Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status but not bone mass in piglets

Dietary (n-6) and (n-3) fatty acids have been implicated as important regulators of bone metabolism. The main objective of this research was to define the response of whole-body growth, fatty acid status and bone mass to a reduced dietary (n-6):(n-3) fatty acid ratio. A secondary objective was to determine whether there is an amount of fat x fatty acid ratio interaction for these outcomes. Piglets (n = 32) were randomized to 1 of 4 diets: group 1: [30 g fat/L + (n-6):(n-3) ratio 4.5:1]; group 2: [30 g fat/L + (n-6):(n-3) ratio 9.0:1]; group 3: [60 g fat/L + (n-6):(n-3) ratio 4.5:1]; and group 4: [60 g fat/L + (n-6):(n-3) ratio 9.0:1]. After 21 d, outcomes assessed included growth, fatty acid status and bone mass and metabolism. Growth and bone mass did not differ among the four groups nor did arachidonic acid (AA as g/100 g fatty acids) in plasma, adipose and brain. Piglets fed diets 1 and 3 with the lower (n-6):(n-3) ratio had lower liver AA (P < 0.001). Those fed diets 1 and 2 containing 30 g fat/L had lower docosahexaenoic acid (DHA as g/100 g fatty acids) in liver (P < 0.001), plasma (P = 0.019) and adipose tissue (P = 0.045). However, piglets fed diets 1 and 3 had higher (P < 0.001) brain DHA than those fed diets with a higher (n-6):(n-3) ratio. Higher plasma DHA was associated with less bone resorption (r = -0.44, P = 0.01). Therefore, elevation of dietary (n-3) fatty acids supports growth and fatty acid status while not compromising bone mass. The results may be of relevance to the nutritional management of preterm infants whose DHA status is often too low and bone resorption too high.     

Docosahexaenoic acid and eicosapentaenoic acid affect ovarian prostaglandin levels differently in rats

Prostaglandins (PGs) play a key role in the regulation of ovulation. Typically, ingestion of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) has been found to decrease, whereas arachidonic acid (ARA) increases PG biosynthesis in most systems. We hypothesized that DHA and EPA would decrease ovarian PGE₂, enhancing ovulation, with combined EPA and DHA having the greatest effect, whereas ARA would increase PGE₂, suppressing ovulation. Our objective was to determine how 0.3-g/100-g diet DHA and EPA alone or combined, or ARA would affect tissue composition, ovulation, and PG synthesis in rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid alone reduced ovarian n-6 PUFA attributable to reduced ARA incorporation. Arachidonic acid ingestion reduced and EPA enhanced ovarian n-3 PUFA to levels above what was seen with DHA or DHA/EPA combinations. Docosahexaenoic acid alone increased total PGE 1.5-fold over control, whereas neither differed from the remaining treatments. Increased total PGE with DHA was attributable to elevated PGE₃ with PGE₂ unchanged by diet, and PGE₃ only increased with DHA ingestion alone. Total PGF differed from control with the highest DHA intake, alone or combined with EPA, or with ARA ingestion (P < .05). Increased PGF with DHA was attributable to increased PGF_3α. Experimental diets did not alter ovulation from control. Results indicate that DHA and EPA consumption at human achievable doses differently alters ovarian phospholipids and PGs associated with ovulation with potential for significant 3-series PG without significantly perturbing ovulation.     

Addition of vitamin E to long-chain polyunsaturated fatty acid-enriched diets protects neonatal tissue lipids against peroxidation in rats

Summary Background: Tissue 10:4(n-6) and 22:6(n-3) status have been correlated with neonatal development and growth. Artificial formulas for neonates have been supplemented with long chain polyunsaturated fatty acids (LCP) from animal and marine sources which may enhance sensitivity of cellular membranes to oxidative damage. Diet-derived antioxidants like vitamin E play a key role in the protection of tissue lipids against oxidation. Aim of the study: We seek to determine the influence of dietary vitamin E on tissue sensitivity to oxidative stress in rats fed for 4 weeks on diets enriched in (n-3) and (n-6) long-chain polyunsaturated fatty acids. Methods: Weanling rats received 10% fat diets that provided 18:1(n-9), 18:2(n-6) and 18:3(n-3) in a similar ratio to that of rat milk (group A), supplemented with fish oil (groups B and B+E) and supplemented with (n-6) and (n-3) LCP from an animal phospholipid concentrate (groups C and C+E). Vitamin E (500 mg vitamin E/kg fat) was added to diets B+E and C+E. Tissue fatty acid content and the activities of catalase, superoxide dismutase, glutathione transferase und glutathione peroxidase in liver and brain were measured. Glutathione status, vitamin E and the production of thiobarbituric acid reactive substances (TBARs) after incubation of erythrocyte, liver and brain lipids with inducers of enzymatic or non-enzymatic lipid peroxidation was measured. Results: Group B registered significantly lower total superoxide dismutase acitvity than group B+. Catalase activity was significantly higher in group C than in group C+E. Hepatic total and reduced glutathione levels were decreased in vitamin E supplemented groups compared to unsupplemented ones. TBARs production in erythrocyte lipids was significantly higher in groups B and C compared to vitamin E supplemented groups B+E and C+E. Conclusions: This study shows that the addition of vitamin E protected erythrocyte and liver microsome lipids enriched in (n-3) and (n-6) LCP from lipid peroxidation during the postnatal development of rats. The protection was more effectively in group C+E than in group B+E. Received: 14 January 1999, Accepted: 14 June 1999     

Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils

Docosahexaenoic acid [DHA, 22:6(n-3)], a major component of membrane phospholipids in brain and retina, is profoundly susceptible to oxidative stress in vitro. The extent of this peroxidation in organs when DHA is ingested in mammals, however, is not well elucidated. We investigated the effect of dietary DHA-containing oils (DHA 7.0-7.1 mol/100 mol total fatty acids), in the form of triacylglycerols (TG), ethyl esters (EE) and phospholipids (PL), on tissue lipid metabolism and lipid peroxidation in rats. Groups of Sprague-Dawley rats were fed semipurified diets containing 15 g/100 g test oils and were compared with those fed 80% palm oil and 20% soybean oil as the control (unsupplemented group) for 3 wk. The DHA oil diets markedly increased (P: < 0.05) the levels of DHA in the plasma, liver and kidney, 1.5-1.9, 2.5-3.8 and 2.2-2.5 times the control values, respectively, whereas there was a concomitant reduction (P: < 0.05) in arachidonic acid. All forms of DHA oil caused lower TG concentrations in plasma (P: < 0.05) and liver (P: < 0.05), but had no effect in kidney. The DHA oil-fed rats had greater phospholipid hydroperoxide accumulations in plasma (191-192% of control rats), liver (170-230%) and kidney (250-340%), whereas the alpha-tocopherol level was reduced concomitantly (21-73% of control rats). Consistent with these results, rats fed DHA-containing oils had more thiobarbituric reactive substances in these organs than the controls. Thus, high incorporation of (n-3) fatty acids (mainly DHA) into plasma and tissue lipids due to DHA-containing oil ingestion may undesirably affect tissues by enhancing susceptibility of membranes to lipid peroxidation and by disrupting the antioxidant system.     

Efficacy and safety of docosahexaenoic acid and arachidonic acid addition to infant formulas: can one buy better vision and intelligence?

Long chain polyunsaturated fatty acids (LCPUFA) namely arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are highly concentrated in the phospholipid bilayer of biologically active brain and retinal neural membranes and are important in phototransduction and neuronal function. The rationale for adding these LCPUFA to infant formula (IF) was primarily because of their presence in large quantities in the retina and brain and in human milk. In addition, infants fed IF containing LCPUFA and breastfed infants have comparable ARA and DHA levels in red cell and plasma, in contrast to the lower ARA and DHA levels in those fed IF containing only the essential fatty acids: linoleic (LA, 18:2n-6) and linolenic (LNA, 18:3n-3), the precursors to ARA and DHA, respectively. However, functional benefits in particular visual or neural development from IF containing LCPUFA remains controversial. Potential for excessive and/or imbalanced intake of n-6 and n-3 fatty acids exists with increasing fortification of LCPUFA to infant foods other than IF.     

Docosahexaenoic acid biostatus is associated with event-related functional connectivity in cortical attention networks of typically developing children

Objective: Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children.

Methods: Male children (aged 8–10 years, n?=?36) were divided into ‘low-DHA’ (n?=?18) and ‘high-DHA’ (n?=?18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region.

Results: Erythrocyte DHA composition in the low-DHA group (2.6?±?0.9%) was significantly lower than the high-DHA group (4.1?±?1.1%, P?≤?0.0001). Fish intake frequency was greater in the high-DHA group (P?=?0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P?P?=?0.03) which was inversely correlated with erythrocyte DHA among all subjects.

Discussion: These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.     

