Dietary Linoleic Acid Research Articles

Effect of dietary DHA on DHA levels in retinal rod outer segments in young versus mature rats.

We compared the effect of direct supplementation with docosahexaenoic acid (DHA) on the fatty acid composition of the liver and the rod outer segment (ROS) membranes of the retina in young (five-week-old) and mature (one-year-old) rats. In young rats, a high content of DHA in the diet (9.7% of total energy) effectively increased the proportion of DHA in ROS membranes (41.8%), compared with the proportion observed in a linoleic acid (LA) diet group (control, 31.6%). The proportion of DHA was also significantly higher in the livers of young DHA-fed rats. These results show that direct supplementation with DHA is very effective in increasing DHA levels in the ROS membranes and livers of developing animals. In contrast, in mature rats there was no significant increase in the proportion of DHA in the ROS membranes, even after the highest dose (8.4% of total energy) of DHA, although the proportion of DHA was significantly higher in the livers of DHA-fed rats. The changes in fatty acid composition in the ROS membranes were different in young and mature rats fed high-DHA diets. Our findings indicate that mature rats maintain a constant level of DHA in the ROS membranes even after being directly supplemented with high doses of DHA.

Linoleic acid, but not oleic acid, upregulates the production of interleukin-8 by human intestinal smooth muscle cells isolated from patients with Crohn's disease

Background & aims: Crohn's disease is a chronic inflammatory bowel disease (IBD) of unknown etiology. In this study, we investigated the hypothesis that dietary fatty acids, linoleic acid (LA) and oleic acid (OA), could be involved in the inflammatory response through stimulation of the neutrophil chemokine, IL-8. Methods: Human intestinal smooth muscle (HISM) cells were isolated from normal patients and patients with Crohn's disease and cultured for 24 h with LA or OA in the presence or absence of oxidative stress. The concentrations of IL-8 were measured in the media and cellular oxidative stress was quantitated by measurement of thiobarbituric acid reactive substances (TBARSs). Results: Spontaneous production of IL-8 was significantly higher in HISM cells isolated from Crohn's bowel compared to control bowel. LA caused a marked, nine-fold, increase in IL-8 secretion by Crohn's cells, an effect that could be simulated in normal HISM cells by co-incubation of LA with an oxidizing solution (Ox) composed of hypoxanthine+xanthine oxidase+FeSO 4 (OxLA). These effects were inhibited by vitamins C and E. Treatment of Crohn's cells with OxLA did not further increase IL-8 over that of LA alone. The effect of LA alone was not associated with an increase in cellular oxidative stress as quantitated by TBARSs. In contrast to the results with LA, treatment with OA or OxOA did not increase IL-8 in either normal or Crohn's cells. In addition, OA protected Crohn's cells from the increase in TBARSs induced by Ox. In contrast to IL-8, spontaneous production of monocyte chemotactic protein (MCP-1) was significantly lower in Crohn's HISM cells as compared to normal cells and exposure to OxLA did not increase its production. Conclusions: LA, but not OA, increased the production of IL-8 by HISM cells. These results suggest that replacement of LA by OA in the diet of Crohn's patients and increased intake of a diet rich in antioxidants could be beneficial in decreasing inflammatory activity in Crohn's disease.

Dietary docosahexaenoic acid protects against N-methyl- N-nitrosourea-induced retinal degeneration in rats

The effect of dietary intake of specific types of fatty acids on retinal degeneration due to N-methyl- N-nitrosourea (MNU)-induced photoreceptor cell apoptosis was evaluated. Fifty-day-old female Sprague–Dawley rats were given a single intraperitoneal injection of 50 mg kg −1 body weight of MNU, and were then switched to one of five different diets containing the following fatty acids at the following weight percentages: 10% linoleic acid (LA); 9·5% palmitic acid (PA) and 0·5% LA; 9·5% eicosapentaenoic acid (EPA) and 0·5% LA; 4·75% EPA, 4·75% docosahexaenoic acid (DHA) and 0·5% LA; or 9·5% DHA and 0·5% LA. When rats developed MNU-induced mammary tumors with a diameter of ≧1 cm, or at the termination of the experiment (20 weeks after MNU injection), retinal tissue samples were obtained and examined. Incidence and severity of retinal damage were compared by histologic examination. MNU-induced retinal degeneration was prevented in rats fed the diet containing 9·5% DHA (4·75% DHA was less effective), whereas it was accelerated in rats fed the 10% LA diet. Over the course of the 20-week experimental period, the fatty acid composition of serum reflected differences in dietary fatty acids. The present results indicate that a diet containing 9·5% DHA can counteract MNU retinotoxicity in the rat retina. DHA may play a role in protection against MNU-induced photoreceptor cell apoptosis in the rat retina.

