Relation of fatty acid composition in lead-exposed mallards to fat mobilization,lipid peroxidation and alkaline phosphatase activity

The increase of n-6 polyunsaturated fatty acids (PUFA) in animal tissues has been proposed as a mechanism of lead (Pb) poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fatty acid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for 3 weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with decreased triglycerides and increased cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fatty acid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.     

Lead-induced tissue fatty acid alterations and lipid peroxidation

Previous work showed that dietary lead (Pb) increases the relative concentration of arachidonic acid (20∶4) as a percentage of total fatty acids, and decreases the relative proportion of linoleic acid (18∶2) to arachidonic acid (18∶2/20∶4) in chick liver, serum, and erythrocyte membranes. The present investigation was undertaken to examine the time-course and magnitude of the fatty acid alterations with increasing dietary Pb levels. We also examined the effects of Pb on the fatty acid composition and lipid peroxide content of hepatic subcellular organelles. In Exp. 1, chicks were fed diets containing 0, 62.5, 125, 250, 500, or 1000 ppm added Pb (as Pb acetate trihydrate) from 1 to 21 d of age. After 21 d, no growth effects were observed; however, Pb lowered the 18∶2/20∶4 ratio and increased 20∶4 concentration in total liver and serum lipids, and in total hepatic phospholipids in a dose-dependent manner. Hepatic mitochondrial membrane fatty acids were not altered, nor was there any increase in hepatic lipid peroxidation. In Exp. 2, chicks were fed diets containing 0, 500, 1000, or 2000 ppm added Pb from 1 to 21 or 22 d of age. Pb depressed growth in a dose-dependent manner. In addition, Pb lowered the 18∶2/20∶4 ratio and increased 20∶4 concentration in total liver lipids and in hepatic mitochondrial and microsomal membranes in a dose-dependent manner. Total hepatic lipid peroxidation was increased over control values by 1000 ppm Pb, and hepatic microsomal lipid peroxidation was increased by dietary Pb levels of 1000 and 2000 ppm. In Exp. 3, body weight, hepatic microsomal lipid peroxidation, and fatty acid composition were determined in 4-, 9-, 14-, 18-, and 23-d-old chicks fed 0 or 1500 ppm added Pb. Body weights of Pb-treated chicks were significantly lower than those of control chicks by day 18. Microsomal 20∶4 concentration and peroxidation increased, and the 18∶2/20∶4 ratio decreased with age in both groups, but the changes were of greater magnitude in the Pb-treated chicks. The results suggest that some of the manifestations of Pb toxicity may be a reflection of increased concentration of 20∶4 in specific membranes. Further, since the Pb-induced alterations in fatty acid composition were noted in the absence of any growth depression, we propose that fatty acid composition is more sensitive than growth rate to the presence of lead in the diet.     

Lead disrupts eicosanoid metabolism, macrophage function, and disease resistance in birds

Lead (Pb) affects elements of humoral and cell-mediated immunity, and diminishes host resistance to infectious disease. Evidence is presented supporting a hypothesis of Pb-induced immunosuppression stemming from altered fatty acid metabolism, and mediated by eicosanoids and macrophages (MØ). Chronic Pb exposure increases the proportion of arachidonate (ArA) among fatty acids in lipid from avian tissues, and this change provides precursors for eicosanoids, the oxygenated derivatives of ArA that mediate MØ acute inflammatory response. In the current study, we showed that the concentration of ArA in phospholipids of MØ elicited from turkey poults fed 100 ppm dietary Pb acetate was twice that of controls. In vitro production of eicosanoids by these MØ was substantially increased, and this effect was most pronounced following lipopolysaccharide stimulation: prostaglandin F_2α was increased 11-fold, thromboxane B₂ increased threefold, and prostaglandin E₂ increased by 1.5 times. In vitro phagocytic potential of these MØ was suppressed, such that the percentage of MØ engulfing sheep red blood cell (RBC) targets was reduced to half that of control MØ. In vivo susceptibility of Pb-treated and control birds to Gram-negative bacteria challenge was also evaluated. The morbidity of chicks inoculated withSalmonella gallinarum and fed either control or 200 ppm Pb acetate-supplemented diets was similar, except early in the course of the disease when mortality among Pb-treated birds was marginally greater. In these studies, effects of Pb that could influence immunological homeostasis were demonstrated for MØ metabolism of ArA, for production of eicosanoids, and for phagocytosis. There was also the suggestion that these in vitro indices of immune function are related to in vivo disease resistance.     