Dietary docosahexaenoic acid-enriched phospholipids normalize urinary melatonin excretion in adult (n-3) polyunsaturated fatty acid-deficient rats.

Melatonin (MEL) plays an essential role in physiologic functions associated with darkness. We examined the effects of docosahexaenoic acid (DHA)-enriched phospholipids from pig brains (BPL) or hen eggs (EPL), as sources of DHA, on lipid FA composition of pineal membranes and daytime and nighttime concentrations of 6-sulfatoxymelatonin (aMT6) in adult male control and (n-3)-deficient rats fed BPL and EPL diets for 5 wk. In two experiments, at 3 wk of age, rats were divided into subgroups and fed semipurified diets containing either peanut oil [(n-3)-deficient group] or peanut plus rapeseed oil (control group) and two dietary formulas containing either 3.5 g/100 g diet of BPL (Experiment 1) or 5.0 g/100 g diet of EPL (Experiment 2). BPL and EPL diets provided approximately 200 mg of DHA/100 g diet. During the daytime, aMT6 concentrations were not significantly different among groups. Conversely, the (n-3)-deficient rats had significantly lower nighttime aMT6 concentrations than the control rats. BPL and EPL did not affect urinary nighttime aMT6 concentration in the control group, whereas (n-3)-deficient + BPL or EPL groups exhibited significantly higher nighttime aMT6 concentrations than the (n-3)-deficient group (76 and 110%, respectively). The level of DHA was significantly higher in the pineal glands of control rats than in (n-3)-deficient rats. In rats fed EPL and BPL, the level of DHA reached a plateau, between 10 and 11 mg/100 mg total fatty acids in control + BPL or EPL and (n-3)-deficient + BPL or EPL groups. These findings suggest that new DHA-enriched formulas may be used as an efficient alternative source of (n-3) polyunsaturated fatty acids to normalize MEL secretion.     

Diet (n-3) polyunsaturated fatty acid content and parity interact to alter maternal rat brain phospholipid fatty acid composition

Low tissue levels of (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. The effects of 1-4 sequential reproductive cycles on maternal brain phospholipid fatty acid composition were determined in female rats fed diets containing alpha-linolenic acid (ALA), containing ALA and pre-formed DHA (ALA+DHA), or lacking ALA (low-ALA). Virgin females, fed the diets for commensurate durations served as a control for reproduction. Whole-brain total phospholipid composition was determined at weaning by TLC/GC. A single reproductive cycle on the low-ALA diet decreased brain DHA content by 18% compared to ALA primiparas (P < 0.05), accompanied by incorporation of docosapentaenoic acid ((n-6) DPA, 22:5(n-6)) to 280% of ALA primiparas (P < 0.05). DHA was not further decreased after subsequent cycles; however, there was an additional increase in (n-6) DPA after the second cycle (P < 0.05). Brain DHA of virgin females fed the low-ALA diet for 27 wk decreased 15% (P < 0.05), but was accompanied by a more modest increase in (n-6) DPA than in parous low-ALA dams (P < 0.05). Virgin females and parous dams fed the diet containing ALA+DHA exhibited only minor changes in brain fatty acid composition. These observations demonstrate that brain DHA content of adult animals is vulnerable to depletion under dietary conditions that supply inadequate (n-3) PUFAs, that this effect is augmented by the physiological demands of pregnancy and lactation, and that maternal diet and parity interact to affect maternal brain PUFA status.     

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

Background

Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates.

Methods

Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics.

Results

In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA.

Conclusion

The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.     

Dietary n-3 polyunsaturated fatty acids increase oxidative stress in rats with intracerebral hemorrhagic stroke

Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition–93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA–fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid–reactive substance content was significantly (P < .05) higher in 1% EPA + DHA–fed rats than in 0% and 0.5% EPA + DHA–fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.     

The neuroprotective effect of fish n-3 fatty acids in the hippocampus of diabetic rats

Abstract

Introduction: Diabetes mellitus may lead to functional and structural changes in the brain. Fish oil is a rich source of n-3 essential fatty acids (EFA) such as eicosapentaenoic and docosahexoenoic acids. We examined the neuroprotective effects of fish n-3 EFA in the hippocampus of diabetic rats.

Materials and methods: Nineteen adult male rats were divided into three groups. Group I (control; n = 6) was fed a normal rat diet. Group II (diabetic; n = 6) was fed a normal rat diet and streptozotocin (STZ) was administered to induce diabetes mellitus. Group III (n-3 + diabetic; n = 7) was fed a normal rat diet and fish n-3 EFA (Marincap^®, 0.4 g/kg/day) for 8 weeks and STZ was administered to induce diabetes mellitus. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus after the animals were sacrificed. The right hemisphere was completely blocked. The sections were stained with Cresyl Violet and apoptotic neurons were counted in the hippocampus.