Dietary linolenic acid and carotid atherosclerosis: the National Heart, Lung, and Blood Institute Family Heart Study

Dietary intake of linolenic acid is associated with a lower risk of cardiovascular disease mortality. However, it is unknown whether linolenic acid is associated with a lower risk of carotid atherosclerosis. The objective was to examine the association between dietary linolenic acid and the presence of atherosclerotic plaques and the intima-media thickness of the carotid arteries. In a cross-sectional design, we studied 1575 white participants of the National Heart, Lung, and Blood Institute Family Heart Study who were free of coronary artery disease, stroke, hypertension, and diabetes mellitus. High-resolution ultrasound was used to assess intima-media thickness and the presence of carotid plaques beginning 1 cm below to 1 cm above the carotid bulb. We used logistic regression and a generalized linear model for the analyses. From the lowest to the highest quartile of linolenic acid intake, the prevalence odds ratio (95% CI) of a carotid plaque was 1.0 (reference), 0.47 (0.30, 0.73), 0.38 (0.22, 0.66), and 0.49 (0.26, 0.94), respectively, in a model that adjusted for age, sex, energy intake, waist-to-hip ratio, education, field center, smoking, and the consumption of linoleic acid, saturated fat, fish, and vegetables. Linoleic acid, fish long-chain fatty acids, and fish consumption were not significantly related to carotid artery disease. Linolenic acid was inversely related to thickness of the internal and bifurcation segments of the carotid arteries but not to the common carotid artery. Higher consumption of total linolenic acid is associated with a lower prevalence odds of carotid plaques and with lesser thickness of segment-specific carotid intima-media thickness.

Effect of soybean leci-vita product on serum lipids and fatty acid composition in patients with elevated serum cholesterol and triglyceride levels

The study was designed to examine the effects of soybean Leci-Vita, product rich in polyunsaturated phospholipids (with 7% lecithin, 17% soy protein) on serum lipids and serum and erythrocyte phospholipid fatty acid composition in patients with different types of hyperlipidemia. 106 patients with isolated hypertriglyceridemia (IHTG), combined hyperlipidemia (CHL) and isolated hypercholesterolemia (IHCH), aged 40-70 years, were given 20g of Leci-Vita powder as a water suspension in a single evening dose during the follow up period of 24 weeks. Patients kept their individual diet relatively constant. Treatment was associated with significant decrease in total cholesterol and triglyceride levels by 18% and 35% respectively. LDL-cholesterol decreased 32% and HDL-cholesterol increased 10%. Our study shows a 38% decrease in LDL-cholesterol in CHL, 32% in IHCH and 8% in IHTG and 18% HDL-cholesterol increase in CHL patients. Triglyceride levels decreased in patients with IHTG and CHL 34% and 26% respectively. Our results show increase in PUFA/SFA ratio in serum phospholipids and increased PUFA n-6 in erythrocyte phospholipids that clearly reflects the dietary linoleic acid content in Leci-Vita. Added to a regular diet, soybean Leci-Vita product significantly reduced total and LDL-cholesterol and triglyceride levels. HDL cholesterol was significantly increased and phospholipid fatty acid content was more favourable as a result of 24-week treatment.

