Alpha-linolenic Fatty Acid Research Articles

Association between plasma fatty acids and inflammatory markers in patients with and without insulin resistance and in secondary prevention of cardiovascular disease, a cross-sectional study

BackgroundProinflammatory biomarkers levels are increased among patients with cardiovascular disease, and it is known that both the presence of insulin resistance and diet may influence those levels. However, these associations are not well studied among patients with established cardiovascular disease. Our objective is to compare inflammatory biomarker levels among cardiovascular disease secondary prevention patients with and without insulin resistance, and to evaluate if there is any association between plasma fatty acid levels and inflammatory biomarker levels among them.MethodsIn this cross-sectional sub-study from the BALANCE Program Trial, we collected data from 359 patients with established cardiovascular disease. Plasma fatty acids and inflammatory biomarkers (interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, high sensitive C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor (TNF)-alpha) were measured. Biomarkers and plasma fatty acid levels of subjects across insulin resistant and not insulin resistant groups were compared, and general linear models were used to examine the association between plasma fatty acids and inflammatory biomarkers.ResultsSubjects with insulin resistance had a higher concentration of hs-CRP (p = 0.002) and IL-6 (p = 0.002) than subjects without insulin resistance. Among subjects without insulin resistance there was a positive association between stearic fatty acid and IL-6 (p = 0.032), and a negative association between alpha-linolenic fatty acid and pro-inflammatory biomarkers (p < 0.05). Among those with insulin resistance there was a positive association between monounsaturated fatty acids and arachidonic fatty acid and adiponectin (p < 0.05), and a negative association between monounsaturated and polyunsaturated fatty acids and pro-inflammatory biomarkers (p < 0.05), as well as a negative association between polyunsaturated fatty acids and adiponectin (p < 0.05). Our study has not found any association between hs-CRP and plasma fatty acids.ConclusionsSubjects in secondary prevention for cardiovascular disease with insulin resistance have a higher concentration of hs-CRP and IL-6 than individuals without insulin resistance, and these inflammatory biomarkers are positively associated with saturated fatty acids and negatively associated with unsaturated fatty acids.

Depressive symptoms and serum levels of polyunsaturated fatty acids omega-3 and omega-6 among college students from Northern Mexico

Previous studies suggest that low consumption as well as low serum levels of polyunsaturated fatty acids (PUFA) omega-3 and a high omega-6/omega-3 ratio may be implicated in the etiology of depressive disorders, however, epidemiologic evidence is inconclusive. To assess the relationship of serum levels of omega-3 fatty acids (docosahexaenoic [DHA], eicosapentaenoic [EPA], alpha-linolenic fatty acid [ALA]) and the omega-6 (arachidonic acid [AA])/EPA ratio with depressive symptoms among Mexican college students. A cross-sectional study that included 60 male and female participants (ages 18 to 24 years) with serum levels of EPA, DHA, ALA and AA. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression (CES-D) scale validated for Mexican students. Linear regression was used to assess the relationship between depressive symptoms and serum PUFA omega-3 and omega-6. Serum levels of EPA, DHA and EPA/DHA ratio were not related to depressive symptoms, high serum ALA was related with lower depressive symptoms before and after covariate adjustment; however, these results were not statistically significant. Among women, 1% increase in EPA resulted in 5.5. (p = 0.57) increase in the depressive scale scores while 1% increase in ALA resulted in 6.7 decrease (p = 0.39) in the scores. Our results did not confirm the relationship of serum levels of PUFA omega-3 and omega-6/omega-3 ratio with depressive symptoms; the negative correlation of serum ALA with depressive symptoms remains to be confirmed in prospective studies.

