Δ6 and Δ5 desaturase activities in liver from obese zucker rats at different ages

Δ6 Desaturation of linoleic acid (18∶2 n−6) and Δ5 desaturation of dihomo-γ-linolenic acid (20∶3 n−6) were measured in liver microsomes from genetically obese Zucker rats (fa/fa) and from their lean littermates (Fa/−). Both groups were fed a balanced commercial diet. The rats were 6, 9 and 12 weeks old, which corresponded to stages in their active growth period. The content of total fatty acids and n−6 polyunsaturated fatty acids in whole liver and liver microsomes was also determined in order to ascertain how the desaturase activities measuredin vitro reflected regulation of essential fatty acid metabolismin vivo. Contrary to values obtained for Δ6 desaturation, Δ5 desaturation at nonsaturating substrate levels were lower in obese rats than in lean controls. In contrast, at saturating substrate level, the maximal Δ5 desaturase activities were the same in both phenotypes and they increased with age. Study of Δ5 desaturation kinetics (1/V vs 1/S) showed that V_m did not differ between 12-week-old obese and lean rats, whereas K_M in obese rats was much lower than in controls, expressing the very low affinity of the enzyme for the substrate in obese animals. The fatty acid composition of liver lipids reflected the results of desaturase activitiesin vitro. In particular, the ratios 20∶4 n−6/20∶3 n−6 were lower in obese rats than in lean rats, which can be explained by the lower conversion of 20∶3 n−6 into 20∶4 n−6 by Δ5 desaturation. However, the total amount of 20∶4 n−6 in the whole liver did not differ between phenotypes, whatever their age. This work presents evidence for a relationship between the changes in fatty acid compositional data in hepatic total lipids, total lipids of liver microsomes and modifications of fatty acid desaturase activities in the genetically obese Zucker rat.     

Dietary arachidonic acid and hepatic desaturation of fatty acids in obese zucker rats

The effect of low levels of dietary arachidonic acid (20:4n-6) on Δ6 desaturation of linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20:3n-6) were studied in liver microsomes of obese Zucker rats, in comparison with their lean littermates. Fatty acid composition of serum total lipids and of phospholipids from liver microsomes and from total heart and kidney was determined to see whether modifications of desaturation rate, if any, were reflected in the tissue fatty acid profiles. Animals fed for 12 wk on a balanced diet, containing 20:4n-6 and 18:2n-6, were compared to those fed 18:2n-6 only. The low amount of dietary 20:4n-6 greatly inhibited Δ6 desaturation of 18:2n-6 and Δ5 desaturation of 20:3n-6, whereas Δ6 desaturation of 18:3n-3 was slightly increased in obese rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids by dietary arachidonic acid was only slightly reflected in the 20:4n-6 content of liver microsome phospholipids. On the contrary, the enrichment of serum total lipids and heart and kidney phospholipids in this fatty acid was pronounced, more in obese than in lean animals. Our results show that, although the desaturation rate of the n-6 fatty acids in liver microsomes was greatly decreased by the presence of arachidonic acid in the diet, the tissue phospholipid content in arachidonic acid was not depressed. The potentiality of synthesis of eicosanoids of the 2 family from this fatty acid is consequently not lower, especially in obese rats, in which certain tissues are deficient in arachidonic acid, in comparison with their lean littermates.     

Effect of a diet rich in sunflower oil on aspects of lipid metabolism in the genetically-obese rat