Results: The levels of MDA and activities of SOD and CAT increased in diabetic rats compared to control rats. However, the levels of MDA and activities of SOD and CAT decreased in n-3 + diabetic rats compared to diabetic rats. Also, the number of apoptotic neurons increased in diabetic rats compared to control rats and decreased in n-3 + diabetic rats compared to diabetic rats.

Conclusions: Fish n-3 EFA reduces oxidative stress and induces apoptotic changes in the hippocampus of STZ-diabetic rats. The addition of fish n-3 EFA to diets may be useful to prevent functional and structural changes to cerebral centers due to diabetes mellitus.     

Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.     

Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids,desaturase activity indices,and urinary prostaglandin E in women

Compared with diets high in fat, low-fat diets are associated with reduced risk of cardiovascular disease. We hypothesized that a low-fat (LF) (20% fat) and an LF high–omega-3 (n-3) fatty acid diet (LFn3) (23% fat with 3% as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid [DHA]) would enhance n-3 composition of plasma phospholipid fatty acid and reduce urinary prostaglandin E₂ (PGE₂) relative to a high-fat diet (HF) (40% fat) and that these changes would be associated with alterations in δ5 desaturase (D5D) and δ6 desaturase (D6D) activity. Phospholipid fatty acids and urinary PGE₂ were measured, and D5D and D6D activity indices calculated in a crossover trial in 17 postmenopausal women fed each of 3 test diets (HF, LF, and LFn3) for 8-week feeding periods. Desaturase activity indices were calculated as D5D, 20:4n-6/20:3n-6, and D6D, 20:3n-6/18:2n-6. Plasma phospholipid fatty acid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid (DPA), DHA, and total n-3 fatty acids increased, whereas linoleic acid and arachidonic acid decreased with consumption of LFn3. The LF resulted in enhanced arachidonic acid and DHA. High fat reduced D6D, whereas both HF and LF increased D5D. Urinary PGE₂ was reduced in response to both the LF and LFn3 diets. Low-fat diets, with or without long-chain n-3 fatty acids, promote positive health effects due in part to favorable alteration of plasma phospholipid fatty acid profiles and modification in desaturase activity indices, suggesting that the type and amount of fat consumed are modifiable risk factors for the prevention of cardiovascular disease.     

不同膳食脂肪酸构成影响MNU诱导大鼠乳腺肿瘤发生的研究

目的:探讨不同膳食脂肪酸对甲基亚硝基脲(MNU)诱导的大鼠乳腺肿瘤发生的影响。方法:用含15%脂肪(wt/wt)的半合成饲料喂养雌性SD大鼠。大鼠50d龄时,分8组喂养8种不同膳食脂肪酸组成的饲料,即SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3和S/M/P为1∶2∶(1其中n-6/n-3为1∶1),每组又分肿瘤组和对喂组,肿瘤组,单次腹腔注射MNU(50mg/kgbw),相应的对喂组注射生理盐水,持续喂养18w。观察各组大鼠体重增长、乳腺肿瘤发生率、肿瘤多发率及肿瘤潜伏期等。结果:除喂养n-3PUFA的大鼠在实验6w后出现体重增长受阻外,其它组别的大鼠体重增长无明显差异。各对喂组大鼠均无乳腺肿瘤发生,而在MNU注射组中,喂养n-3PUFA的大鼠也无乳腺肿瘤发生,但喂养SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和S/M/P(1/2/1)大鼠乳腺肿瘤诱发率是1∶1n-6/n-3的2倍,且喂养1∶1n-6/n-3的大鼠,其肿瘤发生的潜伏期也最长。结论:不同膳食脂肪酸构成对MNU诱导的大鼠乳腺肿瘤发生影响不同。,1∶1n-6/n-3膳食脂肪酸构成能有效抑制MNU诱导的乳腺肿瘤发生。     

Dietary (n-3) fatty acids affect rat heart, liver and aorta protective enzyme activities and lipid peroxidation