Fatty Acids Profile of Coffea arabica L. Resistant to Leaf Rust Grown in Two Environments of Minas Gerais, Brazil

The quality of the coffee drink is defined by its sensorial attributes which are developed through the chemical predecessors found on raw grains. Due to this relation, this present work had a goal evaluating the sensorial characteristics of resistant coffee cultivars to leaf rust for the production of specialty coffee and correlate them with the profile of fatty acids present on raw grains, enabling the distinction of cultivars in two environments of Minas Gerais. For this purpose, seven cultivars of Coffea arabica resistance to leaf rust were evaluated and two susceptible cultivars, in two growing environments: Lavras, in the South of Minas Gerais and Patrocínio, in the Cerrado of Minas Gerais. The C16:0, C16:1, C18:0, C18:1, C18:2 w-6, C18:3 w-3 fatty acids common in coffee grains, were identified in the cultivars. The presence of an acid uncommon in coffee grains, the gamma linolenic acid (C18:3 w-6, GLA) was also detected. The palmitic and alpha linolenic fatty acids presented correlation with the sensorial quality of the drink. The linoleic, palmitic, alpha linolenic and gamma linolenic fatty acids were capable to differentiate the Patrocinio and Lavras environments. The profile of the fatty acids permitted differentiate the leaf rust resistant cultivars, the environments as also the interaction between these two matters related to the sensorial quality.

Insufficient intake of alpha-linolenic fatty acid (18:3n-3) during pregnancy and associated factors

ABSTRACT Objective: To analyze alpha-linolenic fatty acid intake in two cohorts of pregnant women, and to identify factors associated with alpha-linolenic acid intake. Methods: This is a cohort study involving pregnant women with low obstetric risk (N=353) in public health system from a municipality of São Paulo state, Brazil. In each trimester, two 24-hour food recalls were collected. Descriptive analyses of dietary lipid profiles were performed, followed by a multiple comparison test. According to the trimester of pregnancy, differences were assessed using the mean difference test. To evaluate the adequacy of linoleic fatty acid and alpha-linolenic acid intake, the adequate intake test was used. The association between alpha-linolenic acid intake adequacy and maternal characteristics was investigated using a binary logistic regression model. Results: Total lipids intake and the percentage contribution to dietary energy met recommended levels. One-third of the diets demonstrated a lower than daily recommended intake of alpha-linolenic acid. Overweight pregnant women were twice as likely to have inadequate alpha-linolenic acid intake. Pregnant women from a more disadvantaged socioeconomic situation had greater risks of inadequate intake. Conclusion: Over-intake of lipids is not problematic, but quality is an issue, with one third of the pregnant women and their fetuses exposed to adverse effects due to low intake of omega-3 fatty acids, indicating important nutritional vulnerability in this population.

Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

ABSTRACTObjective: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8+) subpopulation, and increased TNF-α production. Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.

Quantitative Spatiotemporal Chemical Profiling of Individual Lipid Droplets by Hyperspectral CARS Microscopy in Living Human Adipose-Derived Stem Cells.

There is increasing evidence showing that cytosolic lipid droplets, present in all eukaryotic cells, play a key role in many cellular functions. Yet their composition at the individual droplet level and how it evolves over time in living cells is essentially unknown due to the lack of suitable quantitative nondestructive measurement techniques. In this work, we demonstrate the ability of label-free hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy, together with a quantitative image analysis algorithm developed by us, to quantify the lipid type and content in vol/vol concentration units of individual lipid droplets in living human adipose-derived stem cells during differentiation over 9 days in media supplemented with different fatty acids. Specifically, we investigated the addition of the polyunsaturated linoleic and alpha-linolenic fatty acids into the normal differentiation medium (mostly containing monounsaturated fatty acids). We observe a heterogeneous uptake which is droplet-size dependent, time dependent, and lipid dependent. Cells grown in linoleic-acid-supplemented medium show the largest distribution of lipid content across different droplets at all times during differentiation. When analyzing the average lipid content, we find that adding linoleic or alpha-linolenic fatty acids at day 0 results in uptake of the new lipid components with an exponential time constant of 22 ± 2 h. Conversely, switching lipids at day 3 results in an exponential time constant of 60 ± 5 h. These are unprecedented findings, exemplifying that the quantitative imaging method demonstrated here could open a radically new way of studying and understanding cytosolic lipid droplets in living cells.