Aspects of the lipid metabolism of male, obese and lean Zucker rats were compared using animals which had been fed ad libitum for 32 days on a diet (HS) which contained 200 g sunflowerseed oil/kg or one (LS) which contained 50 g/kg of the oil. When compared with the LS diet, the HS diet decreased the characteristic lipid accretion in the liver of obese rats from 126 mg (LS) to 81 mg (HS)/g wet weight; corresponding values for the lean rats were 39 mg and 56 mg/g wet weight of liver, respectively. The HS diet depressed lipid synthesis de novo by liver homogenates and decreased the Δ9-desaturase activity of liver microsomes from obese and clean rats by about 50%. Δ9-Desaturase activity in vitro was also depressed by the addition of linoleic acid to liver microsomes from both obese and lean rats fed ad libitum on a standard laboratory diet. Depressed Δ9-desaturase activity, due to ingestion of the HS diet, was reflected in lower ratios of 16∶1/16∶0 and 18∶1/18∶0 fatty acids in tissue lipids from obese and lean rats. Ingestion of the HS compared with the LS diet resulted in increased proportions of 18∶2ω6 in liver lipids and adipose tissue triacylglycerols of obese and lean rats. The HS diet also increased the proportions of 20∶4ω6 in adipose triacylglycerols of obese and lean rats and in liver lipids of obese animals but not in their lean littermates.     

Effect of low levels of dietary fish oil on fatty acid desaturation and tissue fatty acids in obese and lean rats

The effect of very low levels of dietary long-chain n−3 fatty acids on Δ6 desaturation of linoleic acid (18∶2n−6) and α-linolenic acid (18∶3n−3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20∶3n−6), in liver microsomes and its influence on tissue fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing ca. 200 mg of long-chain polyunsaturated n−3 fatty acids per 100 g of diet were compared to those fed the same amount of α-linoleic acid. Low amounts of long-chain n−3 fatty acids greatly inhibited Δ6 desaturation of 18∶2n−6 and Δ5 desaturation of 20∶3n−6, while Δ6 desaturation of 18∶3n−3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the biosynthesis of long-chain n−6 fatty acids was reflected in a decrease in arachidonic acid (20∶4n−6) content of serum lipids when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids did not develop any decrease in 20∶4n−6 during fish oil ingestion. Docosahexaenoic acid (22∶6n−3), present in the dietary fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids.     

Effects of dietary triolein and sunflower oil on insulin release and lipid metabolism in zucker rats

Obese and lean male Zucker rats were fed ad libitum on diets containing either 50 (L) or 200 (H) g/kg diet of either triolein (T) or sunflowerseed oil (S). The specific activity of the hepatic microsomal Δ9 desaturase enzyme was depressed in both lean and obese rats fed the HS diet compared with the other three diets. The fatty acid composition of liver and subcutaneous white adipose tissue lipids were consistent with a lower Δ9 desaturation activity in rats fed the H diets, particularly for the HS diet. In both genotypes, microsomal Δ9 desaturase activity and the ratio of 16∶1/(16∶0+16∶1) fatty acids in liver lipids were inversely related to the proportion of 18∶2 in liver lipid. Plasma insulin concentrations and rates of glucose-stimulated insulin release in vivo were higher in obese rats compared with lean rats, and plasma insulin levels were higher in rats fed S compared with T. There was no relationship between Δ9 desaturase activity and either plasma insulin concentration or rates of insulin release in vitro. These findings suggest that hepatic Δ9 desaturase activity of Zucker rats is responsive to changes in the proportion of 18∶2 in liver lipids but is not affected by changes in insulin secretion.     

Differential alteration of Δ9 and Δ6 desaturation of fatty acids in rat brain preparations in vitro

Developing rat brain has the capacity for either Δ9 or Δ6 desaturation of fatty acids. In liver, evidence supports the existence of separate enzymes for each reaction, but it is not known whether in brain Δ9 or Δ6 desaturation of saturated fatty acids involves distinct enzymes. We have used fatty acids, including the cyclopropene fatty acid, sterculic acid, to alter desaturation activities with substrates that are desaturated predominantly in the Δ9 position or in the Δ6 position. In addition, differential alteration of desaturation of plamitic acid, a substrate that can be desaturated in either the Δ9 or Δ6 positions by brain preparations from neonatal rats, was examined. Sterculate reduced Δ9 desaturation of palmitate 80–90% but reduced Δ6 desaturation only 35%. In contrast, linoleic acid preferentially reduced Δ6 desaturation of palmitate. Thus, Δ9 desaturation of saturated fatty acids appears to be catalyzed by an enzyme or enzyme site distinct from that for Δ6 desaturation. Accordingly, these activities may be independently regulated during crucial stages of brain development.     

