Contribution of n-3 Long-Chain Polyunsaturated Fatty Acids to the Prevention of Breast Cancer Risk Factors.
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ABSTRACT:
SUBMITTER: Fodil M
PROVIDER: S-EPMC9265492 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long chain polyunsaturated fatty acids (PUFAs) are important structural components of cellular membranes and are converted into eicosanoids which serve various biological roles. The most common dietary n-6 and n-3 PUFAs are linoleic acid and ?-linoleic acid, respectively. These 18-carbon chain fatty acids undergo a series of desaturation and elongation steps to become the 20-carbon fatty acids arachidonic acid and eicosapentaenoic acid, respectively. Evidence from genome wide association studies has consistently demonstrated that plasma and tissue levels of the n-6 long-chain PUFA arachidonic acid and to a lesser extent the n-3 long-chain PUFA eicosapentaenoic acid, are strongly influenced by variation in fatty acid desaturase-1,-2, and elongation of very long chain fatty acid genes. Studies of functional variants in these genes, as well as studies in which desaturase activity has been indirectly estimated by fatty acid product-to -precursor ratios, have suggested that endogenous capacity to synthesize long-chain PUFAs may be associated with metabolic diseases such as diabetes mellitus. Interventional studies are starting to tease out the complicated relationship between dietary intakes of specific fatty acids, variation in desaturase and elongase genes and tissue levels of long chain PUFAs. Thus future studies of dietary PUFA interventions designed to reduce inflammatory and metabolic diseases will need to carefully consider how an individual's genetically-determined endogenous long-chain PUFA synthesis capacity might modify therapeutic response.
| S-EPMC4574498 | biostudies-literature
Project description:Thraustochytrids have been isolated from different aquatic systems; however, few studies have reported their occurrence in Antarctica. In this study, 13 strains close to strains belonging to the genera Oblongichytrium, Thraustochytrium, and Aurantiochytrium were isolated from seawater samples collected near the Antarctic Base Professor Julio Escudero (S 62°12'57' E 58°57'35?). Docosahexaenoic acid (DHA) was found in the total lipids of all the isolates; DHA content of the biomass (dry weight) varied between 3.3 and 33 mg/g under the growth conditions for isolation. Five of the Antarctic thraustochytrids were able to accumulate lipids at levels higher than 20% w/w. Two strains, RT2316-7 and RT2316-13, were selected to test the effect of the incubation temperature (at 5°C for 14 days and at 15°C for 5 days). Incubation temperature had little effect on the lipid content and biomass yield; however, its effect on the fatty acid composition was significant (p < .05). The low incubation temperature favored the accumulation of eicosapentaenoic acid (EPA), palmitic acid and stearic acid in the total lipids of RT2316-7. Percentage of EPA, DHA and the omega-6 fatty acid dihomo-?-linolenic acid of total fatty acids of RT2316-13 was higher at the low incubation temperature. RT2316-13 accumulated the highest lipid content (30.0 ± 0.5%) with a carbon to nitrogen mass ratio equal to 16.9. On the contrary, lipid accumulation in RT2316-7 occurred at high concentration of the nitrogen sources (monosodium glutamate or yeast extract). The capability to accumulate lipids with a fatty acid profile that can be tuned through cultivation temperature make the Antarctic thraustochytrid RT2316-13 a candidate for the production of lipids with different uses.
| S-EPMC6957410 | biostudies-literature
Project description:Very-long-chain polyunsaturated fatty acids (VLCPUFA; C24-38) that contain between 5-6 unsaturated double bonds are a unique class of PUFA that are primarily found in the retina, brain and testes. VLCPUFA appear to have important biological roles that cannot be fulfilled by the more common shorter-chain PUFA, but the lack of a suitable dietary source of VLCPUFA have limited research in this field. Typically, fish oils contain only a small amount of VLCPUFA (<1%, w/w), but we were able to produce a fish oil concentrate that contained over 40% by weight of n-3 VLCPUFA, with chain lengths between C24 and C28. A single-dose oral gavage of the VLCPUFA-oil in C57BL/6J mice resulted in a 9-fold increase in plasma levels of C24:5 n-3 by 2 hours. This was followed by a 70% increase in the retinal level of C24:5 n-3 after 8 hours from the gavage. Long-term (8-week) dietary supplementation with 1% or 5% (w/w) of VLCPUFA-oil in chow diet did not cause any adverse changes in the plasma chemistry profile or evidence of histologic injury to multiple tissues. It was found to alter the lipid composition of the liver, brain and eye in 11-month-old C57BL/6J mice. The VLCPUFA supplementation also caused favorable cardiometabolic changes by lowering plasma glucose, insulin, cholesterol and triglyceride levels. Furthermore, mice treated with the VLCPUFA oil had improved electroretinography response and visual performance after 15 consecutive days of oral gavage. Transcriptomic analysis of treated mice revealed significant alternation in genes involved in PPAR signaling pathways. Further in vitro studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 n-3 are potent agonists for both PPAR-alpha and gamma. In conclusion, the multiple potential beneficial effects of fish-derived VLCPUFA-oil on eye health and cardiometabolic risk in mice support future efforts to develop VLCPUFA-oil into a novel therapy.