Crop year effects on seed yields, growing cycle length, and chemical composition of chia (Salvia hispanica L) growing in Ecuador and Bolivia

Chia (Salvia hispanica L.) is an annual summer herb, and a member of the Lamiaceae family. The present study was conducted between 2007-2010 period, on seeds commercially grown in Bolivia (Sub-Humid Chaco Ecosystem) and Ecuador (Tropical Forest Ecosystem). The crop year effect on the growing cycle length, seed yield, seed’s protein content, lipid content, and fatty acids profile, was determined. The mean growing cycle length ranged from 108-d at Sub-Humid Chaco Ecosystem to 113-d at the Tropical Forest Ecosystem. The Tropical Forest Ecosystem had higher maximum and average yields at each year crop, than the Sub-Humid Chaco Ecosystem. Overall, the seed from the Tropical Forest Ecosystem showed significant (P<0.05) higher content of alpha-linolenic fatty acid comparing to that from the Sub-Humid Chaco Ecosystem. The seeds from the Tropical Forest Ecosystem showed the lowest significant (P<0.05) linoleic and oleic fatty acid concentrations. The n-6:n-3 ratio was significantly (P<0.05) lower in oils from seeds grown in Ecuador compared to that of seeds grown in Bolivia. Regression analysis were performed for alpha-linolenic vs. oleic and linoleic fatty acid contents. Analysis using combined data of fatty acids from all four years and from both ecosystems revealed that alpha-linolenic fatty acid content was negatively correlated with its precursors –oleic (R2= 0.77, P < 0.0005), and linoleic (R2= 0.92, P < 0.0005) fatty acids. Compared to chia seeds grown in Bolivia, the chia seeds grown in Ecuador showed more stability and a significant (P<0.05) higher alpha-linolenic fatty acid content.

CONSUMPTION OF OMEGA- 3 FATTY ACIDS AND DEPRESSIVE SYMPTOMS IN COLLEGE STUDENTS FROM SONORA, MEXICO

recent studies suggest that low serum levels of polyunsaturated fatty acids omega-3 are associated with a higher prevalence of depression. to evaluate whether low consumption of Omega-3 fatty acids is associated with a higher prevalence of depressive symptoms in a sample of college students from the Northwest of Mexico, and to assess the potential effect modification by alcohol consumption. we conducted a cross-sectional study in a sample of 706 college students (males and females) aged 18 to 24. The presence of depressive symptoms was identified with the Depression Scale of the Center for Epidemiologic Studies (CES-D), using a cutoff point of ≥ 24. The intake of omega-3 was obtained by a food frequency questionnaire validated for Mexican population. We estimated the weekly intake of alpha-linolenic fatty acid (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) derived from the diet in mg/g of food. The association between omega-3 from diet and the presence of depressive symptoms was assessed using logistic regression models adjusted for potential confounders. 67% of the participants were females; 16.6% were classified as having depressive symptoms. A low intake of ALA and EPA + DHA was not associated with depressive symptoms before and after adjusting for confounders. Median levels of ALA (from nuts only) were significantly lower among those with depressive symptoms compared to those without these symptoms. in this population of Mexican college students, a low intake of omega-3 fatty acids was not associated with depressive symptoms. The potential association between nut consumption and depressive symptoms deserve more attention.

Diet may lessen heart disease as SGA infants grow up

The fact that people born small for gestational age (SGA) have increased risk of having cardiovascular disease is well described. Advances in the care of these infants have resulted in the majority of them surviving into adulthood only to suffer from premature atherosclerosis and elevations in blood pressure. Currently little is known about prevention strategies that may be helpful in reducing this increased risk. Dietary omega-3 fatty acids may be useful in reducing this problem in SGA people as the age but studies to date have been limited by size and design. In this issue of The Journal, Skilton et al report the results of the STRIP study which followed 115 infants who were born SGA and recorded their food records, blood pressure, and aortic intima-media wall thickness every 3-12 months for 19 years. The results suggest that long-term dietary alpha-linolenic acid intake during childhood is associated with improved vascular health and blood pressure in people who are born SGA. The results of this study are promising; however, randomized trials with evaluations of other possible dietary components will be needed before firm conclusions and recommendations can be made. This study is an excellent start. Article page 1252▶ The Association of Dietary Alpha-Linolenic Acid with Blood Pressure and Subclinical Atherosclerosis in People Born Small for Gestational Age: The Special Turku Coronary Risk Factor Intervention Project StudyThe Journal of PediatricsVol. 166Issue 5PreviewTo determine whether dietary alpha-linolenic (omega-3) fatty acid intake is associated with lower blood pressure and aortic intima-media thickness (IMT) in people born small for gestational age (SGA). Full-Text PDF