Daily variations of the biosynthesis and composition of fatty acids in rats fed on complete and fat-free diets

This report describes the daily changes in fatty acid composition and fatty acid desaturation in rats feeding on a complete diet and a fat-free diet successively. Rats on a complete diet showed a good homeostasis in the percentage of fatty acid in plasma, with a possible palmitic acid rhythm, but the fat-free diet initiated an essential fatty acid-deficient pattern in a few hours. The light-dark period in animals feeding on a complete diet motivates a feeding rhythm that causes changes in linoleic and arachidonic acids in the whole liver and microsomes that are related to Δ6 and Δ5 desaturase activities. The patterns of Δ6 and Δ5 desaturase changes were different. Linoleic acid intake during the dark periods (complete diet feeding) caused a decrease of Δ6 desaturase activity and the activation of Δ5 desaturation that led to an increase of arachidonic acid biosynthesis. The feeding of a fat-free diet eliminated the rhythm observed in linoleic and arachidonic acid composition in the liver and changed the desaturase rhythms. The Δ9 desaturase activity in the liver also showed a daily rhythm in the complete-diet period that disappeared with the change to a fat-free diet, while the activity increased markedly. A negative correlation existed between the percentage of linoleic acid in the liver and the Δ9 desaturase activity. However, no correlation was found between Δ9 desaturase activity and the percentage of 16∶1 and 18∶1 in the complete-diet period.     

The effects of a dietary oxidized oil on lipid metabolism in rats

This study was carried out to investigate the effects of a dietary oxidized oil on lipid metabolism in rats, particularly the desaturation of fatty acids. Two groups of rats were fed initially for a period of 35 d diets containing 10% of either fresh oil or thermally treated oil (150°C, 6d). The dietary fats used were markedly different for lipid peroxidation products (peroxide value: 94.5 vs. 3.1 meq O₂/kg; thiobarbituric acid-reactive substances: 230 vs. 7 μmol/kg) but were equalized for their fatty acid composition by using different mixtures of lard and safflower oil and for tocopherol concentrations by individual supplementation with dl-α-tocopherol acetate. In the second period which lasted 16 d, the same diets were supplemented with 10% linseed oil to study the effect of the oxidized oil on the desaturation of α-linolenic acid. During the whole period, all the rats were fed identical quantities of diet by a restrictive feeding system in order to avoid a reduced food intake in the rats fed the oxidized oil. Body weight gains and food conversion rates were only slightly lower in the rats fed the oxidized oil compared to the rats fed the fresh oil. Hence, the effects of lipid peroxidation products could be studied without a distortion by a marked reduced food intake and growth. To assess the rate of fatty acid desaturation, the fatty acid composition of liver and heart total lipids and phospholipids was determined and ratios between product and precursor of individual desaturation reactions were calculated. Rats fed the oxidized oil had reduced ratios of 20∶4n−6/18∶2n−6, 20∶5n−3/18∶3n−3, 20∶4n−6/20∶3n−6, and 22∶6n−3/22∶5n−3 in liver phospholipids and reduced ratios of 20∶4n−6/18∶2n−6, 22∶5n−3/18∶3n−3, and 22∶6n−3/18∶3n−3 in heart phospholipids. Those results suggest a reduced rate of desaturation of linoleic acid and α-linolenic acid by microsomal Δ4-, Δ5-, and Δ6-desaturases. Furthermore, liver total lipids of rats fed the oxidized oil exhibited a reduced ratio between total monounsaturated fatty acids and total saturated fatty acids, suggesting a reduced Δ9-desaturation. Besides those effects, the study observed a slightly increased liver weight, markedly reduced tocopherol concentrations in liver and plasma, reduced lipid concentrations in plasma, and an increased ratio between phospholipids and cholesterol in the liver. Thus, the study demonstrates that feeding an oxidized oil causes several alterations of lipid and fatty acid metabolism which might be of great physiologic relevance.     