Activity and mRNA levels of enzymes involved in hepatic fatty acid synthesis and oxidation in mice fed conjugated linoleic acid

The effects of dietary conjugated linoleic acid (CLA) on the activity and mRNA levels of hepatic enzymes involved in fatty acid synthesis and oxidation were examined in mice. In the first experiment, male ICR and C57BL/6J mice were fed diets containing either a 1.5% fatty acid preparation rich in CLA or a preparation rich in linoleic acid. In the second experiment, male ICR mice were fed diets containing either 1.5% linoleic acid, palmitic acid or the CLA preparation. After 21 days, CLA relative to linoleic acid greatly decreased white adipose tissue mass but caused hepatomegaly accompanying an approximate 10-fold increase in the tissue triacylglycerol content irrespective of mouse strain. CLA compared to linoleic acid greatly increased the activity and mRNA levels of various lipogenic enzymes in both experiments. Moreover, CLA increased the mRNA expression of Δ 6- and Δ 5-desaturases, and sterol regulatory element binding protein-1 (SREBP-1). The mitochondrial and peroxisomal palmitoyl-CoA oxidation rate was about 2.5-fold higher in mice fed CLA than in those fed linoleic acid in both experiments. The increase was associated with the up-regulation of the activity and mRNA expression of various fatty acid oxidation enzymes. The palmitic acid diet compared to the linoleic acid diet was rather ineffective in modulating the hepatic lipid levels or activity and mRNA levels of enzymes in fatty acid metabolism. It is apparent that dietary CLA concomitantly increases the activity and mRNA levels of enzymes involved in fatty acid synthesis and oxidation, and desaturation of polyunsaturated fatty acid in the mouse liver. Both the activation of peroxisomal proliferator α and up-regulation of SREBP-1 may be responsible for this.

Impact of dietary soybean oil versus medium-chain triglycerides on plasma fatty acids in goats

The influence on lipid metabolism of dietary soybean oil with 52.6% linoleic acid (C18:2 n-6), was studied in 2-year-old, male-castrated Dutch white goats. A medium-chain triglycerides-product (MCT) containing 48.9% caprylic (C8:0) and 41.0% capric acid (C10:0) was used as control oil. Six goats were fed the diets containing either soybean oil or MCT according to a 21×21 days cross-over design. The rations contained about 15% crude fat in the dietary dry matter. The soybean oil diet significantly ( P<0.05) increased the absolute amount of linoleic acid in plasma lipids. The plasma contents of heptadecanoic acid (C17:0) and heptadecenoic acid (C17:1) were decreased by feeding the soybean oil diet ( P<0.05). The fatty acid composition of red blood cells was not differently affected by the dietary fats. Dietary soybean oil versus MCT significantly ( P<0.05) increased plasma total cholesterol by 47%, HDL cholesterol by 50% and phospholipids by 39%, but left plasma triglycerides and non-esterified fatty acids unchanged ( P>0.05). This study provides evidence that dietary linoleic acid can escape from biohydrogenation in the rumen of goats and shows that the type of dietary fat has a marked impact on lipid metabolism in goats.

Influence of Dietary Linoleic Acid Intake with Different Fat Intakes on Arachidonic Acid Concentrations in Plasma and Platelet Lipids and Eicosanoid Biosynthesis in Female Volunteers

Background/Aim: N-6 fatty acids are considered to promote diseases prevalent in industrialized countries and characterized by an increased eicosanoid biosynthesis from arachidonic acid (AA). We investigated the impact of the linoleic acid (LA) intake on AA levels in humans. Methods: Six healthy female volunteers (age range 23–34 years) were given liquid formula diets (LFD) devoid of AA for 6 weeks, providing a constant intake of zero energy% (LFD 0: protein 15%, carbohydrates 85%) or 20 energy% (LFD 20: protein 15%, carbohydrates 55%, fat 30%) LA, for 3 weeks each. Fatty acids of plasma cholesteryl esters and platelet lipids were determined each week, and the prostaglandin biosynthesis was measured in 24-hour urine samples. Results: LFD 0 increased (+31% of initial value) and LFD 20 lowered (–30% of initial value) the percentage of AA in plasma cholesteryl esters and platelet lipids. Moreover, absence of dietary AA lowered the percentages of AA in plasma (–31% week 0 vs. week 6) and platelet (–11%) lipids, indicating a low transformation of LA. LFD 0 reduced urinary metabolite levels of prostaglandins D, E, and F in 24-hour urine samples (–48%, p < 0.001) within 24 h, but did not significantly affect platelet aggregation (–10%) and thromboxane formation (–25%). LFD 20 significantly lowered platelet aggregation (–25%) and thromboxane formation (–43%). The prostaglandin metabolite levels increased during the first 10 days, declined thereafter, and were lower than the preexperimental values at the end of the 3-week period. Conclusions: The results show that dietary LA does not increase the AA levels in plasma or platelet lipids and does not persistently contribute to prostaglandin biosynthesis which is increased by AA intake with Western diets.

