Lifelong exposure to dietary fish oil alters macrophage responses in Walker 256 tumor-bearing rats

Supplementation of the diet with fish oil (FO) decreases growth of the Walker 256 tumor and decreases the cachexia associated with tumor-bearing. The mechanisms by which FO inhibits tumor growth and cachexia are unknown. Macrophages are very important in host defence against tumors since they produce several anti-tumor agents which in turn have been shown to be modified by dietary FO, but rarely in the setting of tumor bearing and never in relation to lifelong exposure. In this study, we compared the effects of supplementation of the diet of pregnant and lactating rats and subsequent supplementation of the offspring with coconut fat or FO on macrophage activities involved in anti-tumor defence. FO supplementation was able to induce an increase in phagocytosis, in O2-, H2O2, nitric oxide, and TNF-alpha production by macrophages and in lysosomal volume in non-tumor-bearing rats. However, phagocytosis, production of O2- and H2O2 and lysosomal volume were not affected by the FO diet when rats were bearing tumors, although nitric oxide production was higher in these animals. It appears that tumor bearing activates the innate immune system and that dietary FO has little effect on innate immunity in the presence of Walker 256 tumors. Thus, it is still unclear how FO decreases the growth of Walker 256 tumors and the associated cachexia.     

Decreased tumor growth in Walker 256 tumor-bearing rats chronically supplemented with fish oil involves COX-2 and PGE2 reduction associated with apoptosis and increased peroxidation

Many studies have shown that addition of fish oil (FO) to the diet reduces tumor growth but the mechanism(s) of action involved is (are) still unknown. In this study, we examine some possible mechanisms in tumor-bearing rats chronically supplemented with FO. Male Wistar rats (21 days old) were fed with regular chow and supplemented with coconut or FO (1g/kg body weight) until they reached 70 days of age. Then, they were inoculated with a suspension of Walker 256 ascitic tumor cells (2 x 10(7)ml) and after 14 days they were killed. Supplementation with FO resulted in significantly lower tumor weight, greater tumor cell apoptosis, lower ex vivo tumor cell proliferation, a higher tumor content of lipid peroxides, lower expression of cyclooxygenase-2 (COX-2) in tumor tissue and a lower plasma concentration of prostaglandin E2 than observed in rats fed regular chow or supplemented with coconut oil. These results suggest that reduction of tumor growth by FO involves an increase in apoptosis and of lipid peroxidation in tumor tissue, with a reduction in tumor cell proliferation ex vivo, COX-2 expression and PGE2 production. Thus, FO may act simultaneously through multiple effects to reduce tumor growth. Whether these effects are connected through a single underlying mechanism remains to be seen.     

Fish oil supplementation in F1 generation associated with naproxen, clenbuterol, and insulin administration reduce tumor growth and cachexia in Walker 256 tumor-bearing rats

Weanling female Wistar rats were supplemented with fish oil (1 g/kg body weight) for one generation. The male offspring received the same supplementation until to adult age. Rats supplemented with coconut fat were used as reference. Some rats were inoculated subcutaneously with a suspension (2 x 10(7) cells/mL) of Walker 256 tumor. At day 3, when the tumor was palpable, rats were treated with naproxen (N) (0.1 mg/mL), clenbuterol (Cb) (0.15 mg/kg body weight), and insulin (I) (10 U/kg body weight). At day 14 after tumor inoculation, the animals were killed. Tumor was removed and weighed. Blood, liver, and skeletal muscles were also collected for measurements of metabolites and insulin. In both tumor-bearing untreated rats and tumor-bearing rats supplemented with coconut fat, tumor growth, triacylglycerol, and blood lactate levels were higher, and glycogen content of the liver, blood glucose, cholesterol and HDL-cholesterol levels were lower as compared with the non-tumor-bearing and fish oil supplemented groups. Fish oil supplementation of tumor-bearing rats led to a partial recovery of the glycogen content in the liver and a full reversion of blood glucose, lactate, cholesterol, and HDL-cholesterol levels. The treatment with N plus Cb plus I attenuated cancer cachexia and decreased tumor growth in both coconut fat and fish oil supplemented rats. In conclusion, chronic fish oil supplementation decreased tumor growth and partially recovered cachexia. This beneficial effect of fish oil supplementation was potentiated by treatment with naproxen plus clenbuterol plus insulin.     

