta 6 and delta 5 desaturase activities were unchanged in the BB rats when compared to the control rats. Impairment of the liver fatty acid composition of diabetic BB rats is not consistent with normal desaturase activity and may be explained by factors other than desaturation disturbance.

Animals↗

PubMed1988

Method for evaluating the bioconversion of radioactive polyunsaturated fatty acids by use of reversed-phase liquid chromatography.

Reversed-phase high-performance liquid chromatography on a thermostatted octadecylsilyl column was used to separate mixtures of labelled polyunsaturated fatty acids (as their methyl esters) formed by successive desaturations and elongations of labelled linoleic (18:2 n - 6) or linolenic (18:3 n - 3) acid by rat liver microsomes. Acetonitrile-water mixtures were used for elution of the esters. Unsaturated and saturated esters were detected by their refractive indices. The order of elution of fatty acid methyl esters in complex mixtures varies as a function of the chain length and unsaturation, analysis temperature, water concentration and solvent flow-rate. The peak areas vary as a function of the unsaturation. Specific radioactivities of 14C-labelled fatty acids and the percentage distribution of radioactivity among fatty acids from complex mixtures can be efficiently determined by collection and direct measurement of the radioactivity in the solvent by liquid scintillation counting. The method can be applied to complete compositional analysis, but is especially useful for determination of specific radioactivities during studies on the metabolic conversion of labelled polyunsaturated fatty acids.

Chromatography, Gas↗

PubMed1988

Time-course effects of protein malnutrition on hepatic fatty acids delta 6 and delta 5 desaturation in the growing rat.

1. In growing rats, the time-course effects of giving a normal-protein diet (200 g casein/kg; NP) for 52 d, a low-protein diet (20 g casein/kg; LP) for 52 d and a LP diet for 26 d followed by balanced refeeding (200 g casein/kg; BR) for 26 d, on the fatty acid composition of liver total lipids and microsomal phospholipids were investigated together with delta 6- and delta 5-microsomal desaturase activities. 2. The oleic acid content (mg/g tissue) of liver total lipids increased progressively with the LP diet, while linoleic acid was increased only at days 7 and 52. 20:3 omega 6, 20:4 omega 6, 22:5 omega 6 and 22:6 omega 3 fatty acids decreased during the period on the LP diet. BR for 7 d was sufficient to restore the fatty acid composition of total lipids to control values. Changes in the fatty acid composition of liver microsomal L-alpha-phosphatidylcholines were observed only after 52 d on the LP diet; the proportions (% w/w total fatty acids) of 18:0, 20:3 omega 6 and 20:4 omega 6 fatty acids decreased while oleic acid increased. The fatty acid composition of L-alpha-phosphatidylethanolamines was less affected. 3. delta 6- and delta 5-desaturase activities decreased to 20-30% of their original values after 2 d on the LP diet; a smaller deficit prevailed after 14 d but disappeared after 25 d, to appear again after 52 d. As early as day 2 of BR, desaturase activities were greatly recovered and returned to control values at day 13. 4. The present work shows that modifications in microsomal delta 6- and delta 5-desaturase activities are not strictly paralleled by the changes in the composition of fatty acids of liver total lipids and microsomal phospholipids.

Animals↗

PubMed1988

[Hepatic microsomal delta 9 desaturation of stearic acid in the spontaneously diabetic female BB rat].

delta 9 desaturation of stearic (1-14C) acid has been estimated from incubation of liver microsomes of adult female spontaneously diabetic BB rat, an animal model resembling the spontaneous juvenile diabetes in humans, comparatively to adult female control Wistar rat. The animals were sacrificed, when hyperglycemic, 24 hours after the last insulin injection to the BB rats. Stearic acid delta 9 desaturase activity is drastically depressed in the BB rats when fatty acid composition of liver phospholipids and microsomal total liver lipids are changed in spite of the daily injection of insulin necessary for the BB rats survival.

Animals↗

PubMed1986

[Chronologic studies of the effects of a hypoproteinic diet followed by an equilibrated diet on delta-6 and delta-5 desaturations of linoleic acid in liver microsomes in the rat].

A low protein diet affects amounts of linoleic and arachidonic acids in hepatic microsomal phospholipids of growing rats. Are the changes related to modifications in microsomal delta 6- and delta 5- linoleic acid desaturase activities? Two groups of Wistar rats weighing 80 +/- 5 g at the beginning of the experiment were used: Control group (T) was fed on a 16% gluten + 4% casein diet for 53 days; Experimental group (E) was fed on a 4% gluten + 1% casein diet for 26 days (MP) then Control diet for 27 days (RE). After 2, 14 and 26 days of MP and 2, 15 and 27 days of RE, rats of each group were sacrificed. Protein and water contents of liver, quantitative fatty acid, composition of total lipids in liver and hepatic microsomes were determined. delta 6- and delta 5- linoleic acid desaturase activities were estimated from incubation of liver microsomes with [1-14C] C 18: 2 n-6 or [2(14)C] C 20: 3 n-6 respectively. The low protein diet stops practically ponderal growth. The fatty-acid compositions of microsomal total lipids of E rats were affected in comparison with values of T rats. These modifications persist after 27 days of RE. The C 20: 4 n-6/C 18: 2 n-6 ratio in microsomal total lipids was slightly different between T and E rats but increased strongly during refeeding. Same modifications take place in the fatty-acid composition of hepatic total lipids. After two days of MP, delta 6- and delta 5- desaturase activities were depressed, phenomenon that not persist in the course of MP. These enzyme activities increase to higher values than those of the T after two days of RE.

Animals↗

PubMed1985

[In vitro study of delta-6- and delta-5-desaturation of linoleic and dihomo-gamma-linolenic acids in WKY rats on a high-sodium diet].

Delta 6- and delta 5-desaturation activities of linoleic [1(4)C] and dihomo-gamma-linolenic [2(14)C] acids are increased, in vitro, in liver microsomes of normotensive rats WKY, which receive an hypernatriuric diet (NaCl 3%). These results lead to a best known of delta 6- and delta 5-desaturases, which are involved in fundamental steps of linoleic acid metabolites biosynthesis, implicated in blood pressure regulation.

8,11,14-Eicosatrienoic Acid↗

PubMed1984

[In vitro study of delta 6- and delta 5-desaturations of linoleic and dihomo-gamma-linolenic acids during the development of arterial hypertension as a function of age in spontaneously hypertensive rats (SHR) as compared to normotensive rats (WKY)].

delta 6- and delta 5-desaturations of linoleic [1(14)C] or dihomo-gamma-linolenic [2(14)C] acids are partially inhibited, in vitro, in liver microsomes of spontaneously hypertensive rats (SHR) comparatively to normotensive rats (WKY). The inhibition is more light when the animals are young and the blood hypertension not well established. These results are particularly important, for these desaturations are fundamental steps in the biosynthesis of prostaglandins precursors, prostaglandins and their original fatty acids being involved in blood pressure regulation.

8,11,14-Eicosatrienoic Acid↗