Expression of the dietary isotope signal in the compound‐specific δ13C values of pig bone lipids and amino acids

AbstractPigs were raised on six isotopically controlled diets to examine the dietary macronutrients used in the synthesis of bulk bone biochemical components (apatite, collagen and lipids) and individual compounds (bone fatty acids, cholesterol and amino acids from collagen). δ13C values of apatite and bulk bone lipids reflected those of the whole diet, with Δ13Capatite‐wholediet = 10.2 ± 1.3‰ and Δ13Cbonelipids‐wholediet = −2.4 ± 0.7‰. A wide variation observed in the Δ13Ccollagen‐wholediet values (0.5 to 6.1‰) was hypothesized to reflect the relative importance of (i) the direct incorporation of essential amino acids, and (ii) the balance between direct incorporation and de novo synthesis of non‐essential amino acids. Linear regression (n = 6) was used to assess the relationship between the δ13C values of whole diet and bulk bone components and individual compounds. Whole diet δ13C values showed a strong correlation with those of bone cholesterol (R2 = 0.81) and non‐essential fatty acids (0.97 ≤ R2 ≤ 0.99). Not surprisingly, bone linoleic acid δ13C values correlated well with dietary linoleic acid (R2 = 0.95). Mass balance calculations using the δ13C values of single amino acids accurately predicted the δ13C value of whole collagen. The δ13C values of whole diet were well correlated with those of the non‐essential amino acids, alanine (R2 = 0.85) and glutamate (R2 = 0.96) in collagen. The essential amino acids leucine (Δ13Ccollagenleu‐dietleu = 0.5 ± 1.2‰) and phenylalanine (Δ13Ccollagenphe‐dietphe = −0.6 ± 0.6‰) showed little isotopic fractionation between diet and bone collagen. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Effect of Docosahexaenoic Acid and Ascorbate on Peroxidation of Retinal Membranes of ODS Rats

Mutant male osteogenic disorder Shionogi (ODS) rats, unable to synthesize ascorbic acid, were fed diets containing a high content of docosahexaenoic acid (DHA) and different amounts of ascorbic acid, to study the effect of DHA on peroxidative susceptibility of the retina and possible antioxidant action of ascorbic acid. ODS rats were fed from 7 weeks of age with diets containing high DHA (6.4% of total energy). A control group received a diet high in linoleic acid. The diets also contained varying amounts of ascorbic acid. Fatty acid compositions and phospholipid hydroperoxides in rod outer segment (ROS) membranes, and retinal ascorbic acid were analyzed. DHA in ROS membranes was significantly increased in rats fed high DHA, compared with the linoleic acid diet. Levels of phospholipid hydroperoxides in the DHA-fed rats were significantly higher than the linoleic acid-fed rats. Ascorbic acid supplementation did not suppress the phospholipid hydroperoxide levels after a high DHA diet, even when the supplement increased the content of retinal ascorbic acid. In conclusion, high DHA feeding induced a marked increase of phospholipid hydroperoxides in ROS membranes of ODS rats. Supplementation of ascorbic acid did not reverse this increase.

Conjugated Linoleic Acid Reduces Hepatic Microsomal Triacylglycerol Transfer Protein Activity and Hepatic Triacylglycerol Mass in Obese Rats.