Effects of dietary lead,cadmium, mercury,and selenium on fatty acid composition of blood serum and erythrocyte membranes from chicks

A series of experiments was conducted to study the effects of dietary and injected lead (as Pb acetate-3H₂O) and of dietary Cd, Hg, and Se on fatty acid composition of serum lipids of chicks as measured by gas-liquid chromatography. The effect of dietary Pb on fatty acid composition of erythrocyte membranes was measured also. Dietary Pb (1000 ppm) increased the serum concentration of arachidonic acid (20:4, first no. = no. of carbon atoms:second no. = no. of double bonds) and decreased the concentration of linoleic acid (18:2) and the ratio 18:2/20:4. Intraperitoneal injection of Pb (52 mg/100 g body weight) did not alter serum fatty acid composition by 4 h post-injection. The separate effects of 2000 ppm Pb, 60 ppm Cd, 500 ppm Hg, and 10 ppm Se added to the diet on serum fatty acids were measured in a single experiment. In comparison to controls, Pb and Cd lowered serum concentration of 18:2. Only Pb raised serum 20:4. Pb lowered the ratio 18:2/20:4, whereas Cd and Hg raised the ratio and Se was without effect. Dietary Pb (2000 ppm) raised the concentration of 20:4 and lowered the ratio 18:2/20:4 in erythrocyte membranes. The different effects of injected and dietary Pb on the serum 18:2/20:4 ratio suggest that Pb alters 20:4 synthesis from 18:2 rather than mobilization of 20:4 from tissues. The Pb-induced increase of lipid peroxida-tion in erythrocytes observed by other workers may be a reflection of increased 20:4 level in erythrocyte membranes.     

Effect of dietary nucleotides and orotate on the blood levels of prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat

Dietary nucleotides affect the maintenance of immune responses, tissue repair and polyunsaturated fatty acid metabolism. Orotate, a pyrimidine nucleotide precursor, induces fatty livers by impairing VLDL hepatic secretion. The aim of this study was to evaluate the changes in the blood levels of fatty acids and prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat caused by the dietary intake of nucleotides and orotate. Three groups of rats at weaning were fed a control diet, an orotate supplemented diet (O-50) and a nucleotide supplemented diet (N-50) during 4 weeks, respectively. Absolute values of plasma polyunsaturated fatty acids greater than 18 carbon atoms of the n-6 and n-3 series were increased in the N-50 group and decreased in O-50 with regard to the control. However, the relative fatty acid composition of plasma lipid fractions was mostly unaffected. Plasma 6-keto-PGF1 alpha showed a trend to be increased in N-50 and serum TXB2 was significantly increased in that group. Both eicosanoids were unchanged by dietary orotate intake. These results may be explained because of the increased plasma 20:4n-6 found in rats fed a supplemented nucleotide diet. Thus, nucleotides present in foods appear to modulate PUFA conversion and eicosanoids synthesis in early life.     

Effects of dietary lead,fish oil,and ethoxyquin on hepatic fatty acid composition in chicks

Three experiments were conducted with day-old broiler chicks reared to 18 or 19 d of age. The objective was to examine the effects of dietary oil (cottonseed oil vs fish oil), dietary antioxidant (0 vs 75 ppm ethoxyquin), and dietary lead (0 vs 1000 ppm Pb as lead acetate trihydrate) on hepatic fatty acid composition. A 2×2 factorial arrangement was used in all experiments. In Experiment 1, the factors were oil (4% of each) and Pb. In Experiments 2 and 3, the factors were ethoxyquin and Pb in diets containing 3.5% cottonseed oil (Experiment 2) or 3.5% fish oil (Experiment 3). Hepatic fatty acid profiles were measured by gas-liquid chromatography in 10 chicks/treatment (Experiment 1) or 4 chicks/treatment (Experiments 2 and 3). Dietary oils altered the profiles, with cottonseed oil producing the higher values for linoleic acid (18∶2) and arachidonic acid (20∶4). With fish oil, in addition to the lower levels of 18∶2 and 20∶4, there were significant levels of eicosapentaenoic acid (20∶5) and docosahexaenoic acid (22∶6). Pb enhanced the levels of 20∶4, but the effect was greater with cottonseed oil diets compared with fish oil diets. The enhanced 20∶4 levels resulted in lower ratios of 18∶2/20∶4. Ethoxyquin enhanced the level of 18∶2 with the cottonseed oil diet, and of 20∶5 and 22∶6 with the fish oil diet. Ethoxyquin decreased the level of hepatic 20∶4 when fish oil was fed. The results clearly show that all three factors (oil type, Pb level, and ethoxyquin level) after hepatic fatty acid composition. Both oil source and Pb level appeared to exert an effect on the metabolic conversion of 18∶2 and 20∶4. The primary effect of ethoxyquin was to enhance the levels of polyunsaturated fatty acids in liver. The data do not allow the partitioning of possible ethoxyquin effects to protection of polyunsaturated acids in feed vs protection of polyunsaturated acids in liver tissue. Use of trade names implies neither approval by the North Carolina Agricultural Research Service of products named nor criticism of products not named.     

