Diet deficient in alpha-linolenic acid alters fatty acid composition and enzymatic properties of Na+, K+-ATPase isoenzymes of brain membranes in the adult rat

The effects of dietary (n-6)/(n-3) polyunsaturated fatty acid balance on fatty acid composition, ouabain inhibition, and Na(+) dependence of Na(+), K(+)-ATPase isoenzymes of whole brain membranes were studied in 60-day-old rats fed over two generations a diet either devoid of alpha-linolenic acid [18:3(n-3)] (sunflower oil diet) or rich in 18:3(n-3) (soybean oil diet). In the brain membranes, the sunflower oil diet led to a dramatic decrease in docosahexaenoic acid [22:6(n-3)] membrane content. The activities of Na(+), K(+)-ATPase isoenzymes were discriminated on the basis of their differential affinities for ouabain and their sensitivity to sodium concentration. The ouabain titration curve of Na(+), K(+)-ATPase activity displayed three inhibitory processes with markedly different affinity [i.e., low (alpha1), high (alpha2), and very high (alpha3)] for brain membranes of rats fed the sunflower oil diet, whereas the brain membranes of rats fed the soybean oil diet exhibited only two inhibitory processes, low (alpha1) and high (alpha2' = alpha2 + alpha3). Regardless of the diet, on the basis of the Na(+) dependence of Na(+), K(+)-ATPase activity, three isoenzymes were found: alpha1 form displaying an affinity 1.5- to 2-fold higher that of than alpha2 and 3-fold higher that of alpha3. In rats fed the sunflower oil diet, alpha2 isoenzyme exhibited higher affinity for sodium (Ka = 8.8 mmol/L) than that of rats fed the soybean oil diet (Ka = 11.7 mmol/L). These results suggest that the membrane lipid environment modulates the functional properties of Na(+), K(+)-ATPase isoenzymes of high ouabain affinity (alpha2).     

Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks.

Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet-induced lowering of high levels of 22:6(n-3).     

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Background

Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.

Methodology/Principal Findings

We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.

Conclusions/Significance

The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.     

In vivo formation of metabolites of prostaglandins I2 and I3 in the marmoset monkey (Callithrix jacchus) following dietary supplementation with tuna fish oil

Recent studies have shown that ingestion of eicosapentaenoic acid (EPA) in man results in the formation of 'trienoic' prostanoids which amy partly explain the potent antithrombotic/antiatherogenic properties of long-chain polyunsaturated n-3 fatty acids (PUFAs). However, endogenous formation of cyclooxygenase metabolites of EPA has not been demonstrated in an animal model, and in vitro studies indicate a clear species difference in the conversion of EPA to PGI3. Thus, in the present study, the in vivo formation of PGI3 following long-term dietary tuna fish oil supplementation was investigated in a small non-human primate - the marmoset monkey (Callithrix jacchus). The excretion of major urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and delta 17-2,3-dinor-6-keto-PGF1 alpha (PGI3-M) was estimated as an index of total body synthesis of PGI2 and PGI3, respectively. Following extraction, dinor prostanoid metabolites were separated by capillary gas chromatography and identified by negative ion chemical ionization mass spectrometry. Supplementation of the standard (reference) diet with either sheep fat or sunflower seed oil did not alter the body production of PGI2-M. However, following the tuna fish oil-enriched diet, there occurred not only an increase in urinary PGI2-M (reference 70.7 +/- 9.0; tuna fish oil 115.5 +/- 12.1 ng/g creatinine, P less than 0.05), but also a considerable formation of PGI3-M (62.9 +/- 5.3 ng/g creatinine), which was not seen in any other dietary group; in addition, the urinary level of immmunoreactive 2,3-dinor-thromboxane B2/3 was reduced after ingestion of tuna fish oil. These urinary changes were accompanied by a rise in plasma phospholipid-bound EPA and docosahexaenoic acid (DHA). In addition, tuna fish oil supplementation resulted in a significant reduction in plasma cholesterol (53%) and triacylglycerols (44%). The present study provides for the first time experimental evidence for the in vivo formation of PGI3 in an animal model and also confirms the earlier observations in man following dietary fish oil supplementation.     