Conjugated linoleic acid (CLA) is known to modulate lipid and lipoprotein metabolism. We examined the effects of dietary CLA (1 and 2%) on hepatic microsomal triacylglycerol transfer protein (MTP) activity, known to be essential for the assembly/secretion of the apolipoprotein B-containing lipoproteins, and lipid concentrations of liver and plasma in OLETF obese rats. A significant reduction in hepatic MTP activity in CLA-fed rats in comparison to rats fed a linoleic acid (LA) diet was noted. Hepatic and serum triacylglycerol (TAG) concentrations were lowered in the CLA groups as compared to the control LA group. Decreased serum insulin and leptin levels were seen in the CLA groups. These results indicate that dietary CLA reduces both hepatic MTP activity and TAG content, and therefore reduces hepatic lipoprotein assembly and secretion.

Dietary linoleic acid suppresses gene expression of rat liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) and increases quinolinic acid in serum.

Hepatic ACMSD [EC4.1.1.45] plays a key role in regulating NAD biosynthesis from tryptophan. We previously reported that ingestion of polyunsaturated fatty acids by rats leads to a decrease in their hepatic ACMSD activity. We purified ACMSD and cloned cDNA encoding rat ACMSD. Therefore, in this study, we examined whether dietary linoleic acid altered ACMSD gene expression and its protein level. Moreover we measured the tryptophan catabolite quinolinic acid level in rats. In the rats fed with linoleic acid, ACMSD mRNA and its protein levels in the liver were strongly suppressed and serum quinolinic acid was significantly increased as compared with the rats fed on a fat-free diet. These results suggest that the transcription level of ACMSD is modulated by linoleic acids or their metabolites and probably there is an inverse relationship between ACMSD activity and the production of quinolinic acid converted from tryptophan.

Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid

It has been hypothesized that oxygen radicals generated by peroxidation of dietary linoleic acid may induce genetic damage and thereby increase cancer risk. We examined the effect of dietary supplementation with linoleic acid on the levels of oxidative DNA damage in peripheral lymphocytes and on the blood plasma antioxidant potential. Thirty volunteers received during 6 weeks either a high dose of linoleic acid (15 g/day), an intermediate dose of linoleic acid (7.5 g/day) or an isocaloric supplement without linoleic acid (15 g palmitic acid/day). After the intervention, no significant increase in oxidative DNA damage, measured as relative amounts of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) in DNA from peripheral lymphocytes, was observed in both high and intermediate linoleic acid-supplemented groups (increase of respectively 13 and 21%; P>0.05). Also, the differences between levels of oxidative DNA damage in the high or intermediate linoleic acid-supplemented group and the control group receiving palmitic acid (23% decrease) were not significant. Furthermore, no statistically significant differences were found between the total antioxidant capacities of blood plasma from the different experimental groups. Plasma levels of malondialdehyde, an important end-product of lipid peroxidation, were not increased after supplementation, nor were effects found on the plasma concentrations of retinol, α-tocopherol and β-carotene. Despite the experimental design that excludes several forms of bias introduced in studies based on modulation of dietary composition, our results provide no indication of increased oxidative stress or genetic damage as a result of increased dietary intake of linoleic acid. Therefore, we see no scientific basis to reconsider the public health policy to stimulate the intake of polyunsaturated fatty acids aimed at the reduction of coronary heart diseases.

Relationships between dietary fatty acid composition and either melting point or fatty acid profile of adipose tissue in broilers

Data on the fatty acid composition of the diet and that of the adipose tissue in broilers were collected from the literature. The linear regression between the dietary and the adipose tissue unsaturated to saturated fatty acids ratio (U/S ratio) was calculated because the U/S ratio of adipose tissue fat determines its melting point, which is an indicator of the consistency of poultry fat. For 54 data points from three different experiments, the linear correlation coefficient of the relationship between dietary and adipose tissue U/S ratio was 0.77. The regression equation for linoleic acid in adipose tissue as a function of dietary linoleic acid was calculated. The linoleic acid content of adipose tissue was expressed as weight percentage of total fatty acids. Intake was expressed as either weight percentage of total fatty acids or as energy percentage of total dietary metabolizable energy. The linear correlation coefficients were 0.68 and 0.78 as based on 116 or 91 data points from 15 or 12 different experiments. Significant correlations were also found for α-linolenic acid. The linoleic acid content of adipose tissue was found to be correlated ( r=0.87) for 25 data points with that in consumable broiler meat, which may affect serum cholesterol concentrations in humans. With the help of the regression formulas presented it may be possible to formulate broiler diets in relation to consumer health and product quality.

