Relationship between mouse liver Δ9 desaturase activity and plasma lipids

This study was undertaken to investigate the total plasma fatty acid composition and the relationship between plasma triacylglycerol (TG) levels and liver Δ9 desaturase activity in mice fed n−3 and/or n−6 fatty acid or hydrogenated coconut oil (HCO) (maximum 25 mg/g) supplemented diets. Generally, plasma TG levels and Δ9 desaturase activity were inversely correlated with the ratio of the sum of long chain n−3 fatty acids to 18∶2n−6 and to the ratio of the sum of long chain n−3 fatty acids to 18∶n−3, but they were positively correlated with the ratio of products and substrates (18∶1/18∶0) of the enzyme in plasma total lipids. The n−3 fatty acid (mainly 20∶5n−3) enriched diet, when compared to the HCO diet at 21 d, caused a significant reduction in plasma TG levels but not in Δ9 desaturase activity. However, a marked reduction in plasma TG content (50–60%) and Δ9 desaturase activity (55–70%) was observed when both 20∶5n−3 and 18∶3n−6 were supplemented in the diet. The plasma TG levels and Δ9 desaturase activity rose again when the animals were fed the HCO diet or chow. The results suggest that low dose supplementation of a mixture of n−3 (mainly 20∶5n−3) and n−6 (18∶3n−6) fatty acids modified both plasma TG content and liver Δ9 desaturase activity, in parallel.     

FA composition of cholesteryl esters and phospholipids in maternal plasma during pregnancy and at delivery and in cord plasma at birth

The purpose of this study was to assess the FA composition of both cholesteryl esters (CE) and phospholipids (PL) in maternal plasma during pregnancy and at delivery and in umbilical plasma at birth. A longitudinal study of 32 normal pregnant women was carried out with three cutoff points during pregnancy (first, second, and third trimester) and at delivery. Few significant differences occurred in the FA profile of maternal CE: 18∶1n−9 increased, 18∶2n−6 dropped slightly, and 18∶3n−3 decreased with progressing gestation. In maternal PL, long-chain highly unsaturated FA concentrations dropped and were replaced by saturated FA as gestation progressed. Additionally, changes in saturated FA in PL occurred: Shorter-chain 16∶0 was higher whereas longer-chain 18∶0 was lower at delivery compared to early pregnancy. The FA profile of umbilical venous plasma was strikingly different from that of maternal plasma at delivery. Cord plasma CE contained more saturated and monounsaturated FA than maternal CE. The polyunsaturates 18∶2n−6 and 18∶3n−3 are lower in umbilical CE than in maternal CE whereas 20∶4n−6 and 22∶6n−3 are twice as high in umbilical CE. Cord plasma PL have a higher content of long-chain highly unsaturated FA than maternal plasma PL at delivery. In contrast to maternal plasma PL, 16∶0 was lower and longer-chain saturated FA were higher in cord plasma PL. The FA profile of umbilical plasma at birth shows preferential accumulation of 20∶4n−6 and 22∶6n−3, with low concentrations of 18∶2n−6 and 18∶3n−3 in CE and PL, indicating a preferential supply of the fetus with long-chain highly unsaturated FA needed for fetal development.     

Hyperphagia modifies FA profiles of plasma phospholipids,plasma FFA,and adipose tissue TAG

Hyperphagia was achieved by continuous intracerebroventricular infusion of a melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats. The effects of hyperphagia on FA composition and concentration of plasma phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8 d [short-term hyperphagia (STH); n=8], or 28 d [longterm hyperphagia (LTH); n=9]. The control rats were treated with artificial cerebrospinal fluid for 8 d (n=8) or 28 d (n=10). The rats were fed the same regular diet. In STH rats the plasma PL and fasting plasma FFA contained higher concentrations of saturated FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n−6 PUFA than in the control rats. In LTH rats the plasma PL contained higher concentrations of SFA, MUFA, and n−3 PUFA and higher proportions of 16∶1n−7 and 18∶1n−9 at the expense of 18∶2n−6 than in the control rats. In LTH rats the abundant dietary intake of 18∶2n−6 did not enrich 18∶2n−6 of the plasma PL or adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than twofold higher concentrations of SFA and MUFA, and higher proportions of 16∶1n−7 and 18∶1n−9 at the expense of 18∶2n−6 than in the control rats. This animal obesity model shows that LTH affects the FA composition and concentration of plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes associated with increased risk of various diseases in humans. These results also demonstrate that LTH alters the FA composition of plasma PL and adipose tissue TAG in a way that does not reflect the FA composition of dietary fat.     