Schistosoma mansoni: eicosanoid production by cercariae

Cercariae of Schistosoma mansoni are stimulated to penetrate skin by certain free fatty acids. The cercariae have an active arachidonate cascade, presumably using host skin essential fatty acids as cascade precursors. Exposing cercariae to 3.3 mM linoleate for 1, 10, and 60 min resulted in production of a wide variety of eicosanoids. Using high-performance liquid chromatography, eicosanoids coeluting with prostaglandin E2, D2, and A2, leukotriene B4, and 5-hydroxyeicosatetraenoic acid standards were identified, as well as unidentified peak positions. Radioimmunoassay confirmed the presence of immunoreactive prostaglandin E1, and E2, and 5- and 15-hydroxyeicosatetraenoic acids in cercarial extracts. No eicosanoid production occurred when cercariae were exposed to 3.3 mM oleate and 1 or 330 microM linoleate. Both high-performance liquid chromatography and radioimmunoassay data indicated that cercariae regulate the production of eicosanoids through time. It is postulated that arachidonate metabolism and subsequent eicosanoid production are required for successful cercarial penetration.     

Effects of low magnesium diet on the vascular prostaglandin and fatty acid metabolism in rats

Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.     

Differential effects of Mg2+ on various hydrolytic and synthetic activities of multifunctional glucose-6-phosphatase

The adaptive synthesis of fatty acid synthetase in the livers of rats fed a fat-free diet following 48 hr of fasting has been studied using immunochemical methods. The development of fatty acid synthetase activity during adaptive synthesis occurs about 3 hr following feeding, whereas the synthesis of material precipitable by anti-fatty acid synthetase serum, as judged by the incorporation of ³H-labeled amino acids into the immunoprecipitate, commenced within 1 hr. Extracts of liver of rats fed a fat-free diet for 1–3 hr following fasting contain increasing amounts of material which competes with purified fatty acid synthetase for antibody binding sites, even though they have no fatty acid synthetase activity. This suggests the presence of enzymatically inactive precursors of fatty acid synthetase in the liver extracts. The incorporation of [¹⁴C]pantothenate into fatty acid synthetase during adaptive synthesis follows the same pattern as the development of enzyme activity, indicating that these enzymatically inactive precursors of fatty acid synthetase may represent an apoenzyme which is converted to the enzymatically active holoenzyme by the incorporation of the 4′-phosphopantetheine prosthetic group. The subcellular site of synthesis of fatty acid synthetase was shown to be in the pool of polysomes that are not membrane bound, rather than in the rough endoplasmic reticulum.     

Lipidomic approaches to the study of phospholipase A2-regulated phospholipid fatty acid incorporation and remodeling

The distribution of fatty acids among cellular glycerophospholipids is finely regulated by the CoA-dependent acylation of lysophospholipids followed by transacylation reactions. Arachidonic acid is the fatty acid precursor of a wide family of bioactive compounds called the eicosanoids, with key roles in innate immunity and inflammation. Because availability of free AA constitutes a rate-limiting step in the generation of eicosanoids by mammalian cells, many studies have been devoted to characterize the processes of arachidonate liberation from phospholipids by phospholipase A₂s and its re-incorporation and further remodeling back into phospholipids by acyltransferases and transacylases. These studies have traditionally been conducted by using radioactive precursors which do not allow the identification of the phospholipid molecular species involved in these processes. Nowadays, lipidomic approaches utilizing mass spectrometry provide a new frame for the analysis of unique phospholipid species involved in fatty acid release and phospholipid incorporation and remodeling. This review focuses on the mass spectrometry techniques applied to the study of phospholipid fatty acid trafficking and the recent advances that have been achieved by the use of this technique.     