Dietary Docosahexaenoic Acid Levels Influence the Outcome of Arabinosylcytosine Chemotherapy in L1210 Leukemic Mice

: The purpose of this study was to investigate whether dietary supplementation with the n-3 fatty acid docosahexaenoic acid (DHA) in combination with arabinosylcytosine (AraC) chemotherapy could prolong the life expectancy of mice bearing L1210 leukemia. The four control diets included rodent chow, a diet containing 5% of a blended oil mimicking the fatty acid composition of rodent chow, and diets containing 5% or 10% fat with safflower oil as the main oil source. The two DHA-supplemented diets provided 1.5% or 3.5% DHA and 5% or 10% total fat, respectively. After tumor cell inoculation, mice were treated with AraC for 10 days. Mice fed the 5% safflower oil diet (30.1 ± 4.1 days), but not those fed the 10% safflower oil diet, survived longer than the chow-fed animals (22.1 ± 3.1 days, P = 0.05). The 1.5% DHA diet (average intake 1.8 g DHA/kg/day) was associated with a longer life span (33.3 ± 3.4 days, P < 0.01 vs. chow-fed) and no incidence of death due to drug toxicity. Further increasing DHA intake (4.5 g DHA/kg/day) resulted in shortened survival time (26.5 ± 2.0 days), increased circulating tumor cell burden, and lowered red blood cell concentrations. These data suggest that a modest level of dietary DHA or linoleic acid supplementation may improve the antineoplastic efficacy of AraC. However, overconsumption of DHA reverses the beneficial effect of DHA intake on drug sensitivity.

Influence of conjugated vs. conventional linoleic acid on liver metastasis and hepatic lipidperoxidation in BOP-induced pancreatic cancer in Syrian hamster

While conjugated linoleic acid (CLA) is regarded as an essential fatty acid with anticarcinogenic effects, conventional linoleic acid (LA) is reported to promote tumour growth in various experimental studies probably caused by high sensitivity to non-enzymatic lipid peroxidation. In order to evaluate the impact of dietary LA and CLA on liver metastasis and lipidperoxidation (LPO), 60 Syrian hamsters were injected with 10 mg N -nitrosobis-2-oxopropylamine (BOP)/kg body weight s.c. for 12 weeks. Animals were fed a special diet containing LA or CLA. The experiment was terminated after 24 weeks. Incidence, number and size of liver metastases were histologically determined. Furthermore, the activities of antioxidative enzymes and concentration of hepatic lipidperoxidation were measured intra- and extrametastatically. Incidence, number and size of liver metastases did not differ between the tumour groups. Otherwise, antioxidative enzyme activity of GSH-Px was higher in non-metastatic liver, while SOD activity and lipidperoxidation were increased in liver metastases. Conclusively there was no difference between the groups fed with LA and CLA according to the impact on liver metastasis in ductal pancreatic cancer.

Effect of dietary linoleic acid on the progression of chronic renal failure in rats.

The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean +/- SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 +/- 4 vs 126 +/- 13 mg%) and triglyceride (88 +/- 9 vs 132 +/- 19 mg%) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78% in RS and 100% in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27%) compared to RN (38%), tubulointerstitial damage was similar between CRF groups (RS = 1.91 +/- 0.2 and RN = 2.14 +/- 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days.