Distribution of polyunsaturated fatty acids including conjugated linoleic acids in total and subcellular fractions from healthy and cancerous parts of human kidneys

Differences in the FA composition of subcellular fractions from healthy and cancerous kidney tissues from the same patients were examined. Only minor differences in CLA content were found between the healthy and the cancerous tissue portions. Regarding the distribution pattern, CLA incorporation into nuclei and cytosol was significantly higher than incorporation into plasma membranes and mitochondria, which could be correlated to the neutral lipid content of these fractions. The subcellular distribution pattern of CLA was similar to that observed with monounsaturated FA but unlike that found with 18∶2n−6, which underlines the different physiological properties of CLA and 18∶2n−6. Because PUFA have been suggested to have an effect on cancer risk, the contents of n−3 and n−6 PUFA were determined in kidney and renal cell carcinoma (RCC). The 18∶2n−6 content and Δ⁵ desaturase activity were significantly lower, and the 18∶3n−6, 20∶3n−6, and 20∶5n−3 contents and Δ⁶ desaturase activity were significantly higher in RCC than in healthy renal tissue, indicating a changed PUFA metabolism in RCC. Previous research has suggested that CLA inhibits the elongation and desaturation of 18∶2n−6 into 20∶4n−6. In that case, one might speculate that a diet enriched in CLA would be a useful tool in preventing RCC. However, the involvement of CLA in preventing renal cancer could not be demonstrated definitively from the design of this experiment. Further understanding of the cause and/or consequence of the difference in FA metabolism may lead to a better understanding of RCC.     

Lipid class and fatty acid composition of the boreal soft coral Gersemia rubiformis

Total lipid, phospholipid, and FA composition and distribution of FA between polar lipids (PL) and neutral lipids (NL) were investigated in the boreal soft coral Gersemia rubiformis from the Bering Sea. The total lipids were mostly hydrocarbons and waxes (33.7%) and PL (33.1%). The content of monoalkyldiacylglycerols (9.7%) exceeded the content of TAG (6.7%). PC and PE constituted 31.4% and 25.6% of total phospholipids, respectively. Principal FA were 16∶0, 16∶1n−7, 18∶0, 18∶1n−9, 18∶1n−7, 20∶1n−7, 20∶4n−6, 20∶4n−3, 20∶5n−3 22∶5n−3, 22∶6n−3, 24∶5n−6, and 24∶6n−3. Most n−6 PUFA (52% of total FA) were associated with the PL fraction; this was especially true for arachidonic and tetracosapentaenoic acids. The NL were enriched with mono-, di-, trienoic, and n−3 PUFA. The variation in EPA levels in both NL and PL suggests an origin of this acid from lipids of diatoms consumed by the corals.     

Incorporation of n−3 fatty acids into WB-F344 cell phospholipids inhibits gap junctional intercellular communication

In this investigation, we demonstrate that rat liver epithelial (WB-F344) cells grown in medium supplemented with n−3 fatty acids (FA) results in the inhibition of gap junctional intercellular communication (GJIC). Cells incubated for 48 hr in medium containing 50 μM α-linolenate (18∶3n−3) resulted in a 60% inhibition of GJIC, compared to control cells, while treatment with γ-linolenate (18∶3n−6) had no effect. Supplementation with octadecatetraenoate (18∶4n−3), eicosapentaenoate (20∶5n−3), and docosahexaenoate (22∶6n−3), inhibited GJIC by 42%, 28%, and 18%, respectively. Incubation with each of the n−3 FA markedly increased the total n−3 FA content of cellular phospholipids (PL). Growing cells in medium containing 50 μM arachidonate (20∶4n−6) plus 50 μM 18∶3n−3 partially attenuated the inhibition of GJIC induced by 18∶3n−3. The mechanism by which n−3 FA inhibit GJIC remains to be determined.     