Testicular morphometry of rats with Walker 256 tumor supplemented with L-glutamine

Glutamine is often used to treat metabolic changes associated with anorexia-cachexia syndrome in patients with malignant neoplasms. Walker 256 tumor is an excellent model for studying these changes associated with cancer in different organs, including injuries in testicular functions. However, the effects of supplementing glutamine on testicular morphometry in this model have not yet been investigated. Thus, the objective of this study was to evaluate the effect of L-glutamine supplementation on testicular morphometry in rats transplanted with Walker 256 tumor cells. Forty puberty Wistar rats were divided into four groups: control without L-glutamine (C); control supplemented with L-glutamine (CG); inoculated with Walker 256 tumor cells (WT) and inoculated with Walker 256 tumor cells and supplemented with L-glutamine (WTG). The testicles were removed, weighed, fixed in Bouin, and included in paraffin for histomorphometric analysis. Walker 256 tumor caused quantitative changes in the tubular and intertubular compartments and tunica albuginea, with reductions in the percentages of lumen and tunica albuginea, number of Sertoli cells per gram of testis; number of Leydig cells; percentage of blood vessels and connective tissue in intertubule. However, glutamine supplementation prevented part of these changes caused by the tumor, presenting mainly a protective effect on the tunica albuginea and percentage of blood and lymph vessels in the intertubule. These results indicate the potential of L-glutamine was able to recover for testicular dysfunction associated with cancer.     

The antidepressant role of dietary long-chain polyunsaturated n-3 fatty acids in two phases in the developing brain

In this work we investigated the effect from fish oil (FO) supplementation, rich in n-3 fatty acids, on an antidepressant effect on adult rats in Phase A (supplementation during pregnancy and lactation) and phase B (supplementation during post-weaning until adulthood). During Phase A, female rats, used as matrix to obtain male rats, were divided in three groups: FO (daily supplemented), CF (coconut fat daily supplemented) and control (not supplemented). Our results showed that adult rats whose mothers were supplemented with FO during Phase A and rats supplemented during phase B demonstrated a significantly decreased immobility time when compared to control and CF groups. There was no difference in neither motor activity nor anxiety behavior in the three groups excluding false positive results. Our results suggest that n-3 fatty acids supplementation during Phases A and B had a beneficial effect on preventing the development of depression-like behavior in adult rats.     

Effect of a high-intensity exercise training on the metabolism and function of macrophages and lymphocytes of walker 256 tumor bearing rats

Epidemiologic studies suggest that moderately intense training promotes augmented immune function, whereas strenuous exercise can cause immunosupression. Because the combat of cancer requires high immune function, high-intensity exercise could negatively affect the host organism; however, despite the epidemiologic data, there is a lack of experimental evidence to show that high-intensity training is harmful to the immune system. Therefore, we tested the influence of high-intensity treadmill training (10 weeks, 5 days/week, 30 mins/day, 85% VO(2)max) on immune system function and tumor development in Walker 256 tumor-bearing Wistar rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, in addition to some functional parameters such as hydrogen peroxide production, phagocytosis, and lymphocyte proliferative responses. The metabolism of Walker 256 cells was also investigated. Results demonstrated that high-intensity training increased the life span of tumor-bearing rats, promoted a reduction in tumor mass, and prevented indicators of cachexia. Several changes, such as a reduction in body weight and food intake and activation of glutamine metabolism in macrophages and lymphocytes induced by the presence of Walker 256 tumor, were prevented by high intensity training. The reduction in tumor growth was associated with an impairment of tumor cell glucose and glutamine metabolism. These data suggest that high-intensity exercise training may be a viable strategy against tumors.     