PCB-induced oxidative stress in endothelial cells: modulation by nutrients

AbstractThere is an increasing body of evidence suggesting that exposure to Superfund chemicals may have adverse consequences on many organ systems, as well as carcinogenic and atherogenic effects. This is particularly true for polyhalogenated aromatic hydrocarbons such as the polychlorinated biphenyls (PCBs). The vascular endothelium, which is constantly exposed to blood components including environmental contaminants, is extremely vulnerable to chemical insult as well as necrotic and apoptotic injury. Our recent studies suggest that certain PCBs, especially coplanar PCBs, can compromise normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways and subsequent proinflammatory events critical in the pathology of atherosclerosis and cardiovascular disease. Our findings suggest that an increase in the level of cellular oxidative stress is a significant event in PCB-mediated endothelial cell dysfunction and that nutrients can modulate PCB-induced oxidative stress and endothelial toxicity. We have demonstrated that the dietary fat linoleic acid, the parent unsaturated fatty acid of the omega-6 family, can increase endothelial dysfunction induced by selected PCBs, probably by contributing to oxidative stress and as the result of the production of toxic metabolites called leukotoxins. The subsequent imbalance in the overall cellular oxidant/antioxidant status can activate oxidative stress- or redox-sensitive transcription factors, which in turn promote gene expression for inflammatory cytokines and adhesion molecules, intensifying the inflammatory response and endothelial cell dysfunction. Our data also suggest that antioxidant nutrients such as vitamin E can protect against endothelial cell damage mediated by PCBs or polyunsaturated dietary fats by interfering with oxidative stress-sensitive and proinflammatory signaling pathways. The concept that nutrition can modify or ameliorate the toxicity of Superfund chemicals is provocative and warrants further study as the implications for human health are significant. The information from such studies could be used to develop dietary recommendations and nutritional interventions for populations at high risk for exposure to PCBs, including communities living near Superfund sites and those exposed via occupation or diet.

Selective inhibition of Δ-6 desaturase impedes intestinal tumorigenesis

Arachidonic acid is an important polyunsaturated fatty acid involved in cell signaling. It is derived primarily from dietary linoleic acid, and the rate-limiting step in its biosynthesis is the initial desaturation of linoleic acid via Δ-6 desaturase. Evidence suggests that downstream metabolic products of arachidonic acid, e.g. prostaglandins, are involved in colorectal cancer, but involvement of the biosynthetic pathway of arachidonic acid has not been previously investigated. In the present study, we report the effects of a novel selective Δ-6 desaturase inhibitor, SC-26196, on tumorigenesis in two in vivo models of intestinal cancer. SC-26196 treatment resulted in 36–37% fewer tumors in Apc Min/+ mice and 35% decrease in primary tumor size in nude mice bearing HT-29 human colon cancer cell xenografts ( P<0.05). As expected, SC-26196 treatment resulted in significantly higher linoleic acid levels in tissue phospholipids and lower levels of arachidonic acid. The effects on both tissue fatty acid composition and tumorigenesis in Apc Min/+ mice were abrogated by concomitant treatment with dietary arachidonic acid, indicating that the observed effects were due to interference with the biosynthetic pathway of arachidonic acid.

13C]Linoleic acid oxidation and transfer into milk in stunted lactating women with contrasting body mass indexes

The fat concentration of human milk is associated with maternal adiposity, but there is no clear understanding of the mechanisms controlling milk fat concentration. We evaluated the effect of postpartum body mass index (BMI; in kg/m(2)) on the metabolic distribution of an oral dose of [13C]linoleic acid in lactating women. Ten lactating women stratified by BMI (either <22.5 or >23.5) at 5 mo postpartum received orally 2.5 mg [13C]linoleic acid/kg body wt. Exhaled air, milk, and plasma samples were collected in relation to tracer administration. Linoleic acid was determined by gas chromatography. Dietary intake, serum, milk composition, [13C]linoleic acid enrichment in milk and plasma, and exhaled 13CO2 (by isotope ratio mass spectrometry) were assessed. Women with a higher BMI exhaled more 13CO2 than did women with a lower BMI (22.8 +/- 9.4% compared with 8.6 +/- 3.5% of dose, P < 0.03). Cumulated 72-h transfer of [13C]linoleic acid to milk was not significantly different between groups (14.8 +/- 6.5% compared with 17.7 +/- 6.7% of dose). Within the first 9 h after dose administration, 51.6 +/- 4.9% of the total isotope transfer into milk had passed in women with a higher BMI, but only 24.0 +/- 15.3% had passed in those with a lower BMI (P = 0.02). Women with a lower BMI, who were reputed as having less body fat, oxidized and secreted into milk less dietary linoleic acid within 12 h after tracer administration than did women with a higher BMI. In both groups, a large proportion of [13C]linoleic was retained in the maternal compartment, most likely fat tissue, in a slow turnover pool, and released slowly in later hours.