Age-related changes in Δ6 and Δ5 desaturase activities in rat liver microsomes

Age-related changes in Δ6 desaturation of [1-¹⁴C]α-linolenic acid and [1-¹⁴C]linoleic acid and in Δ5 desaturation of [2-¹⁴C]dihomo-γ-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. Δ6 Desaturation of α-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-γ-linolenic acid to arachidonic acid by Δ5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span. The results suggest that, in liver, the activity of desaturases may be regulated in the course of aging to maintain a constant level of polyunsaturated fatty acids in cellular membranes.     

Effects of zinc deficiency and castration on fatty acid composition and desaturation in rats

The effects of zinc deficiency and testosterone on fatty acid composition of plasma lipids and microsomes of liver, intestine and testes were studied. The activities of fatty acid desaturase (Δ6 and Δ5) in rat liver and testes were also measured. A significant decrease in the level of arachidonic acid was observed in plasma of normal rats fed the zinc-deficient diet. Castration significantly decreased arachidonic acid but increased 20∶3 fatty acid, which is negligible in normal rats. Testosterone and zinc administration restored arachidonic acid to normal values. Zinc deficiency does not significantly change the fatty acid profile in liver, but castration decreased both arachidonic and 22∶6 fatty acid. Intestinal mucosal microsomes showed that the predominant fatty acid in this tissue, palmitic acid, is independent of zinc status, whereas polyunsaturated fatty acids 18∶2 and 20∶4 were decreased by zinc-deficient diet or castration. Zinc deficiency sharply decreased 22∶5 fatty acid and to some extent, other polyunsaturated fatty acids in testis microsomes. These changes in fatty acids are in agreement with increased Δ9 desaturation and decreased Δ5 desaturase activity. In testes, both Δ6 and Δ5 desaturase activities are decreased in zinc deficiency. It appears that zinc influences the conversion of linoleic to arachidonic acid, whereas testosterone influences Δ6 desaturase activity. The data suggest that zinc deficiency may be one of the important factors in the causation of polyunsaturated fatty acid deficiency, which in turn, may induce serum hypertriglyceridemia.     

Effect of epinephrine on the oxidative desaturation of fatty acids in the rat adrenal gland

Delta-6 and Δ5 desaturation activity of rat adrenal gland microsomes was studied to determine the effect of microsomal protein and the substrate saturation curves. This tissue has a very active Δ6 desaturase for linoleic and α-linoleic acids and a Δ5 desaturase for eicosa-8,11,14-trienoic acid. The administration of epinephrine (1 mg/kg body weight) 12 hr before killing, produced approximately a 50% decrease in desaturation of [1-¹⁴C]linoleic acid to γ-linolenic acid, [1-¹⁴C]α-linolenic acid to octadeca-6,9,12,15-tetraenoic acid and [1-¹⁴C]eicosa-8,11,14-trienoic acid to arachidonic acid. A 30% decrease in Δ5 desaturation activity was also shown after 7 hr of epinephrine treatment. The changes on the oxidative desaturation of the same fatty acids in liver microsomes were similar. No changes were observed in the total fatty acid composition of adrenal microsomes 12 hr after epinephrine treatment. Mechanisms of action of the hormone on the biosynthesis of polyunsaturated fatty acids in the adrenal gland are discussed.     

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, plama, 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 Δ-6, Δ-5 and Δ-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 Δ-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.     