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.     

Fatty acid composition of late embryonic and early postnatal rat brain

The fatty acid (FA) composition and distribution in a variety of phospholipids (PL) and neutral lipids (NL) at two discrete stages during the embryonic rat brain development were investigated. Over 96% of the FA were acylated into fetal brain PL at embryonic day 17 after the peak of neuronal proliferation and at embryonic day 20, one day prior to delivery. Phosphatidylcholine constituted approximately 60% of the total PL pool, phosphatidylethanolamine (PE) 30%, phosphatidylserine (PS) 6%, and phosphatidylinositol (PI) 4%. The diacylglycerols and triacylglycerols constituted 1–2% of the fetal brain lipids. α-Linolenic acid (18∶3n−3) and linoleic acid (18∶2n−6) were found in very low amounts in all fetal brain PL and NL. The percentage of the n−6 polyunsaturated FA, consisting of arachidonic acid (AA), 22∶4n−6 and 22∶5n−6, remained unchanged in all the fractions, except in Pl, in which the proportion of AA increased. The concentration of docosahexaenoic acid (DHA) increased with age in all the fractions, with the bulk of accumulation accounted for by its increase in PE and, to a lesser extent, in PS. This finding suggests a “DHA accretion spurt” during the last three days of pregnancy.     

Paradoxical effect of n−3-containing vegetable oils on long-chain n−3 fatty acids in rat heart

Flaxseed, echium, and canola oils contain α-linolenic acid (18∶3n−3, ALA) in a range of concentrations. To examine their effect on elevating cardiac levels of long-chain n−3 FA, diets based on these n−3-containing vegetable oils were fed to rats for 4 wk. Sunflower oil, which contains little ALA, was a comparator. Despite canola oil having the lowest ALA content of the three n−3-containing vegetable oils, it was the most potent for elevating DHA (22∶6n−3) levels in rat hearts and plasma. However, the relative potencies of the dietary oils for elevation of EPA (20∶5n−3) in heart and plasma followed the same rank order as their ALA content, i.e., flaxseed>echium>canola>sunflower oil. This paradox may be explained by lower ALA intake leading to decreased competition for Δ6 desaturase activity between ALA and the 24∶5n−3 FA precursor to DHA formation.     

Desaturase activities in rat model of insulin resistance induced by a sucrose-rich diet

A sucrose-rich diet, as compared with a similar starch diet, induces a time-dependent typical noninsulin-dependent diabetes syndrome characterized by insulin resistance in rats. Within the first 3 wk, there was glucose intolerance associated with hyperinsulinemia, hypertriglyceridemia, and high plasma FFA. In this study, we examined the effect of the sucrose-rich diet vs. the starch diet during short-(3 wk) and long-term treatment (6 mon) on hepatic Δ9, Δ6, and Δ5 desaturases. These enzymes modulate monounsaturated FA and PUFA biosynthesis, respectively. Sucrose feeding (3 wk) caused an initial hyperinsulinemia that was normalized within 6 mon. In the early period (3 wk), stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity were decreased, whereas Δ6 desaturase mRNA abundance and Δ6 and Δ5 desaturase activities remained unchanged. After 6 mon of sucrose feeding, activities of the Δ9, Δ6, and Δ5 desaturases were each increased. The SCD-1 and Δ6 desaturase mRNA were also correspondingly higher. These increases were consistent with an increase in oleic acid, the 20∶4/18∶2 ratio, and 22∶4n−6 and 22∶5n−6 acids in liver and muscle lipids. On the other hand, the percentage of 22∶6n−3 acid was decreased. In conclusion, a sucrose-rich diet after 6 mon induces an increase in rat liver SCD-1 and Δ6 desaturase mRNA and enzymatic activities that are opposite to the changes reported in insulin-dependent diabetes mellitus. It appears that neither blood insulin levels nor insulin resistance is a factor affecting the Δ9, Δ6, and Δ5 desaturase changes in mRNA and activity found with the sucrose-rich diet.     