4 种不同脂肪源对太平洋鲑生长和体组成的影响

在日粮中添加11.5%的4 种不同来源脂肪饲养180 尾初始重约为110g 的太平洋鲑(Oncorhynchus spp.)于水泥池中56d。实验分4 组,每组3个平行池,每池15尾鱼。研究日粮中4 种不同来源脂肪对淡水养殖太平洋鲑生长性能、体组成与品质的影响。4 组脂肪源分别为鱼油(实验1 组)、大豆油(实验2 组)、大豆磷脂(实验3 组)和玉米油(实验4 组)。实验表明:(1) 实验各组太平洋鲑存活率相似,但大豆磷脂组的特定生长率显著好于鱼油组、大豆油组和玉米油组(P0.05)。大豆磷脂组、大豆油组和玉米油组的饲料效益显著好于鱼油组(P< 0.05); (2) 大豆油组、大豆磷脂组和玉米油组太平洋鲑肠系膜脂肪与肝脏脂肪含量不同程度低于鱼油组,而肌肉中脂肪含量不同程度低于鱼油组; (3) 实验各组太平洋鲑肝脏脂肪、肌肉脂肪和肠脂中总多不饱和脂肪酸组成基本相似,但玉米油组、大豆磷脂组和大豆油组太平洋鲑总n-3 多不饱和脂肪酸比例较鱼油组显著下降,而总n-6 系多不饱和脂肪酸比例显著提高(P<0.05);(4) 玉米油组、大豆磷脂组和大豆油组太平洋鲑血浆中脂肪分解酶、甘油三酯和高密度脂蛋白指标较鱼油组不同程度上升;(5) 实验各组太平洋鲑解剖组织学检查未见异常病理变化。实验结果表明,淡水养殖条件下,太平洋鲑日粮中脂肪以添加大豆磷脂的生长性能最好,大豆油、玉米油和鱼油效果相似,添加玉米油、大豆磷脂和大豆油均不影响太平洋鲑健康状况和品质。       

Dietary Fat Influences the Expression of Contractile and Metabolic Genes in Rat Skeletal Muscle

Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA)-rich), fish oil (n-3 PUFA-rich), or lard (low in PUFAs) were administered to the rats for 4 weeks. Myosin heavy chain (MyHC) isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL) muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.     

Effects of simulated microgravity conditions on carrageenin-induced oedema in rat

The effects of simulated microgravity conditions, using a three-dimensional clinostat (Random Positioning Machine, RPM), on carrageenin-induced paw oedema in rats as a model of local inflammation were evaluated. RPM-exposed animals showed a significant reduction of oedema and a more pronounced decrease in body weight with respect to control groups. Moreover, aspirine (ASA) treatment, an anti-inflammatory agent, on RPM-exposed rats did not exhibit any activity after carrageenin challenge with respect to RPM control animals on the ground. ASA activity on RPM could be prevented by RPM-induced anti-oedematous effect. RPM-induced anti-oedematous effect did not reversed by pre-treatment with the non-selective glucocorticoid receptor antagonist, mifepristone ruling out the supposed influence of an of cortisol release during the RPM treatment.     

Conceivable difference in the anti-inflammatory mechanisms of lipocortins 1 and 5

Human recombinant lipocortins (LCT) 1 and 5 have been expressed in a yeast secretion vector and purified by ion exchange chromatography. The action of the proteins has been investigated in two models of experimental acute inflammation in the rat: carrageenin induced paw oedema and zymosan induced pleurisy. The effects of the proteins on PGE(2) release in vitro by rat macrophages stimulated with zymosan and on rat neutrophil chemotaxis induced by FMLP have also been assessed. LCT-1 significantly inhibited both paw swelling in carrageenin oedema and leukocyte migration in zymosan pleurisy. Moreover it showed a dose dependent, inhibitory effect on PGE(2) release. Neutrophil chemotaxis was only weakly affected by LCT-1. Conversely LCT-5 did not reduce carrageenin oedema and slightly inhibited PGE(2) release, but showed profound, dose dependent inhibitory activity on leukocyte migration in zymosan pleurisy and on neutrophil chemotaxis. These data suggest that LCT-1 acts mainly by interfering with arachidonic acid metabolism via the inhibition of phospholipase A(2). The anti-inflammatory activity of LCT-5, at variance with LCT-1, may be due to a direct effect on cell motility in addition to the interference with arachidonic acid metabolism.     