The Association of Dietary Alpha-Linolenic Acid with Blood Pressure and Subclinical Atherosclerosis in People Born Small for Gestational Age: The Special Turku Coronary Risk Factor Intervention Project Study

To determine whether dietary alpha-linolenic (omega-3) fatty acid intake is associated with lower blood pressure and aortic intima-media thickness (IMT) in people born small for gestational age (SGA). Participants were recruited at age 6 months and followed up every 6-12 months until age 19 years. Blood pressure and food records were assessed at each visit. A total of 1009 participants had at least one blood pressure measure and complete birth weight and gestational age data, including 115 (11%) born SGA (birth weight≤10th percentile). Aortic IMT was assessed by ultrasound at 19 years (n=413). Analysis was by linear mixed models and multivariable linear regression. Children born SGA had greater systolic and pulse pressure from age 14 years onwards. In those born SGA, systolic blood pressure was 2.1 mm Hg lower ([95% CI 0.8-3.3]; P=.001) and pulse pressure 1.4 mm Hg lower ([95% CI 0.3-2.4]; P=.01), per exponential increase in alpha-linolenic acid (ALA) intake; weakened by adjustment for anthropometric measures. Long-term ALA intake was inversely associated with aortic IMT at 19 years in those born SGA (-0.30 mm [95% CI -0.52, -0.08] per exponential greater ALA intake; P=.008), independent of other dietary and anthropometric factors. Long-term dietary ALA intake during childhood is associated with improved vascular health in people born SGA.

Incorporation of conjugated linoleic and alpha linolenic fatty acids into Pimedolus maculatus fillets

The objective of this study was to investigate the fatty acid composition of Pimedolus maculatus fillets of fish fed with different diets. The fish were submitted to an adaptation period (over 30 days) and fed only a control diet (diet I). After this period, the fish were divided into two groups: one group received a diet enriched with flaxseed oil (diet II), and the other received a diet enriched with conjugated linoleic acid (CLA) (diet III). Subsequent collections were undertaken after 25 and 50 days. Compared to the control samples, fish fed diet II showed an increase in concentrations of total fatty acid omega-3 (n-3) in the fillets, with an improvement ratio of n-6/n-3. The incorporation of CLA into fish fed diet III was successful. Supplementing the diet of Pimedolus maculatus with CLA and flaxseed oil led to improvements in nutritional quality and fatty acid profile of the fish fillets.

Antioxidant capacity and chemical composition in seeds rich in omega-3: chia, flax, and perilla

The chemical composition and antioxidant capacity of five seeds, chia, golden flax, brown flax, white perilla, and brown perilla, were determined. The chemical properties analyzed included moisture, ash, crude protein, carbohydrates, total lipids, fatty acids, and antioxidant capacity (ABTS•+, DPPH•, and FRAP). The results showed the highest amounts of protein and total lipids in brown and white perilla. Perilla and chia showed higher amounts of alpha-linolenic fatty acid than those of flaxseed varieties, ranging between 531.44 mg g-1 of lipids in brown perilla, 539.07 mg g-1 of lipids in white perilla, and 544.85 mg g-1 of lipis in chia seed. The antioxidant capacity of the seeds, evaluated with ABTS•+, DPPH• , and FRAP methods, showed that brown perilla had greater antioxidant capacity when compared with white perilla, flax, and chia seeds.

Adherence to the European food safety authority's dietary recommendations and colorectal cancer risk