Changes in fatty acid composition of lipids from birds, rodents, and preschool children exposed to lead

Chronic treatment with inorganic lead (Pb) has been shown to increase the proportion of arachidonic acid (ArA), as well as the arachidonate/linoleate (ArA/LA) ratio, in the fatty acids of lipids from a variety of avian tissues. Changes in two fatty acid-mediated phenomena, peroxidation of membrane lipids and synthesis of eicosanoid cytokines, are associated with this enhanced ArA content. The authors are not aware of any reports in the literature in which these effects of Pb have been described for any animals other than birds. In the current study, the authors investigated the effect of Pb on lipid metabolism in three species: avian, rodent, and human. The group of children identified as suffering environmental Pb exposure were from a Pb-surveillance program and had blood Pb concentrations (PbB) averaging 23 μg/dL. Turkey poults fed 100 ppm dietary Pb as Pb acetate-trihydrate for 19 d had a PbB of 46 μg/dL. Gastric intubation of rats with 80 mg Pb/kg/d for 10 d resulted in a PbB of 74 μg/dL. We analyzed fatty acid composition of whole blood from children, poults, and virgin rats. Low-dose (nongrowth inhibitory) Pb exposure resulted in significantly increased ArA concentration and ArA/LA ratio in blood from all species. Also analyzed were plasma and liver of poults, virgin rats, and pregnant rats and their fetuses. In plasma and liver from Pb-treated poults and virgin rats, ArA and the ArA/LA ratio were again enhanced. Pb intoxication also affected ω3 composition, increasing the concentrations of all long-chain ω3 fatty acids of fetuses from Pb-treated pregnant dams. The authors propose that altered fatty acid metabolism may be responsible for some indications of Pb poisoning. Possible consequences mediated through lipid peroxidation and production of ArA-derivative eicosanoids are considered.     

Effects of acute and chronic ethanol administration on thromboxane and prostacyclin levels and release in rat brain cortex

The effects of acute (3 g/kg i.p. two hours before sacrifice) and chronic (6% in drinking water and libitum for 15 days) ethanol administration to male rats (200 g body weight) on basal levels and release of TxB2 and 6-keto-PGF1 alpha in brain cortex were studied. Also the effects of chronic ethanol (30 days) on the fatty acid composition of brain cortical tissue and liver phospholipids were investigated. Acute treatment reduced basal levels of 6-keto- PGF1 alpha in brain cortical tissue (rats sacrificed by microwave radiation) and decreased the accumulation of 6-keto-PGF1 alpha in brain cortex after post-decapitation ischemia (PDI). Basal TxB2 levels were also reduced in brain cortex, but TxB2 release during PDI was enhanced. Chronic treatment (15 days) induced changes of TxB2 and 6-keto-PGF1 alpha levels and release during PDI in brain cortex less pronounced than those observed after acute treatment. The reduced effectiveness of chronic ethanol on brain vasoactive eicosanoids suggest adaptation processes. After chronic treatment (30 days), the fatty acid composition of brain cortex total phospholipids were not significantly modified. Changes of eicosanoid production after ethanol were thus independent from modifications of the fatty acid precursor pool(s). Ethanol-induced changes in the production of vascular eicosanoids in the CNS may be of relevance to the action of the compound on the CNS and may also have implications for the clinic.     

Arachidonate-dependent oxygen consumption in Dictyostelium discoideum

A central feature of the processes of aggregation and differentiation in the cellular slime mould Dictyostelium discoideum is the periodic excitatory cycle. Originally thought to involve primarily fluctuations in cyclic AMP levels, this excitatory cycle has since been shown to involve changes in several other second messengers including cyclic GMP, calcium and inositol trisphosphate. Previous work from this laboratory using specific inhibitors strongly suggested a role for eicosanoids in this stimulus-response process. Production of eicosanoids from fatty acid precursors is an oxygen-consuming process. In this paper, we report on oxygen consumption measurements in intact D. discoideum cells and in cell extracts. We demonstrate the existence of an azide-insensitive component of oxygen consumption which can be stimulated by the addition of arachidonate and other polyunsaturated fatty acids, and at least partially inhibited by meclofenamate and eicosatetraynoic acid, both of which block eicosanoid biosynthesis in higher organisms. These observations provide further evidence for the existence of an eicosanoid-metabolizing system in D. discoideum.     