In a 16-wk study, weanling Wistar rats (32 males and 32 females) were fed a modified AIN-76 diet containing 20% fat with various (n-3) fatty acids. All dietary fats provided the same amount of saturates, monounsaturates, and total essential fatty acids [(n-6) + (n-3)]. The control diet contained lard/corn oil (L/CO). The other diets contained (n-3) fatty acids from linseed oil (LSO), from linseed oil + menhaden oil (LSO + MO) or from menhaden oil (MO). The (n-3) diets reduced total and HDL-cholesterol, particularly in rats fed the MO diet. Platelet thromboxane levels were equally depressed by the LSO and MO diets. Dietary (n-3) fatty acids significantly elevated docosahexaenoic acid in livers and hearts of male and female rats, with females reaching higher levels. This increase was accompanied by reduced arachidonic acid, except for hearts of females in which the major decrease was in linoleic acid. Overall, enzyme activities in the MO-fed group were decreased to the following levels (relative to the activity in the control group): heart Mn superoxide dismutase (SOD), 28%; liver CuZnSOD, 82%; aorta CuZnSOD, 32%. Greater reductions in these enzyme activities were seen in the female rats fed the MO diet compared with male rats. Lipid peroxidation, assessed by urinary, heart and liver thiobarbituric acid reactants, was increased by dietary (n-3) fatty acids (MO greater than LSO + MO greater than LSO greater than L/CO) and was higher in females than in males. These results indicate that enhanced lipid peroxidation occurs with the increased oxidative stress of elevated tissue (n-3) fatty acids accompanied by reduced SOD activity.     

Long-chain (n-3) polyunsaturated fatty acids are more efficient than alpha-linolenic acid in improving electroretinogram responses of puppies exposed during gestation, lactation, and weaning

Long-chain PUFAs (LCPUFAs) are essential for proper neural and retinal development in many mammalian species. We investigated puppies born to dogs fed diets containing varying amounts of vegetable and marine (n-3) fatty acids during gestation/lactation. The fatty acid compositions of dogs' milk and puppy plasma phospholipids were evaluated, and electroretinographic responses of the young dogs were determined after they were weaned to the same diets. Dogs' milk fatty acid composition reflected the diets fed during gestation/lactation. The milk of dogs fed a high alpha-linolenic acid (ALA) diet was enriched in ALA but not docosahexaenoic acid (DHA). Puppies fed this ALA-enriched milk accumulated more plasma phospholipid DHA than the low (n-3) fatty acid group. However, this accumulation was less than that obtained in puppies fed preformed DHA during development and suckling (P < 0.05). Electroretinograms (ERGs) of 12-wk-old puppies revealed significantly improved visual performance in dogs fed the highest amounts of (n-3) LCPUFAs (P < 0.05). These puppies demonstrated improved rod response (improved amplitude and implicit time of the a-wave, P < 0.05). Puppies from the low (n-3) fatty acid group exhibited the poorest ERG responses compared with the high-marine or high-vegetable (n-3) groups. A novel parameter devised in this study, the initial intensity at which the a-wave was detectable (i.e., threshold intensity), also demonstrated that retinal response of puppies consuming the (n-3) LCPUFA-containing diets occurred at lower light intensity, thereby exhibiting greater rod sensitivity, than the other diet groups. These findings indicate that preformed dietary (n-3) LCPUFA is more effective than ALA in enriching plasma DHA during perinatal development and results in improved visual performance in developing dogs.     

Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men

High linoleic acid (LA) intakes have been suggested to reduce alpha-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 +/- 0.12% and 1.0 +/- 0.05%, and 10.5 +/- 0.53% and 1.1 +/- 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean +/- SEM) 20.7 +/- 1.52 and 12.9 +/- 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.     

不同膳食脂肪酸对大鼠乳腺癌组织脂肪酸组成和脂代谢基因表达的影响

目的探讨不同膳食脂肪酸组成影响大鼠乳腺癌发生、发展的可能分子机制。方法用8种不同膳食脂肪酸组成(SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3、1∶2∶1S/M/P其中n-6/n-31∶1)喂养SD雌性大鼠,并在大鼠乳腺癌模型的基础上,用气相色谱内标法观察大鼠乳腺组织脂肪酸组成改变,RT-PCR分析组织脂代谢调控基因(FAS、COX-2和5-LOX)的表达。结果在不同膳食脂肪酸构成中,只有1∶1n-6/n-3能有效抑制大鼠乳腺癌的发生。不同膳食脂肪酸构成可导致大鼠乳腺组织脂肪酸组成发生相应变化,且各组间的脂肪酸含量有显著差异。高乳腺癌诱发的SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和1∶2∶1S/M/P喂养组乳腺组织含有较多的C18∶1、C18∶2和C20∶4,而EPA和DHA含量极少。无或低乳腺癌诱发的n-3PUFA和1∶1n-6/n-3喂养组乳腺组织EPA和DHA明显增多,C20∶4含量显著减少。RT-PCR结果显示1∶1n-6/n-3低诱癌组较相应对喂组上调FAS、COX-2和5-LOXmRNA表达力度明显弱于其它高乳腺癌诱发组。结论不同膳食脂肪酸组成能明显改变大鼠乳腺组织脂肪酸组成,进而影响脂代谢基因FAS、COX-2和5-LOX表达,可能是大鼠乳腺癌发生的分子机制之一。     