Regulation of lactate production and utilization in rat tumors in vivo

These experiments were performed to determine the factor(s) that regulate lactic acid production and utilization by rat tumors in vivo. Arteriovenous differences for glucose and lactic, pyruvic, 3-OH-butyric, and acetoacetic acids were measured across "tissue-isolated" Walker 256 sarcocarcinomas and Morris 5123C hepatomas in fasted rats anesthetized with sodium pentobarbital. Twenty-six per cent of the sarcocarcinomas (n = 53) and 48% of the hepatomas (n = 29) utilized blood lactic acid. The remainder released lactic acid into the venous blood. The steady-state rate of glucose consumption was similar in both lactate-producing and lactate-utilizing tumors. The range of lactate concentrations in the blood leaving the tumors was narrower than the range of lactate concentrations in the blood entering the tumors. This difference was caused by tumor lactic acid production at low arterial lactate concentrations and tumor lactic acid utilization at high arterial lactate concentrations. Individual tumors changed from lactic acid production to lactic acid utilization in a matter of minutes in response to an increase in the arterial lactic acid concentration. Mean lactic plus pyruvic acid concentrations and lactic/pyruvic acid ratios in the tumor venous blood were 2.15 +/- 0.22 and 23.4 +/- 3.7 mM, respectively, for Walker sarcocarcinoma 256 (n = 18) and 1.28 +/- 0.13 and 48.1 +/- 5.1 mM, respectively, for hepatoma 5123C (n = 11). The results suggest: that a steady-state lactic plus pyruvic acid concentration and lactic/pyruvic acid ratio are maintained in the tumor cell cytoplasm by the active glycolytic pathway and by lactic acid dehydrogenase; that the tumor intracellular concentrations equilibrate with the arterial blood and that the tumor steady state is expressed in the tumor venous blood; and that tumor lactic acid production or utilization results from the equilibration between the variable arterial lactic acid concentration and the more constant tumor intracellular steady-state lactic acid concentration. Since the arterial lactate concentration may be less than, greater than, or equal to the intracellular steady-state concentration, an individual tumor may produce, utilize or neither produce nor utilize lactic acid.     

Production of cachexia mediators by Walker 256 cells from ascitic tumors

In neoplasic cachexia, chemical mediators seem to act as initiators or perpetuators of this process. Walker 256 cells, whose metabolic properties have so far been little studied with respect to cancer cachexia, are used as a model for the study of this syndrome. The main objective of this research was to pinpoint the substances secreted by these cells that may contribute to the progression of the cachectic state. Since inflammatory mediators seem to be involved in the manifestation of this syndrome, the in vitro production of nitric oxide (NO), cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)), and prostaglandin E2 (PGE2) was evaluated in Walker 256 cells isolated from ascitic tumors. After 4 or 5 h, a significant increase in NO production was observed (2.55 +/- 1.56 and 4.05 +/- 1.99 nmol NO per 10(7) cells, respectively). When isolated from a 6-day-old tumor, a significantly lower production of IL-6 and higher production of TNF-alpha than in cells from a 4-day-old tumor were observed, indicating a relationship between the production of cytokines and the time of tumor development after implantation. Considerable production of PGE(2) by Walker 256 cells isolated from the 6-day-old tumor was also observed. Polyamines were also determined in Walker 256 cells. Levels of putrescine, spermidine, and spermine did not show significant differences in tumors developed during 4 or 6 days. Direct evidence of the release of proinflammatory cytokines and PGE2 by Walker 256 cells suggests that these mediators can drive the cachectic syndrome in the host, the effect being dependent on tumor development time.     

Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells

In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages and on macrophage-mediated cytotoxicity towards L929 and P815 cells were investigated. C57Bl6 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the principal fat source. The fatty acid composition of the macrophages was markedly influenced by that of the diet fed. Lipopolysaccharide (LPS)-stimulated macrophages from FO-fed mice showed significantly lower production (up to 80%) of PGE2 than those from mice fed on each of the other diets. There was a significant positive linear correlation between the proportion of arachidonic acid in macrophage lipids and the ability of macrophages, to produce PGE2. Lipopolysaccharide-stimulated TNF-alpha production by macrophages decreased with increasing unsaturated fatty acid content of the diet (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed significantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macrophages from mice fed on the LF diet. Macrophages from FO-fed mice showed significantly higher production of nitrite than those from mice fed on the OO and SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO diets significantly decreased macrophage- mediated killing of P815 cells (killed by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compared with feeding the LF diet, feeding the OO or SO diets significantly decreased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oil or FO feeding did not alter killing of L929 cells by macrophages, compared with feeding the LF diet. It is concluded that the type of fat in the diet affects macrophage composition and alters the ability of macrophages to produce cytotoxic and immunoregulatory mediators and to kill target tumour cells.     