Endotoxin-induced lung injury in rats: role of eicosanoids

We studied lung vascular injury and quantitated lung eicosanoids in rats after intraperitoneal injection of Salmonella enteritidis endotoxin. Within 40 min after endotoxin injection (20 mg/kg), lung tissue thromboxane B2 doubled, although 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) increased by 8- to 10-fold. Lung 5-hydroxyeicosatetraenoic acid and leukotriene C4 were variably increased by endotoxin. The levels of all eicosanoids returned to base line 6 h after endotoxin challenge. Lung vascular injury, as assessed by the extravascular accumulation of 125I-albumin and water in isolated perfused lungs, was observed 90 min after endotoxin injection (0.02-20 mg/kg) in vivo. Inhibition of the cyclooxygenase pathway with indomethacin and the lipoxygenase pathway with diethylcarbamazine and 2-(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoqui none failed to attenuate endotoxin-induced lung injury. In addition, essential fatty acid deficiency, which markedly reduced lung tissue levels of 6-keto-PGF1 alpha, thromboxane B2, and leukotriene C4, did not protect against endotoxin injury. We conclude that although lung eicosanoids are activated during endotoxemia, they do not play a crucial role in the development of acute lung vascular injury in rats.     

Additive effects of clofibric acid and pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) deficiency on hepatic steatosis in mice fed a high saturated fat diet

Although improving glucose metabolism by inhibition of pyruvate dehydrogenase kinase 4 (PDK4) may prove beneficial in the treatment of type 2 diabetes or diet-induced obesity, it may have detrimental effects by inhibiting fatty acid oxidation. Peroxisome proliferator-activated receptor α (PPARα) agonists are often used to treat dyslipidemia in patients, especially in type 2 diabetes. Combinational treatment using a PDK4 inhibitor and PPARα agonists may prove beneficial. However, PPARα agonists may be less effective in the presence of a PDK4 inhibitor because PPARα agonists induce PDK4 expression. In the present study, the effects of clofibric acid, a PPARα agonist, on blood and liver lipids were determined in wild-type and PDK4 knockout mice fed a high-fat diet. As expected, treatment of wild-type mice with clofibric acid resulted in less body weight gain, smaller epididymal fat pads, greater insulin sensitivity, and lower levels of serum and liver triacylglycerol. Surprisingly, rather than decreasing the effectiveness of clofibric acid, PDK4 deficiency enhanced the beneficial effects of clofibric acid on hepatic steatosis, reduced blood glucose levels, and did not prevent the positive effects of clofibric acid on serum triacylglycerols and free fatty acids. The metabolic effects of clofibric acid are therefore independent of the induction of PDK4 expression. The additive beneficial effects on hepatic steatosis may be due to induction of increased capacity for fatty acid oxidation and partial uncoupling of oxidative phosphorylation by clofibric acid, and a reduction in the capacity for fatty acid synthesis as a result of PDK4 deficiency.     

The time-course development of the effects of ethanol ingestion on choline oxidase

Male rats were fed a low-fat diet containing 36% of calories as ethanol, and the time-course development of the effects of ethanol on liver mitochondrial oxidation of choline was determined. Ethanol induced an increase in choline oxidase at days 2, 5 and 7 after being introduced into the diet. Due to an observed 32% increase in total fatty acids in the whole liver, defatted bovine serum albumin was added to the buffer used to homogenize the liver. The presence of bovine serum albumim resulted in a significant decrease in choline oxidase activity at days 2 and 5; however, ethanol still induced an increase in choline oxidase activity in these mitochondria. The total fatty acid concentration of mitochondria prepared in the absence of bovine serum albumin increased steadily until day 5; however, by day 7 the fatty acid concentration had returned to control levels. The addition of bovine serum albumin to the homogenization medium prevented the increase in the total amount of fatty acids. The fatty acid composition of the bovine serum albumin-treated mitochondria, however, was not different from the mitochondria is isolated in the absence of bovine serum albumin. Further, the addition of a free fatty acid to isolated mitochondrial preparations caused about a 100% increase in choline oxidase. These data are consistent with the idea that choline oxidase may be regulated to some extent by an influx or an increase in free fatty acids in the liver as a result of ethanol ingestion. Thus, a second mechanism has been described which contributes to the increase in choline oxidase after ethanol ingestion.     