Effects of dietary fats on fatty acid composition and Δ5 desaturase in normal and diabetic rats

We have studied the effect of various diets on the phospholipid fatty acid composition andin vitro Δ5 desaturase activity of hepatic microsomes derived either from the normal or streptozotocin-induced diabetic rat. The diets studied were the standard rat chow diet and a basal fat-free diet supplemented either with 20 percent saturated fat, 20 percent unsaturated fat, or 20 percent menhaden oil. Phospholipid fatty acid composition analysis revealed that the normal rat fed the saturated fat or menhaden oil diet had significantly decreased arachidonate levels, consistent with decreased Δ5 desaturase activities and decreased 18∶2n−6 intake. On the contrary, the unsaturated fat diet decreased dihomo-γ-linolenate and increased arachidonate levels, without increased Δ5 desaturase activity. Streptozotocininduced diabetes resulted in decreased arachidonate and Δ5 desaturase activity. The unsaturated fat diet fed to the diabetic rat also failed to correct this decreased Δ5 desaturase activity. The unsaturated fatty acids in this diet also displaced a substantial amount of n−3 fatty acids in both normal and diabetic microsomes, due to the competition between these two fatty acid families for incorporation into the membrane phospholipids. Conversely, the menhaden oil diet fed to the normal and diabetic rats displaced n−6 fatty acids, reduced Δ5 desaturase activity, and enhanced 22∶6n−3 incorporation into diabetic microsomes.     

Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat

The effects of clofibrate on the content and composition of liver and plasma lipids were studied in mice fed for 4 wk on diets enriched in n−6 or n−3 polyunsaturated fatty acids (PUFA) from sunflower oil (SO) or fish oil (FO), respectively; both oils were fed at 9% of the diet (dry weight basis). Only FO was hypolipidemic. Both oil regimes led to slightly increased concentrations of phospholipids (PL) and triacylglycerols (TG) in liver as compared with a standard chow diet containing 2% fat. Clofibrate promoted hypolipidemia only in animals fed SO. Its main effect was to enlarge the liver, such growth increasing the amounts of major glycerophospholipids while depleting the TG. SO and FO consumption changed the proportion of n−6 or n−3 PUFA in liver and plasma lipids in opposite ways. After clofibrate action, the PUFA of liver PL were preserved better than in the absence of oil supplementation. However, most of the drug-induced changes (e.g., increased 18∶1n−9 and 20∶3n−6, decreased 22∶6/20∶5 ratios) occurred inrrespective of lipids being rich in n−6 or n−3 PUFA. The concentration of sphingomyelin (SM), a minor liver lipid that virtually lacks PUFA, increased with the dietary oils, decreased with clofibrate, and changed its fatty acid composition in both situations. Thus. oil-increased SM had more 22∶0 and 24∶0 than clofibrate-decreased SM, which was significantly richer in 22∶1 and 24∶1.     

Fatty acid metabolism in marine fish: Low activity of fatty acyl Δ5 desaturation in gilthead sea bream (Sparus aurata) cells