2023-12-14 | GSE221559 | GEO
Project description:Macular degeneration is a progressive, bilateral eye disorder that damages the macula of the human eye. The most common form of macular degeneration is age-related macular degeneration (AMD), which is the leading cause of irreversible blindness in people older than 50 years in developed countries. Autosomal dominant Stargardt disease-3 (STGD3) is an inherited macular dystrophy that has clinical features similar to dry AMD, but occurs at a much earlier age. It is caused by a mutation in the elongation of very-long-chain fatty acids-like 4 (ELOVL4) gene, which is responsible for encoding the elongase enzyme that converts shorter chain fatty acids into C28-C38 very long-chain polyunsaturated fatty acids (VLCPUFAs, total number of carbons ?24). Diets rich in long-chain polyunsaturated fatty acids (LCPUFAs) have inverse associations with the progression of AMD and STGD3, and a deficiency in retinal LCPUFAs and VLCPUFAs has been detected in AMD retinas and STGD3 animal models. This article systematically summarizes the roles of LCPUFAs and VLCPUFAs in AMD and STGD3, and discusses future research directions.
| S-EPMC4196247 | biostudies-literature
Project description:In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA-derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the "return to homeostasis" process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega-6 fatty acid ARA appears increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega-6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC-PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega-3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC-PUFAs. More specifically this review focuses on the dietary omega-3 LC-PUFAs and the omega-6/omega-3 balance, in a wide range of inflammation disorders, including autoimmune diseases. This review suggests that the current recommendations of consumption and/or supplementation of omega-3 FAs are specific to particular groups of age and physiological status, and still need more fine tuning for overall human health and well being.
| S-EPMC5532176 | biostudies-other
Project description:PurposeIt is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts.MethodsWe searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations.ResultsA total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages.ConclusionIn this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.
| S-EPMC7900030 | biostudies-literature
Project description:Retinal long-chain PUFAs (LC-PUFAs, C(12)-C(22)) play important roles in normal human retinal function and visual development, and some epidemiological studies of LC-PUFA intake suggest a protective role against the incidence of advanced age-related macular degeneration (AMD). On the other hand, retinal very long-chain PUFAs (VLC-PUFAs, C(n>22)) have received much less attention since their identification decades ago, due to their minor abundance and more difficult assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are associated with rare forms of inherited macular degenerations have refocused attention on their potential roles in retinal health and disease. We thus developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then applied them to the study of their changes in ocular aging and AMD. With ocular aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid peaked in middle age. Compared with age-matched normal donors, docosahexaenoic acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs, and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.
| S-EPMC2952562 | biostudies-literature
Project description:Adolescent pregnancy increases risk of adverse perinatal outcomes. Placental delivery of long-chain polyunsaturated fatty acids (LCPUFA) is essential for fetal growth and development. In this pilot study, we aimed to assess maternal and fetal status of fatty acids (FA) measured at birth and the expression of key genes involved in FA uptake, transport and metabolism in the placenta of fifteen adolescents and fifteen adults. FA were quantified by gas-liquid chromatography. Placental expression of FA transporters was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and peroxisome proliferator-activated receptor gamma (PPAR?) was quantified by Western Blot. Adolescents had lower docosahexaenoic acid (DHA, 22:6 n-3) and total n-3 FA levels in maternal erythrocytes and placenta, but these were not different in fetal erythrocytes. Arachidonic acid (AA, 20:4 n-6) concentration was increased in placenta but lower in fetal circulation. Plasma membrane fatty acid binding protein (FABPpm) and fatty acid transport protein (FATP) 4 mRNA expressions were not different, however FATP1, fatty acid translocase (FAT/CD36) and fatty acid binding protein 3 (FABP3) mRNA and PPAR? protein levels were decreased in placenta of adolescents. Despite significant downregulation of FATP1, CD36 and FABP3, there was only a modest decrease in LCPUFA (10%) and AA (12%) and no difference in DHA content in cord blood, suggesting that FA transfer to the fetus was partially protected by other factors in adolescents from this cohort.
| S-EPMC5852796 | biostudies-literature
Project description:To investigate whether children who consumed infant formula supplemented with long-chain polyunsaturated fatty acids (LCPUFAs) had a more favourable cardiovascular profile than children who consumed formula without these fatty acids, we used the Wheezing Illnesses Study Leidsche Rijn, a birth cohort that included 2,468 newborns between 2001 and 2014. Data on infant feeding were obtained by questionnaires. At age 5, blood pressure, carotid intima-media thickness (CIMT), and carotid distension were measured. We used multivariable linear regression analysis to compare levels of cardiovascular markers in formula-fed children born before and after the LCPUFA supplementation. To account for secular trends, we compared levels of cardiovascular markers in a control group of breastfed children from the same cohort born before and after the supplementation. Formula-fed children born after the LCPUFA supplementation (n = 48) had no different systolic blood pressure (-2.58 mmHg, 95% confidence interval, CI [-5.5, 0.30]), diastolic blood pressure (-0.13 mmHg, 95% CI [-2.3, 2.1]), or carotid distension (24.8 MPa-1 , 95% CI [-47.1, 96.6]) and had a higher CIMT (18.6 ?m, 95% CI [3.7, 33.5]) than formula-fed children born before the supplementation (n = 163). In the control group, children born after the LCPUFA supplementation (n = 98) had no different systolic- or diastolic-blood pressure, or CIMT, and a higher carotid distension than children born before the supplementation (n = 142). In conclusion, children who consumed infant formula supplemented with LCPUFAs did not have a more favourable cardiovascular profile in early childhood than children who consumed formula without LCPUFAs.
| S-EPMC6866082 | biostudies-literature
Project description:First syntheses of a deuterium-labeled very long C34-containing polyunsaturated fatty acid, C34:5n5.d(2), and three other unlabeled very long chain C30-32-containing polyunsaturated fatty acids are reported here. These syntheses were achieved by coupling chemically modified C22- and C20-containing polyunsaturated fatty acids with carbanions derived from arylalkyl sulfones, followed by sodium amalgam-mediated desulfonylation.
| S-EPMC2976573 | biostudies-literature