Effect of different acids with Δ9,12-dienoic structures on Δ9 desaturation activity in rat liver microsomes

The effect of oral administration, for 24 or 48 hr, of different octadeca fatty acids containing a 9,12-dienoic structure on the fatty acid composition and Δ9 desaturation activity of liver microsomes of rat fed a fat-free diet was studied. The ethyl esters of linoelaidic and γ-linolenic acids, the methyl ester of linoleic acid and free columbinic acid were administered to rats maintained on a fat-free diet. The supplementation of the fat-free diet with linoelaidate produced no relevant changes in the fatty acid composition pattern of liver microsomes and did not modify the percentage of conversion of palmitic to palmitoleic acid. The addition of linoleate or γ-linolenate to the fat-free diet returned liver microsome Δ9 desaturation activity toward the control and partially restored the liver microsome fatty acid spectrum found in the fat-free diet. Columbinic acid (5-trans-9-cis,12-cis-18∶3), which cannot be transformed into arachidonic acid, also decreased the Δ9 desaturation activity enhanced by the fat-free diet and evoked changes in the microsomal fatty acid composition similar to those produced by the ω6 fatty acids. These results suggest that the modulation of Δ9 desaturase activity evoked by dietary administration of unsaturated acids of ω6 series would depend on thecis double bond configuration of these acids.     

Effect of environmental temperature changes on liver Δ6 and Δ5 fatty acid desaturases depressed by hyperglycidic diet on male rats

Male rats maintained on a control diet at 24 C and shifted to 12 C for five days showed no modification in Δ6 or Δ5 desaturase activity. When Δ6 and Δ5 desaturase activities were diminished by a hyperglycidic diet, shifting to cold increased both enzymatic activities. In general, modifications observed in liver microsomal fatty acid composition are consistent with those associated with the enzymatic desaturation activity.     

Pharmacological modulation of fatty acid desaturation and of cholesterol biosynthesis in THP-1 cells

In THP-1 cells, simvastatin decreases, in a concentration-dependent manner, cholesterol synthesis and increases linoleic acid (LA) conversion to its long-chain derivatives, in particular to arachidonic acid, activating Δ6 and Δ5 fatty acid (FA) desaturases. The intermediates in cholesterol synthesis, mevalonate and geranylgeraniol, partially reverse the effects of simvastatin on the LA conversion. The aims of this work were to evaluate: (i) the correlation between cholesterol synthesis and desaturase activity and (ii) the possible involvement of protein isoprenylation in desaturase activity, assessed through pharmacological treatments. THP-1 cells were incubated with [1-¹⁴C]LA or with [1-¹⁴C]di-homo-γ-linolenic acid (DHGLA) and treated with simvastatin or with curcumin and nicardipine, inhibitors of desaturases. Curcumin was more active than nicardipine in inhibiting LA and DHGLA conversion: 20 μM curcumin, alone or with simvastatin, totally inhibited Δ6 and Δ5 desaturation steps; 10 μM nicardipine only partially inhibited the enzymes, being more active on Δ5 desaturase. Simvastatin treatment decreased the incorporation of acetate in cholesterol (−93.8%) and cholesterol esters (−70.2%), as expected. Curcumin and nicardipine also decreased cholesterol synthesis and potentiated simvastatin. Finally, the isoprenylation inhibitors (perillic acid and GGTI-286) neither affected the conversion of LA nor inhibited the Δ5 desaturase activity. In conclusion, our results indicate that there is no direct relationship between cholesterol synthesis and desaturase activity. In fact, simvastatin decreased cholesterol synthesis and enhanced LA conversion (mainly Δ5 desaturation), whereas curcumin and nicardipin decreased Δ5 desaturation, with a limited effect on cholesterol synthesis.     