Dietary polyunsaturated fat that is low in (n-3) and high in (n-6) fatty acids alters the SNARE protein complex and nitrosylation in rat hippocampus

Docosahexaenoic acid [DHA, 22:6(n-3)] is enriched in brain membrane phospholipids and is important to brain development and function through its influence on neurite outgrowth and neurotransmitter secretion. Fusion of intracellular vesicles with the plasma membrane involving SNARE [soluble N-ethylmaleimide-sensitive fusion (NSF) protein attachment protein receptor] protein assembly, membrane fusion, and then disassembly are events common in membrane extension and neurotransmitter release. We determined whether feeding an (n-3) fatty acid-deficient diet, known to reduce brain phospholipid DHA, alters SNARE protein and SNARE complex expression or protein nitrosylation in the hippocampus of rats. Female rats were fed diets with 1.3 or 0.02% energy (n-3) alpha-linolenic acid from 2 wk before gestation then throughout gestation and lactation (n = 8/diet), and the male offspring were weaned to the maternal diet. Hippocampus phospholipid fatty acids and SNARE proteins were determined in male offspring at 90 d of age. Hippocampus phospholipid DHA was lower and (n-6) docosapentaenoic acid [DPA, 22:5(n-6)] was higher in the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). Multiplex Western blots using antibodies to syntaxin, synaptosome-associated protein of 25kDa (SNAP-25), and complexin II, showed higher ternary SNARE complexes but no differences in syntaxin, SNAP-25, or complex II expression in hippocampus of the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). S-nitrosylation of syntaxin was also significantly lower in the (n-3) fatty acid-deficient rats than in the control group. These studies suggest that altered SNARE complex binding or disassembly could be important in explaining the diverse cellular events associated with altered tissue DHA.     

Menhaden oil inhibited gamma-glutamyltransferase-positive altered hepatic foci in female Sprague-Dawley rats

Feeding menhaden oil, high in n-3 fatty acids, or a mixture of lard and corn oil with a polyunsaturated-to-monounsaturated fatty acid ratio of 1:1 was hypothesized to inhibit promotion of hepatocarcinogenesis in rats by decreasing hepatic prostaglandin (PG) levels. Ten-day-old female Sprague-Dawley rats were injected with diethylnitrosamine (DEN, 15 mg/kg body wt ip). At 4 wk of age, rats were fed fumonisin B1(50 mg/kg diet) for 5 wk in diets containing 14% lard + 6% corn oil, 10% lard + 10% corn oil, 14% menhaden oil + 6% corn oil, and 7% menhaden oil + 13% corn oil. Plasma alanine aminotransferase activity was 20% lower in rats fed 10% lard than in rats fed the other diets (P < 0.05). In menhaden oil-fed rats, total plasma cholesterol concentrations decreased 26% (P < 0.05) and hepatic phospholipid C20:5n-3, C22:5n-3, and C22:6n-3 fatty acid concentrations increased compared with lard-fed rats. Hepatic n-3 fatty acids were threefold greater in rats fed 10% lard than in rats fed 14% lard. The liver-associated natural killer cell activity in rats fed menhaden oil was 58% lower than in rats fed lard (P < 0.03). Rats fed lard had threefold (P < 0.05) greater area of _-glutamyltransferase-positive altered hepatic foci (AHF) than did rats fed menhaden oil. There was no significant difference in placental glutathione S-transferase-positive AHF among the groups. Hepatic PGF2alpha production was 60-80% greater in rats fed 14% lard than in rats fed the other diets (P < 0.05). Hepatic PGE2 was 48% less in rats fed 14%; menhaden oil than in rats fed 14% lard (P < 0.05). Although gamma-glutamyltransferase-positive focal area was inhibited by menhaden oil, only 14% menhaden oil inhibited PGE2. Feeding 10% lard inhibited PGF2alpha, but not the development of AHF. Therefore, decreased hepatic PGs did not explain the inhibition of carcinogenesis.