The European Food Safety Authority (EFSA) recently published dietary guidelines for the intakes of carbohydrates, fiber, fats and water. We evaluated their role on the risk of a specific disease, known to be related to diet. We used data from an Italian case-control study including 1953 colorectal cancer (CRC) cases and 4154 controls. We developed a so-called EFSA index summing up 1 point for adherence to each EFSA guideline. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of CRC and its subsites were derived from unconditional multiple logistic regression models, for both the index and its components. When each EFSA index component was analyzed separately, we found significant increased risks of CRC for non adherence to the guidelines on linoleic (OR=1.20, 95% CI, 1.07-1.36) and alpha-linolenic fatty acids (OR=1.19, 95% CI, 1.06-1.34). When all the guidelines were included in the same model, no significant association emerged. Compared with minimal adherence, the ORs of CRC for subsequent EFSA index scores were 1.03 (95% CI, 0.72-1.47), 1.05 (95% CI, 0.75-1.48), 1.04 (95% CI, 0.81-1.60), 0.99 (95% CI, 0.69-1.43), and 1.04 (95% CI, 0.67-1.61). No significant association emerged for colon and rectal cancer separately, and for males and females. Overall adherence to the EFSA dietary guidelines is not associated to colorectal, colon and rectal cancer risk in our population. Adherence to guidelines on linoleic and alpha-linolenic fatty acids may have a modest beneficial role on CRC risk.

Differential effects of linoleic and alpha-linolenic fatty acids on spatial and temporal mitochondrial distribution and activity in bovine oocytes

Using specific stains and confocal microscope imaging, the patterns of mitochondrial distribution, mitochondrial inner membrane potential and reactive oxygen species (ROS) levels during bovine oocyte maturation were determined in the presence or absence of physiological concentrations of linoleic acid (LA; 100µM) or α-linolenic acid (ALA; 50µM). Mitochondrial distribution in control oocytes at 0h was mainly peripheral and changed to a diffused pattern after 1h of culture; this was maintained up to 24h. Mitochondrial clusters were observed during the early hours of maturation (1-4h); the majority of these were arranged in perinuclear fashion. LA supplementation resulted in: (1) delayed redistribution of the mitochondria from a peripheral to a diffuse pattern and a decreased percentages of oocytes showing perinuclear mitochondrial clusters, (2) decreased mitochondrial inner membrane potential at 1 and 24h compared with the control and (3) higher ROS levels, associated with a lower nuclear maturation rate. In contrast, ALA supplementation had no effect on mitochondrial distribution and activity and decreased ROS levels compared with the control; this was associated with an increased nuclear maturation rate. In conclusion, LA induced alterations in mitochondrial distribution and activity as well as increasing ROS levels, which mediate, at least in part, the inhibitory effect on oocyte maturation.

Selected plasma fatty acid levels in subsistence fed sled dogs along the Yukon River: a pilot study for biomonitoring

ABSTRACTThe introduction of the ‘western diet’ marked a decline in omega–3 fatty acids rich foods and a concurrent increase in saturated and omega–6 fatty acids that persists today. Historically, circumpolar people have had a low incidence of obesity, diabetes and cardiovascular disease and this has been largely attributed to polyphenolic compounds and omega–3 fatty acids offered from subsistence foods. In this report, we studied sled dogs as an Arctic sentinel species for monitoring the effect of a changing diet on lipid profiles along the Yukon River. Subsistence fed village sled dogs along the Yukon River, maintained largely on salmon were compared with a control kennel maintained on commercial food. Profiles showed higher levels for long chain omega–3 fatty acids in village subsistence fed dogs compared to control dogs and an opposite trend for omega–6 fatty acids, establishing baseline levels for follow up studies. A comparison with data for previously published mercury levels from the same cohort of dogs revealed a positive correlation with alpha–linolenic fatty acid and a negative correlation with linoleic fatty acid. Food and nutritional security is a concern in the Arctic as the impacts of climate change and transport of contaminants become obvious. This study supports not only the nutritional value of a subsistence diet but also the utility of sled dogs as a sentinel for human dietary change.

The Seed's Protein and Oil Content, Fatty Acid Composition, and Growing Cycle Length of a Single Genotype of Chia (Salvia hispanica L.) as Affected by Environmental Factors