Essential fatty acids in the fetal and newborn lamb

The concentrations of linoleic and linolenic acids and their metabolites in the liver, kidney, brain, erythrocytes and plasma of fetal lambs at various stages of gestation, and of newborn and 2-week-old suckled lambs was determined. Throughout gestation the fetal tissues, erythrocytes and plasma all contained low levels of linoleic and linolenic acids together with consistently high levels of their long-chain polyunsaturated metabolites. The triene: tetraene (eicosa-5,8,11-trienoic acid/arachidonic acid) ratio was always 0.4 or less except at birth when it reached 0.6 in liver and 0.9 in plasma. Milk intake significantly increased the linoleic and linolenic acid levels in the lamb by 2 weeks after birth. These results show that the developing fetal lamb should not be regarded as being deficient in essential fatty acids, as suggested by previous investigators. It is proposed that the total metabolites of linoleic and linolenic acids are the most appropriate measure of the essential fatty acid status of the fetal lamb.     

Dietary myristic acid at physiologically relevant levels increases the tissue content of C20:5 n-3 and C20:3 n-6 in the rat

This study was designed to investigate the effect of myristic acid on the biosynthesis and metabolism of highly unsaturated fatty acids, when it is supplied in a narrow physiological range in the diet of the rat (0.2-1.2% of total dietary energy). Three experimental diets were designed, containing 22% of total dietary energy as lipids and increasing doses of myristic acid (0.71, 3.00 and 5.57% of total fatty acids). Saturated fat did not exceed 31% of total fat and the C18:3 n-3 amount in each diet was strictly equal (1.6% of total fatty acids). After 7 weeks, the diets had no effect on plasma cholesterol level but greatly modified the liver, plasma and adipose tissue saturated, monounsaturated and polyunsaturated fatty acid profiles. Firstly, daily intakes of myristic acid resulted in a dose-dependent tissue accumulation of myristic acid itself. Palmitic acid was significantly increased in the tissues of the rats fed the higher dose of myristic acid. A dose-response accumulation of tissue C16:1 n-7 as a function of dietary C14:0 was also shown. Secondly, a main finding was that, among n-3 and n-6 polyunsaturated fatty acids, a dose-response accumulation of liver and plasma C20:5 n-3 and C20:3 n-6 (two precursors of eicosanoids) as a function of dietary C14:0 was shown. This result suggests that dietary myristic acid may participate in the regulation of highly unsaturated fatty acid biosynthesis and metabolism.     

Can muscle fatty acid signature be used to distinguish diets during the marine trophic phase of sea lamprey (Petromyzon marinus, L.)?

Characterization of muscle and liver fatty acid profiles, determination of liver lipogenic and lipolytic activities and estimation of liver fatty elongases and desaturases activities of sea lamprey were realized at the beginning of the spawning migration. The muscle fatty acid profile was consistent with the location of capture, and revealed that animals captured far upstream from the river mouth presented the lowest C18:1ω9 levels and the highest relative proportions of C20:4ω6, C20:5ω3 (EPA), C22:5ω3 (DPA) and C22:6ω3 (DHA). These results suggest: (i) the vital importance of the conservation of C20:4ω6 as a precursor of eicosanoids; (ii) the retention of EPA, DPA and DHA for metabolic energy for reproduction; and (iii) the utilization of C18:1ω9 for metabolic fuel use in the beginning of the spawning period. Hepatic lipolysis and lipogenesis revealed significant differences which could, eventually, result from the diet during the parasitic phase of sea lamprey life cycle. Present results revealed that the muscle act as a fat depot site which explains the few significant correlations observed for fatty acids between muscle and liver. Muscle neutral lipids fatty acid signature at the beginning of the spawning migration can be used to distinguish differences in the diet of sea lampreys during the marine trophic phase of their life cycle.     

Dietary lipid modification of renal disorders and ether phospholipid metabolism.

The formation of arachidonic acid derived eicosanoids, including thromboxane A2 and leukotriene B4, as well as platelet-activating factor (1-O-alkyl-2-acetyl-glycerophosphocholine), has been implicated in various renal pathophysiologies. Alteration of the fatty acid composition of membrane phospholipids in platelets, the glomerulus, and inflammatory cells, and of 1-O-alkyl-2-acyl-glycerophosphocholine (platelet-activating factor precursor) can be attained by dietary lipid modifications (e.g., consumption of fish oil containing n - 3 polyunsaturated fatty acids). These changes have been associated with an attenuation in renal disease progression and modifications in the synthesis and actions-interactions of eicosanoids, cytokines, and platelet-activating factors.