Marine fish have an absolute dietary requirement for C₂₀ and C₂₂ highly unsaturated fatty acids. Previous studies using cultured cell lines indicated that underlying this requirement in marine fish was either a deficiency in fatty acyl Δ5 desaturase or C_18–20 elongase activity. Recent research in turbot cells found low C_18–20 elongase but high Δ5 desaturase activity. In the present study, the fatty acid desaturase/elongase pathway was investigated in a cell line (SAF-1) from another carnivorous marine fish, sea bream. The metabolic conversions of a range of radiolabeled polyunsaturated fatty acids that comprised the direct substrates for Δ6 desaturase ([1-¹⁴C]18∶2n−6 and [1-¹⁴C]18∶3n−3), C_18–20 elongase ([U-¹⁴C]18∶4n−3), Δ5 desaturase ([1-¹⁴C]20∶3n−6 and [1-¹⁴C]20∶5n−3), and C_20–22 elongase ([1-¹⁴C]20∶4n−6 and [1-¹⁴C]20∶5n−3) were utilized. The results showed that fatty acyl Δ6 desaturase in SAF-1 cells was highly active and that C_18–20 elongase and C_20–22 elongase activities were substantial. A deficiency in the desaturation/elongation pathway was clearly identified at the level of the fatty acyl Δ5 desaturase, which was very low, particularly with 20∶4n−3 as substrate. In comparison, the apparent activities of Δ6 desaturase, C_18–20 elongase, and C_20–22 elongase were approximately 94-, 27-, and 16-fold greater than that for Δ5 desaturase toward their respective n−3 polyunsaturated fatty acid substrates. The evidence obtained in the SAF-1 cell line is consistent with the dietary requirement for C₂₀ and C₂₂ highly unsaturated fatty acids in the marine fish the sea bream, being primarily due to a deficiency in fatty acid Δ5 desaturase activity.     

Effects of dietary supplementation of rapeseed oil on metabolism of [1-<Superscript>14</Superscript>C]18∶1n−9, [1-<Superscript>14</Superscript>C]20∶3n−6, and [1-<Superscript>14</Superscript>C]20∶4n−3 in atlantic salmon heaptocytes

Atlantic salmon were fed fish meal-based diets supplemented with either 100% fish oil (FO) or 100% rapeseed oil (RO) from an initial weight of 85 g to a final average weight of 280 g. The effects of these diets on the capacity of Atlantic salmon hepatocytes to elogate, desaturate, and esterify [1-¹⁴C]18∶1n−9 and the immediate substrates for the Δ⁵ desaturase, [1-¹⁴C]20∶3 n−6 and [1-¹⁴C]20∶4n−3, were investigated. Radiolabeled 18∶1n−9 was mainly esterified into cellular TAG, whereas the more polyunsaturated FA, [1-¹⁴C]20∶3n−6 and [1-¹⁴C]20∶4n−3, were primarily esterified into cellular PL. More of the elongation product, [1-¹⁴C]20∶1n−9, was produced from 18∶1n−9 and more of the desaturation and elongation products, 22∶5n−6 and 22∶6n−3, were produced from [1-¹⁴C]20∶3n−6 and [1-¹⁴C]20∶4n−3, respectively, in RO hepatocytes than in FO hepatocytes. Further, we studied whether increased addition of [1-¹⁴C]18∶1n−9 to the hepatocyte culture media would affect the capacity of hepatocytes to oxidize 18∶1n−9 to acid-soluble products and CO₂. An increase in exogenous concentration of 18∶1n−9 from 7 to 100 μM resulted in a nearly twofold increase in the amount of 18∶1n−9 that was oxidized. The conversion of 20∶4n−3 and 20∶3n−6 to the longer-chain 22∶6n−3 and 22∶5n−6 was enhanced by RO feeding in Atlantic salmon hepatocytes. The increased capacity of RO hepatocytes to produce 22∶6n−3 was, however, not enought to achieve the levels found in FO hepatocytes. Our data further showed that there were no differences in the hepatocyte FA oxidation capacity and the lipid deposition of carcass and liver between the two groups.     

Dietary α-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels

Fish oil-enriched diets increase n−3 FA in tissue phospholipids; however, a similar effect by plant-derived n−3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18∶3n−3), fish oil (rich in 22∶6n−3 and 20∶5n−3), or safflower oil (rich in 18∶2n−6) for 8 wk. In the heart and liver phospholipids, 22∶6n−3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20∶5n−3 and 22∶5n−3. However, in the brain, the flax and fish oil diets increased the phospholipid 22∶6n−3 mass. In all tissues, these diets decreased the 20∶4n−6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18∶3n−3 elongation and desaturation by the brain, they demonstrate that 18∶3n−3-enriched diets reduced tissue 20∶4n−6 levels and increased cellular n−3 levels in a tissuedependent manner. We hypothesize, based on the lack of increased 22∶6n−3 but increased 18∶3n−3 in the liver and heart, that the flax oil diet increased circulating 18∶3n−3, thereby presenting tissue with this EFA for further elongation and desaturation.     