Effect of dexamethasone on carrageenin-induced inflammation in the lung

To study the anti-inflammatory mechanisms of glucocorticoids, we have compared the effects of intratracheal carrageenin (2.5 mg) on control rats and those in which inflammation was subdued by prior dexamethasone treatment (10 mg/l in drinking water). Inflammation was maximal 48 h post-carrageenin. After dexamethasone, carrageenin caused tittle inflammation or oedema (wet lung (mg), n = 6, mean +/- S.E.M.; control, 995 +/- 51; carrageenin + dexamethasone, 1144 +/- 83; compared with carrageenin alone, 1881 +/- 198), but rats had more lung lavage neutrophils than those given carrageenin alone (PMN x 10(6) /lung, mean +/- S.E.M.; control, 0.055 +/- 0.003; carrageenin + dexamethasone, 8.54 +/- 1.52; compared with carrageenin alone, 6.30 +/- 1.71). Proteolysis and partial inactivation of the anti-inflammatory mediator, lipocortin 1 (Lcl), in carrageenin-instilled rats was offset in those also given dexamethasone, by increased Lc1 levels (intact Lc1 ng/ml lavage fluid, n = 4, mean +/- S.E.M.; control 24 +/- 6; carrageenin 15 +/- 4; carrageenin + dexamethasone, 40 +/- 15). Maintenance of sufficient intact (fully active) extracellular Lc1 may contribute to the actions of glucocorticoids.     

The prostaglandin outflow from perfused mesenteric vasculature of rats fed different fats

The effects of dietary n-6 polyunsaturated fatty acids and replacement with saturated fat or fish oil on the prostaglandin outflow from perfused mesenteric vasculature in rats were studied. Seventy-two weanling male rats were fed ad libitum a semi-synthetic diet supplemented with 10% by weight of oil, composed wholly of n-6 fatty acid-rich evening primrose oil, or replaced partly or completely (25, 50, 75 or 100%) by n-6 fatty acid-deficient fish oil or hydrogenated coconut oil for 8 weeks. The outflows of 6-keto-PGF1 alpha, thromboxane B2, and prostaglandin E from the perfused mesenteric vasculature were measured at 60 min-time point after starting the perfusion. In general, the release of prostanoids from the mesenteric vasculature was significantly reduced in rats fed a diet in which evening primrose oil was partly or completely replaced by either hydrogenated coconut or fish oil. This was probably due to the insufficient conversion of linoleic acid to arachidonic acid. The extent of reduction was greater in fish oil-fed than in hydrogenated coconut oil-fed rats, while the levels of arachidonic acid in aortic phospholipids were similar between these two groups. This result implies that the greater reduction of prostaglandin synthesis in rats fed fish oil was due to the inhibitory effect of eicosapentaenoic and docosahexaenoic acids in fish oil on the conversion of arachidonate to eicosanoids.     

Inverse modifications of heart and liver alpha-tocopherol status by various dietary n-6/n-3 polyunsaturated fatty acid ratios

The effect of dietary n-6/n-3 fatty acid ratio on alpha-tocopherol homeostasis was investigated in rats. Animals were fed diets containing fat (17% w/w) in which the n-6/n-3 ratio varied from 50 to 0.8. This was achieved by combining corn oil, fish oil, and lard. The polyunsaturated to saturated ratio and total alpha-tocopherol remained constant in all diets. Results showed that enrichment of n-3 polyunsaturated fatty acids in the diet, even at a low amount (3.9% w/w), resulted in a dramatic reduction of blood alpha-tocopherol concentration, which, in fact, is the result of a decrease in plasma lipids, since the alpha-tocopherol to total lipids ratio was not significantly altered. The most striking effect observed was a considerable alpha-tocopherol enrichment (x 4) of the heart as its membranes became enriched with n-3 polyunsaturated fatty acids. This process appeared even with a low amount of fish oil (3.9% w/w) added to the diet. Accordingly, a strong positive correlation was found between heart alpha-tocopherol and docosahexaenoic acid (r = 0.86) or docosahexaenoic acid plus eicosapentaenoic acid levels (r = 0.84). Conversely, the liver alpha-tocopherol level dropped dramatically when n-3 polyunsaturated fatty acids were gradually added to the diet. It is concluded that fish oil intake dramatically alters the alpha-tocopherol homeostasis in rats.     