Dietary supplementation with Pluronic L-81 modifies hepatic secretion of very low density lipoproteins in the rat

Supplementation of high fat/cholesterol-enriched diets with polyoxypropylene-polyoxyethylene copolymers containing 90% hydrophobic constituents has been found to impair enteric secretion of chylomicrons, lower plasma levels of very low density (VLDL) and low density (LDL) lipoprotein cholesterol and prevent diet-induced hypercholesterolemia and atherosclerosis. These agents are known to be absorbed from the gastrointestinal tract and excreted in bile. In order to determine whether dietary supplementation with this group of hydrophobic poloxalenes influences hepatic secretion of triglyceride-rich lipoproteins, groups of rats were maintained for 21-34 days on either standard chow, semisynthetic diet containing 10.0% safflower oil/1.0% cholesterol, or each of the above diets supplemented with the hydrophobic poloxalene Pluronic L-81. At the end of the feeding period, newly secreted hepatic VLDL were isolated from 2-hr recirculating liver perfusates, quantitated, and characterized. Compared to perfusions in chow-fed rats, perfusion experiments in rats fed the high fat/cholesterol-enriched semisynthetic diet revealed a 3.1-fold increased net hepatic VLDL secretion rate; enrichment of secretory VLDL in cholesteryl esters and in C18:2 core lipid fatty acids; and a shift in the size distribution of secretory VLDL towards larger particles. When the 0.5% Pluronic L-81 was included in the high fat/cholesterol-enriched semisynthetic diet, the net hepatic VLDL secretion rate fell significantly and the physicochemical properties of secretory VLDL in these rats were found to resemble those of chow-fed animals. Supplementation of the chow diet with L-81 resulted in a significant fall in the net hepatic VLDL secretion rate from that observed in rats fed chow alone. Compared to rats fed chow alone, perfusate VLDL from rats fed each of the other experimental diets contained markedly lower amounts of both apoB molecular weight variants, as analyzed by gradient gel electrophoresis and densitometric gel scanning. Since previous studies have demonstrated that VLDL are the major cholesterol transport lipoproteins following fat/cholesterol feeding; a precursor-product relationship exists between fat/cholesterol-induced hepatic VLDL and plasma VLDL; such particles are capable of delivering cholesterol to the arterial wall; and dietary supplementation with hydrophobic poloxalenes prevents both the increase in plasma VLDL-cholesterol and diet-induced atherosclerosis, it is possible that dietary supplementation with hydrophobic poloxalenes may influence the atherogenic process through direct and/or indirect effects on hepatic VLDL transport.     

Prolactin and growth hormone synthesis and thymidine incorporation in dissociated rat pituitary tumor cells

The effect of in vivo diethylstilbestrol (DES) treatment on the MtT/W15 transplantable pituitary tumor was examined in dissociated pituitary cells by measuring the rate of incorporation of [3H]thymidine into DNA and the synthesis of prolactin (PRL) and growth hormone (GH) as assessed by the rate of incorporation of [3H]leucine. MtT/W15 transplantable pituitary tumors from rats treated for 3 weeks with DES showed significant reduction in the extent of [3H]thymidine incorporation compared with tumor cells from untreated rats (2231 +/- 182 vs 172 +/- 17 dpm/10(5) cells; n = 3). In addition, tumor cells from DES-treated rats showed a significant increase in GH synthesis compared with tumor cells from untreated rats. In contrast to these findings, dissociated pituitary cells from non-tumor-bearing rats given 10 mg DES in Silastic tubing for 3 weeks showed a three-fold increase in PRL synthesis compared to cells from untreated control rats (29.3 +/- 1.5 vs 10.0 +/- 0.9% of total radioactivity in gel; n = 3. There was also a four-fold increase in the rate of [3H]thymidine incorporation after DES-treatment in non-tumor-bearing rats (695 +/- 114 vs 178 +/- 13.9 dpm/10(5) cells; n = 3). These results indicate that DES inhibits MtT/W15 pituitary tumor cell proliferation, while stimulating synthesis of GH.     