Thermal adaptation affects the fatty acid composition of plasma phospholipids in trout

The adaptive changes in the fatty acid (FA) composition of plasma phospholipids (PL) in response to alterations in environmental water temperature were investigated in juvenile rainbow trout (Oncorhynchus mykiss). The changes observed during thermal adaptation from 22°C in summer to 8°C in winter were reproduced by laboratory cold acclimation (CA) at 6°C of 22°C-summer-acclimated animals. In cold-acclimated and winter-acclimated trout, the increase in the unsaturation of PL fatty acids was mainly due to an enrichment of approximately 7% in the total weight percentage of 22∶6n−3, while a concomitant significant decrease in the levels of 18∶0 and of the monoenoic n−9 FA was observed. A time course study revealed that the changes in PL fatty acids became significant after 10 d of CA and were complete after one month. These changes in the composition of the fatty acyl chains of plasma total PL indicate that the FA composition of plasma lipoprotein PL does not remain constant during thermal adaptation. This would suggest that plasma lipoproteins provide a rapid systemic supply of lipids containing more or less unsaturated FA during thermal adaptation of poikilothermic animals.     

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.     

Liver desaturase activities and FA composition in monkeys. Effect of a low-protein diet

The aim of the present study was to measure Δ9-, Δ6-, and Δ5-desaturase activities in liver microsomes, as well as phospholipid FA composition of liver and erythrocytes in monkeys fed a control or low-protein diet during the postweaning period. Ten Saimiri sciureus boliviensis (Cebidae) of both sexes were employed; at 12 mon of age they were separated into two groups fed ad libitum on a control or a low-protein diet for 24 mon. Saimiri sciureus had active Δ9, Δ6, and Δ5 liver desaturase enzymes, and these activities were influenced by the diet. A low-protein diet produced a significant reduction in Δ5-desaturation capacity, an increase in Δ9-desaturase activity, and no change in Δ6-desaturase activity (P<0.05). These changes, evoked by protein deprivation, were reflected in the liver phospholipid FA composition. Increases in the proportion of saturated FA and in monounsaturated oleic acid (18∶1n−9) and a decrease in the proportion of PUFA of the n−6 and n−3 series were produced in the animals fed a low-protein diet (P<0.0001). Differences between the two dietary groups were less pronounced in the FA composition of erythrocyte phospholipids. The authors are members of the Carrera del Investigador del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.     

Dose effect of α-linolenic acid on PUFA conversion,bioavailability, and storage in the hamster

If an increased consumption of α-linolenic acid (ALA) is to be promoted in parallel with that of n−3 long-chain-rich food, it is necessary to consider to what extent dietary ALA can be absorbed, transported, stored, and converted into long-chain derivatives. We investigated these processes in male hamsters, over a broad range of supply as linseed oil (0.37, 3.5, 6.9, and 14.6% energy). Linoleic acid (LA) was kept constant (8.5% energy), and the LA/ALA ratio was varied from 22.5 to 0.6. The apparent absorption of individual FA was very high (>96%), and that of ALA remained almost maximum even at the largest supply (99.5%). The capacity for ALA transport and storage had no limitation over the chosen range of dietary intake. Indeed, ALA intake was significantly correlated with ALA level not only in cholesteryl esters (from 0.3 to 9.7% of total FA) but also in plasma phospholipids and red blood cells (RBC), which makes blood components extremely reliable as biomarkers of ALA consumption. Similarly, ALA storage in adipose tissue increased from 0.85 to 14% of total FA and was highly correlated with ALA intake. As for bioconversion, dietary ALA failed to increase 22∶6n−3, decreased 20∶4n−6, and efficiently increased 20∶5n−3 (EPA) in RBC and cardiomyocytes. EPA accumulation did not tend to plateau, in accordance with identical activities of Δ5- and Δ6-desaturases in all groups. Dietary supply of ALA was therefore a very efficient means of improving the 20∶4n−6 to 20∶5n−3 balance.     

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.