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.     

Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet

The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10 days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3. Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two groups but not different from either group. There were no differences in the milk leptin content between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for maintaining adequate serum leptin levels in the offspring.     

Leguminous lectins as tools for studying the role of sugar residues in leukocyte recruitment

The natural physiological ligands for selectins are oligosaccharides found in glycoprotein or glycolipid molecules in cell membranes. In order to study the role of sugar residues in the in vivo lectin anti-inflammatory effect, we tested three leguminous lectins with different carbohydrate binding affinities in the peritonitis and paw oedema models induced by carrageenin in rats. L. sericeus lectin was more anti-inflammatory than D. virgata lectin, the effects being reversed by their specific binding sugars (N-acetylglucosamine and alpha-methylmannoside, respectively). However, V. macrocarpa, a galactose-specific lectin, was not anti-inflammatory. The proposed anti-inflammatory activity of lectins could be due to a blockage of neutrophil-selectin carbohydrate ligands. Thus, according to the present data, we suggest an important role for N-acetylglucosamine residue as the major ligand for selectins on rat neutrophil membranes.     

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRalphabeta+CD8alpha+CD8beta-intestinal intraepithelial lymphocytes

Intestinal intraepithelial lymphocytes (IELs) and their cytokines play an important role in the regulation of gut immune response and take part in gut immune barrier function. n-3 polyunsaturated fatty acid (PUFA) is an immunoregulator that has been shown to influence the process of gut inflammation. Interleukin (IL)-15 is a T-cell growth factor that has been shown to influence the differentiation of IEL. The aim of this study was to analyze the effects of dietary n-3 PUFA on IEL. IEL phenotype and cytokine (TNF-alpha, IFN-gamma, IL-4, IL-10 and TGF-beta1) profile were measured by FACS and real-time RT-PCR in healthy adult rats fed with fish oil diet for 90 days. Rats fed with corn oil diet served as controls. Intestinal IL-15 expression was measured by immunohistochemistry and real-time RT-PCR. The results demonstrated a decrease of intestinal IL-15 expression in the fish oil group. Associated with this deduction, n-3 PUFA significantly decreased the proportion of TCRalphabeta+CD8alpha+CD8beta- cells and IEL-derived TNF-alpha, IFN-gamma, IL-4 and IL-10. In conclusion, n-3 PUFA could inhibit intestinal mucosal expression of IL-15 and may influence phenotype and function of IEL through this mechanism.     

The influence of dietary essential fatty acids on uterine C20 and C22 fatty acid composition.

The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition.     

Fish oil supplementation for two generations increases insulin sensitivity in rats

We investigated the effect of fish oil supplementation for two consecutive generations on insulin sensitivity in rats. After the nursing period (21 days), female rats from the same prole were divided into two groups: (a) control group and (b) fish oil group. Female rats were supplemented with water (control) or fish oil at 1 g/kg body weight as a single bolus for 3 months. After this period, female rats were mated with male Wistar rats fed on a balanced chow diet (not supplemented). Female rats continued to receive supplementation throughout gestation and lactation periods. The same treatment was performed for the next two generations (G1 and G2). At 75 days of age, male offspring from G1 and G2 generations from both groups were used in the experiments. G1 rats did not present any difference with control rats. However, G2 rats presented reduction in glycemia and lipidemia and improvement in in vivo insulin sensitivity (model assessment of insulin resistance, insulin tolerance test) as well as in vitro insulin sensitivity in soleus muscle (glucose uptake and metabolism). This effect was associated with increased insulin-stimulated p38 MAP kinase phosphorylation and lower n-6/n-3 fatty acid ratio, but not with activation of proteins from insulin signaling (IR, IRS-1 and Akt). Global DNA methylation was decreased in liver but not in soleus muscle. These results suggest that long-term fish oil supplementation improves insulin sensitivity in association with increased insulin-stimulated p38 activation and decreased n-6:n-3 ratio in skeletal muscle and decreased global DNA methylation in liver.     