Insulin treatment can abolish changes in glucose and glutamine metabolism of lymphocytes and macrophages caused by the implantation of the walker 256 tumour

Activation of lymphocytes and macrophages by the implantation of tumour cells (10⁷ cells per rat) into the left flank of rats increased the conversion of glucose to lactate and of glutamine to glutamate and aspartate and the decarboxylation of [U-¹⁴C]-glucose and [U-¹⁴C]-glutamine in incubated cells. In addition, the amount of GLUT1 was increased in macrophages. The effect of insulin treatment on glucose and glutamine metabolism of lymphocytes and macrophages activated by Walker 256 tumour implantation was also examined. For this purpose, insulin was injected subcutaneously (4 U/100 g b.w. daily) after the fourth day of tumour implantation and the rats were killed 10 days afterwards. Insulin treatment fully reverted the changes due to tumour implantation in the metabolism of glucose and glutamine in lymphocytes and of glucose in macrophages.     

Biological significance of phosphorylation and myristoylation in the regulation of cardiac muscle proteins

The effect of different dietary fats on peritoneal macrophage plasma membrane fluidity, intracellular cyclic AMP (cAMP) production, GTP hydrolysis and TNF binding and TNF-induced IL1 and IL6 production was investigated. After a four week period, fluidity, as determined by both fluorescence recovery after photobleaching (FRAP) and anisotropy was lowest and highest in animals fed corn and fish oil respectively. After eight weeks feeding, lateral membrane movements were decreased substantially in fish, olive and coconut oil fed dietary groups, whereas an increase in the corn oil fed group was observed, no effect was observed in macrophages from the butter fed group. However, an increase in the packing was observed in macrophages from all dietary groups except in the olive oil fed group. GTPase values for the coconut oil and butter groups were higher than in any other dietary group. After receiving the diet for 8 weeks these differences between the groups were no longer apparent. Exposure of macrophages to TNF had no effect on the rate of GTP hydrolysis. A major enhancement of cAMP production became apparent between weeks 4 and 8 of dietary treatment. After 4 weeks on the diet, values were significantly higher from cells of animals fed corn and olive oils than from animals fed fish oil. After 8 weeks, while there was a general enhancement of production, further differences became apparent. Feeding corn and coconut oils resulted in the highest values and olive oil and chow in the lowest. It is proposed that fats rich in n-3 fatty acids (fish oils) alter membrane fluidity, decrease TNF binding affinity, GTPase activity and cAMP production which appears not to modify cytokine production after short term dietary supplementation. However, after long term feeding it appears that increases in the sensitivity of the TNF receptors plays a major role in modifying cytokine production. (Mol Cell Biochem 166: 135-143, 1997)     

Perinatal polyunstaurated fatty acids supplementation causes alterations in fuel homeostasis in adult male rats but does not offer resistance against STZ-induced diabetes

Maternal factors can have major imprinting effects on homeostatic mechanisms in the developing fetus and newborn. Here we studied whether supplemented perinatal polyunsaturated fatty acids (PUFAs) influence energy balance and fuel homeostasis later in life. Between day 10 after conception and day 10 after delivery, female rats were subjected to chow enriched with 10% fish-oil (FO-rich). Fish oil contains high concentrations of n-3 biosynthesis endpoint products, which may have caused the increased membrane phospholipid incorporation (particularly derived from the long-chain 20?+:n-3 PUFAs) in 10-day old pup brains. Adult male offspring of FO-rich fed rats had reduced body weight (-?20%) at 3 months, and had lower levels of plasma leptin (-?54%), insulin (-?41%), triglycerides (-?65%), and lactate (-?46%) than controls. All differences between groups were lost 48?h after streptozotocin (STZ) treatment. At 4.5 months of age, body weights of FO-rich were still lower (-?6%) than controls, but were associated with increased food intake, and increased insulin sensitivity (following intraperitoneal injection) to lower blood glucose levels relative to controls. We concluded that perinatal FO supplementation has lasting effects on body weight homeostasis and fuel metabolism in male offspring, but does not offer resistance against STZ-induced diabetes.     