As a botanical source, variability in chia seed composition could be expected between growing locations, and between years within a location, due to genotype and environment effects as well genetic x environment's interactions. The objective of the present study was to determine the location effect on the growing cycle length, and seed's protein content, lipid content, and fatty acid profiles, of a single chia genotype. Seeds of chia genotype Tzotzol grown on eight sites in five different ecosystems were tested. One site was in Argentina, in the Semi-Arid Chaco ecosystem (T(5)); one was in Bolivia, in the Sub-Humid Chaco ecosystem (T(4)); and six in Ecuador, one in the Coastal Desert (T(3)), two on the Tropical Rain Forest (T(2)), and three in the Inter-Andean Dry Valley ecosystem (T(1)). Seeds from plants grown in T(4) and in T(3) contained significantly (P <0.05) more protein percentage than did seeds from the other three ecosystems. No significant (P <0.05) differences in protein content were found between T(3) and T(4), and between T(1), T(2), and T(5). Seeds from T(1) and T(5) ecosystems, with 33.5 and 32.2%, respectively, were the numerically highest oil content producers, but their results were only significantly (P <0.05) higher when compared with the T(2) seeds. Significant (P <0.05) differences in palmitic, stearic, oleic, linoleic and alpha-linolenic fatty acids between oils from seeds grown in different ecosystems were detected, however. Oil of seeds grown in the T(3) ecosystem had the palmitic, stearic and oleic fatty acids' highest contents. Palmitic and oleic fatty acid levels were significantly (P <0.05) higher when were compared to that of seeds grown in the T(1) ecosystem, and stearic when was compared to that of seeds grown in the T(5) ecosystem; omega-6 linoleic fatty acid content was significantly (P <0.05) lower in oils of seeds produced in T(1), and T(2) than in those produced in T(3), T(4), and T(5) ecosystems; omega-3 alpha-linolenic fatty acid content was significantly (P <0.05) higher in seeds produced in T(1), than in those produced in T(3), T(4), and T(5), but not in those produced in T(2).

Antioxidant Activity and Isoflavone Content of Maryland-Grown Soybeans Low in Saturated And/or Alpha-Linolenic Fatty Acids

After the poster presentation, the viewer will be able to articulate what is known about the antioxidant capacity of soybeans with altered lipid profiles in relation to soybeans with normal lipid profiles.

Problems with the assessment of dietary fat in prostate cancer studies.

The authors conducted a detailed review of studies on the association between prostate cancer and total dietary fat along with specific fatty acids. Overall, the 29 studies reporting actual dietary fat levels in grams of fat were heterogeneous, suggesting that pooling of the relative risks may be inappropriate. Heterogeneity was also seen by study design. More specifically, although the pooled estimate for prostate cancer and an increase of 45 g in total fat consumption per day was small (relative risk = 1.2), heterogeneity between studies was large, and the association was not supported by specific fatty acids. The strongest association was found among the five extremely inconsistent studies of alpha-linolenic fatty acid. The associations with advanced prostate cancer were more homogeneous and suggest a relation with total and saturated fat but none with specific fatty acids. This review highlights the inconsistent way in which total dietary fat and specific fatty acids have been measured and reported across epidemiologic studies of prostate cancer. The heterogeneity between studies was large, possibly because of the variation in the dietary instruments used and the corresponding databases (nondifferential misclassification), recall bias, differing case definitions, residual confounding, or potential selection bias in different studies.

Overexpression and hyperactivity of breast cancer-associated fatty acid synthase (oncogenic antigen-519) is insensitive to normal arachidonic fatty acid-induced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal alpha-linolenic and gamma-linolenic fatty acids: a novel mechanism by which dietary fat can alter mammary tumorigenesis.