Liver Δ5 and Δ6 desaturase activity differs among laboratory rat strains

This study was designed to examine the variations among rat strains in hepatic fatty acid desaturase activities and to determine the correlations between the activities of these enzymes and the levels of each microsomal fatty acid. Wistar rats from two different sources as well as Long-Evans and Sprague-Dawley rats were selected to assess, under standard and identical experimental conditions, the liver Δ5 and Δ6 desaturase activities. Both desaturase activities were significantly reduced by 56% in Sprague-Dawley rats when compared to BB-Wistar control rats, whereas intermediate reduced values were detected in Wistar (CR) and Long-Evans strains. The activities of Δ5 and Δ6 desaturases were significantly and positively correlated with each other. However, no significant correlations were detected between either Δ5 or Δ6 desaturase activities and levels of any of their fatty acid substrates or any other of the major microsomal fatty acids. Fatty acid composition of microsomal total lipids showed strain dependency. A positive correlation was detected between the microsomal levels of the two major final products of both desaturases, namely 20∶4n−6 and 22∶6n−3. In general, the sum of n−3 or n−6 fatty acids but not the ratio of one to the other, varied among rat strains. The study demonstrated that Δ6 and Δ5 desaturase activities are strain-related. The data also suggested that (i) the desaturation activity should be measured and not predicted from the fatty acid composition and (ii) different rat strains should be used for lipid metabolic studies before conclusions are drawn for rats in general.     

Effect of age and α-linolenic acid deficiency on Δ6 desaturase activity and liver lipids in rats

The combined effects of age and of diet deficient in n−3 fatty acids on Δ6 desaturation of linoleic acid and on lipid fatty acid composition were studied in the liver of the rat at 2, 6, 12, 18 and 24 mon of age. The profiles of Δ6 desaturase activity and fatty acid composition were studied in the deficient rats refed, at these different ages either with 18∶3n−3 (mixture of peanut and rapeseed oils) or with 20∶5n−3+22∶6n−3 (fish oil) diets for 2, 4, 8 or 12 wk. Results showed that the liver Δ6 desaturation activity in the control rats remained high at 2 and 6 mon, decreased by 30% from 6 to 12 mon, and then remained stable from 12 to 24 mon. In the deficient rats, this activity remained high during the entire period studied. Thus, the profile of liver Δ6 desaturase activity after puberty was not related to age only; it also depended on the polyunsaturated fatty acid (PUFA) n−6 and n−3 balance in the diet. In the controls, in parallel with the Δ6 desaturase activity, PUFA metabolism could be divided into three periods: a “young” period, and “old age” period, separated by a period of transition between 6 and 12 mon. Recovery from PUFA n−3 deficiency occurred at all ages but in a different manner depending on whether the rats were “young” or “old”. Recovery was faster if long-chain n−3 PUFA rather than α-linolenic acid were supplied in the diet.     

Effects of age and dietary essential fatty acids on desaturase activities and on fatty acid composition of liver microsomal phospholipids of adult rats

The combined effects of age and dietary n−6 and n−3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18∶3n−6 (borage group) or 18∶3n−6 plus 18∶4n−3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18∶2n−6 and 18∶3n−3 only. For each group, Δ6, Δ5 and δ9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. Δ6 Desaturation of 18∶3n−3 was more sensitive to these factors while Δ6 desaturation of 18∶2n−6 and Δ9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.     

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 essential fatty acids was 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 Δ6 desaturation is inhibited more efficiently than the Δ5 and Δ4 desaturation. The chain elongation of essential C₁₈ fatty acids to their C₂₀ and C₂₂ homoglogs was not inhibited by norflurazon.     

Effect of polyunsaturated fatty acids of the α-linolenic series on the development of rat testicles

The effect of 22∶6ω3 acid provided by dietary fish oil on the development of germinal tissue of rat testes, fatty acid composition of lipids, and linoleic or α-linolenic acid Δ6 desaturation capacity was investigated. Results were compared to those obtained in animals fed methyl palmitate and sunflower seed oil (linoleate). At 7 and 9 weeks of age, development of germinal tissue of animals fed fish oil was normal. The fatty acid composition showed a decrease in 22∶5ω6 acid content and an increase in 22∶6ω3 acid in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. The fatty acid Δ6 desaturation capacity of testicules microsomes was increased. It is suggested that 22∶6ω3 acid may functionally replace 22∶5ω6 acid in germinal tissue.