Influence of co-administration of oral insulin and docosahexaenoic acid in mice

Insulin and docosahexaenoic acid are both present in human milk. The aim of this study was to examine the effect of co-administration of oral insulin and DHA in mice. Immediately after weaning, Balb C mice were divided into four groups of seven mice each for a period of 4 weeks. Group 1 received a chow diet only. Group 2 received a chow diet and also was given human insulin (1 unit/mL of drinking water) without docosahexaenoic acid. Group 3 received a chow diet supplemented with docosahexaenoic acid (500 mg/kg/day in the chow) and no insulin. Group 4 received a chow diet and supplementation with both human insulin and docosahexaenoic acid. At 28 days, fasting blood levels of glucose, insulin, lipids, lipid peroxidation analysis, docosahexaenoic acid plasma levels, and docosahexaenoic acid content in red blood cells were determined. We found that glucose levels were lower in the group that was supplemented with insulin only (group 2, 61.4 mg/dL +/- 2.8,mean +/- SD) and in the group that was supplemented with DHA only (group 3, 61.1 mg/dL +/- 2.0) compared to controls (group 1, 71 mg/dL +/- 6.9, P < 0.0001). Supplementation of both insulin and docosahexaenoic acid (group 4) resulted in significantly lower glucose levels (56.4 mg/dL +/- 2.6) compared to those in groups 2 and 3 (P < 0.01). No significant differences were found in lipid profile or lipid peroxidation between the groups. We conclude that adding insulin or docosahexaenoic acid to the diet of weaned Balb C mice reduces glucose blood levels. Supplementation with both substances has a synergistic effect. The presence of insulin and docosahexaenoic acid in human milk may be the cause for reduced glucose levels in breast-fed infants, in addition to the known effects of DHA on insulin sensitivity.     

Dietary fish oil modulation of macrophage amyloid P component responses in mice

Arthritis-susceptible B10.RIII mice, maintained on either fish oil (FO) or corn oil (CO) diets (5% by weight), and amyloid-susceptible CBA/J mice fed chow diets were given 20 micrograms purified LPS by i.p. injection. Both strains of mice responded to LPS with a 20- to 30-fold increase in plasma amyloid P component (AP) levels. There were no differences in the response between males and females or between FO and CO treatment groups. The data demonstrated that cultured peritoneal macrophages (M phi) respond to LPS stimulation with increased secretion of AP. In contrast to plasma AP levels, the MO response to LPS stimulation, as measured by production of AP, was influenced by both gender and diet. Although M phi from both male and female mice on the CO diet and male mice on the FO diet responded similarly, those from female mice on the FO diet secreted only 25 to 35% as much AP as did the other three groups. There were no dietary effects on the LPS-induced serum amyloid A protein response nor was there detectable serum amyloid A protein produced by the M phi. These results demonstrate that unstimulated, resident peritoneal M phi secrete AP as a normal constituent and in increasing amounts in response to LPS stimulation.     

Arachidonic acid and linoleic acid supplementation increase prostanoid production in rats fed a butter-enriched diet

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks and then supplemented orally with either 90 mg of ethyl arachidonate or ethyl linoleate daily for 2 weeks. For comparative reasons, one group of animals was fed standard laboratory rat chow for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. When compared to butter-fed rats, aortic PGI2 production, collagen-induced platelet aggregation and TXA2 production were significantly increased in rats supplemented with ethyl arachidonate to levels similar to those seen in chow-fed rats. Ethyl linoleate supplementation also tended to increase aortic PGI2 production, collagen-induced platelet aggregation and TXA2, but not to the same extent. These changes were accompanied by increases in the level of arachidonic acid and linoleic acid in aortic and plasma PL and a decrease in the level of eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA). These data indicate that supplementation with small doses of preformed arachidonic acid was more effective than supplementation with its precursor, linoleic acid, in reversing the effects on prostanoid production and phospholipid fatty acid composition in rats fed diets enriched with butter.     

Glucose and glutamine metabolism in rat macrophages: enhanced glycolysis and unaltered glutaminolysis in spontaneously diabetic BB rats.