A maternal high n-6 fat diet with fish oil supplementation during pregnancy and lactation in rats decreases breast cancer risk in the female offspring

The timing of dietary fat intake may modify breast cancer risk. In addition, n-3 fatty acids reduce, and n-6 fatty acids increase, the risk of breast cancer and a maternal high n-6 fat diet results in a greater risk of breast cancer in the female offspring. We hypothesized that the timing of n-3 fatty acid-enriched fish oil supplementation would be important for reducing the risk of breast cancer. Female rats were fed to a high n-6 fat diet containing 20% of the sunflower oil by weight during pregnancy and lactation, and the female offspring were exposed to fish oil by oral gavage either during the perinatal period via maternal intake or during puberty or adulthood. Exposure during the perinatal period to a maternal high n-6 fat diet with fish oil supplementation significantly reduced the incidence of carcinogen-induced mammary tumors in the female offspring compared to a maternal high n-6 fat diet with no fish oil supplementation or fish oil supplementation later in life (P=.0228 by Cox proportional hazards model). We found that a maternal high n-6 fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than a maternal high n-6 fat diet during lactation. This study suggests that fish oil supplementation during the perinatal period decreases the effect of a maternal high n-6 fat diet on subsequent carcinogen-induced mammary tumor risk, whereas fish oil supplementation during puberty or adulthood does not.     

Effects of n-3 polyunsaturated dietary supplementation on the reproductive capacity of male turkeys

To measure the effects of dietary n-3 polyunsaturated fatty acid (PUFA) supplementation on the reproductive capacity of adult male turkeys in industrial flocks, the males of 22 commercial farms were fed either a standard diet or a fish oil diet enriched in n-3 PUFAs. The fatty acid composition of the spermatozoa and reproductive performance were measured throughout the reproductive period. The fish oil diet very effectively increased the percentage of n-3 fatty acids (FA) (22:5n-3 and 22:6n-3) in spermatozoa and correspondingly decreased the percentage of n-6 PUFAs (20:4-6 and 22:4n-6): the n-3/n-6 ratio in spermatozoa fatty acids were 0.04-0.07 with the standard diet and 0.32-0.4 with the fish oil diet. These changes did not affect the spermatozoa content of n-9 PUFAs, particularly of 22:3n-9 which is abundant in turkey spermatozoa (9-12% of the total fatty acids). The supplementation was effective in the middle as at the end of the reproductive period. The reproductive capacity of males was modified by the diet and the positive effect of the n-3 supplemented diet increased with age (increase in hatching rates of nearly 2 points at 48-58 weeks for males fed fish oil diet). These results indicate that an increase in the dietary ratio of n-3/n-6 PUFAs is valuable to sustain the reproductive capacity of male turkeys especially when they are getting older.     

No altered blood pressure and serum markers of oxidative stress after a long time dietary fish oil in the genetically 9 month-old type-2 diabetes Zucker rat

In this study, we investigated the effect of a high n-3 fatty acid diet (eicosapentaenoic and docosahexaenoic acids) in Zucker obese and lean rats on blood pressure in association with physiological parameters, serum biochemistry and oxidative stress analysis.After 150 days of treatment, dietary fish oil supplementation in Zucker obese rats (9 months of age) reduces bodyweight gain and serum triglyceridemia and nitrite levels, increases serum glucose and angiotensin converting enzyme activity, but does not alter blood pressure, cholesterol levels and serum markers of oxidative stress (malondialdehyde, glutathione), compared to the Zucker rats fed control diet.According to these results, we can consider that after 150 days of treatment, fish oil is not enough to regulate parameters involved in the metabolic syndrome, such as cholesterolemia and blood pressure, in a 9 month-old genetically type-2 diabetes rat.