Activity and expression of fatty acid synthase (FAS), a critical enzyme in the de novo biosynthesis of fatty acids in mammals, is exquisitely sensitive to nutritional regulation of lipogenesis in liver or adipose tissue. Surprisingly, a number of studies have demonstrated hyperactivity and overexpression of FAS (oncogenic antigen-519) in a biologically aggressive subset of human breast carcinomas, suggesting that FAS-dependent neoplastic lipogenesis is unresponsive to nutritional regulation. We have assessed the role of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on the enzymatic activity and protein expression of tumor-associated FAS in SK-Br3 human breast cancer cells, an experimental paradigm of FAS-overexpressing tumor cells in which FAS enzyme constitutes up to 28%, by weight, of the cytosolic proteins. Of the omega-3 PUFAs tested, alpha-linolenic acid (ALA) dramatically reduced FAS activity in a dose-dependent manner (up to 61%). omega-3 PUFA docosahexaenoic acid (DHA) demonstrated less marked but still significant inhibitory effects on FAS activity (up to 37%), whereas eicosapentaenoic acid (EPA) was not effective. Of the omega-6 fatty acids tested, gamma-linolenic acid (GLA) was the most effective dose-dependent inhibitor of FAS activity, with a greater than 75% FAS activity reduction. Remarkably, omega-6 PUFAs linoleic acid (LA) and arachidonic acid (ARA), suppressors of both hepatic and adipocytic FAS-dependent lipogenesis, had no significant inhibitory effects on the activity of tumor-associated FAS in SK-Br3 breast cancer cells. Western blotting studies showed that down-regulation of FAS protein expression tightly correlated with previously observed inhibition of FAS activity, suggesting that ALA-, DHA-, and GLA-induced changes in FAS activity resulted from effects at the protein level. We investigated whether the FAS inhibitory effect of GLA and omega-3 PUFAs correlated with a cytotoxic effect related to a peroxidative mechanism. Measurement of cell viability by MTT assay indicated a significant cellular toxicity after ALA and GLA exposures. Furthermore, we observed a significant correlation between the ability of PUFAs to repress FAS and cause cell toxicity. In the presence of anti-oxidants (vitamin E), ALA and GLA dramatically lost their ability to inhibit FAS activity. Interestingly, a combination of ALA and GLA was FAS inhibitory in an additive manner, and this FAS repression was only partially reversible by vitamin E. In examining the molecular mechanisms underlying resistance of breast cancer-associated FAS to normal dietary fatty acid-induced suppression, a dramatic decrease of FAS accumulation was found after exposure of SK-Br3 cells to mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (MAPK ERK1/2) inhibitor U0126, phosphatidylinositol-3'-kinase (PI-3'K) blocker LY294002, and/or anti-HER-2/neu antibody trastuzumab. Interestingly, a long-term exposure to pharmacological inhibitors of FAS activity cerulenin [(2S,3R) 2,3-epoxy-4-oxo-7E,10E-dodecadienamide] or C75 also resulted in a significant reduction of FAS accumulation. These data indicate that: a) GLA- and omega-3 PUFA-induced repression of tumor-associated FAS may result, at least in part, from a non-specific cytotoxic effect due to peroxidative mechanisms; b) alternatively, GLA and omega-3 PUFAs have a suppressive effect on FAS expression and activity that can result in the accumulation of toxic fluxes of the FAS substrate malonyl-CoA; c) GLA- and/or omega-3 PUFA-induced repression of tumor-associated FAS may represent a novel mechanism of PUFA-induced cytotoxicity clinically useful against breast carcinomas carrying overexpression of FAS enzyme; d) fundamental differences in the ability of FAS gene to respond to normal fatty acid's regulatory actions in lipogenic tissues may account for the observed extremely high levels of FAS in breast carcinoma; and e) FAS overexpression in SK-Br3 breast cancer cells is driven by increases in HER-2/neu signaling, acting in major part through a constitutive downstream art through a constitutive downstream activation of the MAPK ERK1/2 and PI-3'K/AKT transduction cascades.

Chia seed (Salvia hispanica L.) as an omega-3 fatty acid source for broilers: influence on fatty acid composition, cholesterol and fat content of white and dark meats, growth performance, and sensory characteristics

Five thousand four hundred, 1-d-old, male, Ross 308, broiler chicks were fed for 49 d to compare diets containing 10 and 20% chia (Salvia hispanica L.) seed to a control diet. Cholesterol content, total fat content, and fatty acid composition of white and dark meats were determined at the end of the trial. A taste panel assessed meat flavor and preference. Cholesterol content was not significantly different among treatments; however, the 10% chia diet produced a lower fat content in the dark meat than did the control diet. Palmitic fatty acid content was less in both meat types when chia was fed, with differences being significant (P < 0.05), except for the white meat and the 20% chia diet. alpha-Linolenic fatty acid was significantly higher (P < 0.05) in the white and dark meats with the chia diets. Chia significantly lowered the saturated fatty acid content as well as the saturated:polyunsaturated fatty acid and omega-6:omega-3 ratios of the white and dark meats compared to the control diet. No significant differences in flavor or preference ratings were detected among diets. Body weight and feed conversion were significantly lower with the chia diets than with the control, with weight reductions up to 6.2% recorded with the 20% chia diet.