Metabolism of glutamine (Gln, 2 mM) and glucose (5 mM) was studied in vitro in isolated resident peritoneal macrophages from both normal (BBn) and spontaneously diabetic BB (BBd) rats. The major products from Gln were ammonia, glutamate, CO2 and to a lesser extent aspartate. Glucose decreased (P less than 0.01) the production of ammonia, CO2 and aspartate from Gln by 34-60%, but had no effect on the amount of glutamate accumulated. The major products from glucose were lactate and to a much lesser extent pyruvate and CO2. Gln decreased (P less than 0.01) 14CO2 production from [U-14C]glucose by 19-28%, increased (P less than 0.01) pyruvate production by 35-49%, but had no effect on lactate production. The fraction of glucose metabolized via the pentose phosphate pathway (PC) was less than 5%. There were no significant differences in Gln metabolism between BBn and BBd macrophages. The production of lactate and pyruvate and the flux from glucose into the PC were increased (P less than 0.01) by 2.4, 1.8 and 1.5-fold, respectively, in BBd cells. Increased macrophage glucose metabolism was also observed in diabetes-prone BB (BBdp) rats at 75-80 days but not at 50 days of age. In the presence of both Gln and glucose, potential ATP production from glucose was 2- and 4-times that from Gln, respectively, in BBn and BBd cells. Lactate production was the major pathway for glucose-derived ATP generation. These results demonstrate (a) glycolysis and flux from glucose through the pentose phosphate pathway are enhanced with no alteration in glutaminolysis in BBd macrophages; and (b) glucose may be a more important fuel than Gln for macrophages, particularly in BBd rats. The increased glucose metabolism may be associated with functional activation of the macrophages that have been proposed to be involved in beta-cell destruction and the development of diabetes.     

Proposed mechanisms for red palm oil induced cardioprotection in a model of hyperlipidaemia in the rat

High-cholesterol diets alter myocardial and vascular NO-cGMP signaling and have been implicated in ischaemic/reperfusion injury. We investigated the effects of dietary red palm oil (RPO) containing fatty acids, carotonoids, tocopherols and tocotrienols on myocardial ischaemic tolerance and NO-cGMP pathway function in the rat. Wistar rats were fed a standard rat chow+/-RPO, or a standard rat chow+cholesterol+/-RPO diet. Myocardial mechanical function and NO-cGMP signaling pathway intermediates were determined before, during and after 25 min ischaemia. RPO-supplementation improved aortic output recovery and increased myocardial ischaemic cGMP concentrations. Simulated ischaemia (hypoxia) increased cardiomyocyte nitric oxide levels in the two RPO supplemented groups, but not in control non-supplemented groups. RPO supplementation also increased hypoxic nitric oxide levels in the control diet fed, but not the cholesterol fed rats. These data suggest that dietary RPO may improve myocardial ischaemic tolerance by increasing bioavailability of NO and improving NO-cGMP signaling in the heart.     

不同脂肪源对异育银鲫的生长、体组成和肌肉脂肪酸的影响

配制了十种等氮等能的饲料饲喂3.53 g的异育银鲫幼鱼12周, 探讨异育银鲫对不同脂肪源的利用效果。十种饲料中分别添加8%的鱼油(FO)、椰子油(CNO)、玉米油(CO)、亚麻油(LO)、大豆油(SO)、菜籽油(RO)、1∶1鱼油-椰子油(FCNO)、1∶1鱼油-玉米油(FCO)、1∶1鱼油-亚麻油(FLO)和1∶1∶1∶1鱼油-椰子油-玉米油-亚麻油混合油(MIX)。每组饲料三个平行, 每个平行30尾。实验在循环水养殖系统中进行, 水温控制在(241)℃。结果表明, 在单一脂肪源中, 豆油组和椰子油组的增重率最高, 其次是菜籽油组, 鱼油、玉米油和亚麻油组的增重率最低。与相应的单一脂肪源相比, 饲料中鱼油与椰子油、玉米油或亚麻油1∶1混合后使用提高了异育银鲫的生长。摄食不同脂肪源饲料的异育银鲫血清生化指标、各组织的水分和脂肪含量差异不明显(P0.05)。肌肉脂肪酸与饲料脂肪源呈明显正相关。摄食豆油和菜籽油饲料的鱼体肌肉中20:4n-6较高, 而摄食亚麻油饲料的鱼则含有较高的20:5n-3和22:6n-3, 表明异育银鲫具有转化18:2n-6和 18:3n-3为高不饱和脂肪酸的能力。从实验可以看出, 豆油、椰子油和菜籽油是异育银鲫饲料中良好的脂肪源。