The polyunsaturated fatty acid docosahexaenoic affects mitochondrial function in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) shows a rewired metabolism featuring increased fatty acid uptake and synthesis via de novo lipogenesis, both sharply related to mitochondrial physiology. The docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that exerts its antitumoral properties via different mechanisms, but its specific action on mitochondria in PCa is not clear. Therefore, we investigated whether the DHA modulates mitochondrial function in PCa cell lines. METHODS: Here, we evaluated mitochondrial function of non-malignant PNT1A and the castration-resistant (CRPC) prostate 22Rv1 and PC3 cell lines in response to DHA incubation. For this purpose, we used Seahorse extracellular flux assay to assess mitochondria function, [14C]-glucose to evaluate its oxidation as well as its contribution to fatty acid synthesis, 1H-NMR for metabolite profile determination, MitoSOX for superoxide anion production, JC-1 for mitochondrial membrane polarization, mass spectrometry for determination of phosphatidylglycerol levels and composition, staining with MitoTracker dye to assess mitochondrial morphology under super-resolution in addition to Transmission Electron Microscopy, In-Cell ELISA for COX-I and SDH-A protein expression and flow cytometry (Annexin V and 7-AAD) for cell death estimation. RESULTS: In all cell lines DHA decreased basal respiratory activity, ATP production, and the spare capacity in mitochondria. Also, the omega-3 induced mitochondrial hyperpolarization, ROS overproduction and changes in membrane phosphatidylglycerol composition. In PNT1A, DHA led to mitochondrial fragmentation and it increased glycolysis while in cancer cells it stimulated glucose oxidation, but decreased de novo lipogenesis specifically in 22Rv1, indicating a metabolic shift. In all cell lines, DHA modulated several metabolites related to energy metabolism and it was incorporated in phosphatidylglycerol, a precursor of cardiolipin, increasing the unsaturation index in the mitochondrial membrane. Accordingly, DHA triggered cell death mainly in PNT1A and 22Rv1. CONCLUSION: In conclusion, mitochondrial metabolism is significantly affected by the PUFA supplementation to the point that cells are not able to proliferate or survive under DHA-enriched condition. Moreover, combination of DHA supplementation with inhibition of metabolism-related pathways, such as de novo lipogenesis, may be synergistic in castration-resistant prostate cancer.

Genome-scale metabolic modeling of Thraustochytrium sp. RT2316-16: Effects of nutrients on metabolism.

Marine thraustochytrids produce metabolically important lipids such as the long-chain omega-3 polyunsaturated fatty acids, carotenoids, and sterols. The growth and lipid production in thraustochytrids depends on the composition of the culture medium that often contains yeast extract as a source of amino acids. This work discusses the effects of individual amino acids provided in the culture medium as the only source of nitrogen, on the production of biomass and lipids by the thraustochytrid Thraustochytrium sp. RT2316-16. A reconstructed metabolic network based on the annotated genome of RT2316-16 in combination with flux balance analysis was used to explain the observed growth and consumption of the nutrients. The culture kinetic parameters estimated from the experimental data were used to constrain the flux via the nutrient consumption rates and the specific growth rate of the triacylglycerol-free biomass in the genome-scale metabolic model (GEM) to predict the specific rate of ATP production for cell maintenance. A relationship was identified between the specific rate of ATP production for maintenance and the specific rate of glucose consumption. The GEM and the derived relationship for the production of ATP for maintenance were used in linear optimization problems, to successfully predict the specific growth rate of RT2316-16 in different experimental conditions.

Effect of fish-oil supplementation on the glycemic and lipidemic profiles of pregnant women: a systematic review and meta-analysis.

CONTEXT: Pregnant women have physiological metabolic changes in glycemic and lipid profiles that are essential for fetal development. OBJECTIVE: The aim of this systematic review was to analyze the effects of fish-oil-capsule supplementation on the glycemic and lipid profiles of pregnant women. DATA SOURCES: A systematic search was conducted of the MEDLINE (by PubMed), Embase, Cochrane Library (CENTRAL) databases and gray literature, including preprints for all relevant studies published in English, with no date restrictions. DATA EXTRACTION: The estimated pooled results were analyzed using a random-effects model and represented by mean differences (MDs) and corresponding 95% confidence intervals (CIs). The analyses were performed with R software, version 4.2.1, using the "Meta" packages, versions 6.0-0. DATA ANALYSIS: Fifteen eligible studies were included after screening. In a pooled analysis, overall fish-oil supplementation had no effect on parameters compared with placebo. In the subgroup analysis, fish-oil supplementation may be beneficial in insulin (MD: -2.11 IU/mL; 95% CI: -3.86, -0.36) and homeostasis model assessment of insulin resistance (HOMA-IR) (MD: -0.71; 95% CI: -1.14, -0.29) indices, with heterogeneity (I2 =0%) among pregnant women with diabetes mellitus. In the subgroup with doses of eicosapentaenoic acid (EPA) below 200 mg, there was a reduction in HOMA-IR in the intervention group (MD: -0.60; 95% CI: -1.14, -0.06). CONCLUSION: Pregnant women taking fish-oil capsules showed significant beneficial changes in the subgroups of type 2 diabetes and EPA dosages below 200 mg for insulin and HOMA-IR.

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

OBJECTIVE: Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. METHODS: This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. RESULTS: A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. CONCLUSIONS: Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice.

A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4-6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.

Coenzyme Q in Thraustochytrium sp. RT2316-16: Effect of the Medium Composition.

Coenzyme Q (CoQ; ubiquinone) is an essential component of the respiratory chain. It is also a potent antioxidant that prevents oxidative damage to DNA, biological membranes, and lipoproteins. CoQ comprises a six-carbon ring with polar substituents that interact with electron acceptors and donors, and a hydrophobic polyisoprenoid chain that allows for its localization in cellular membranes. Human CoQ has 10 isoprenoid units (CoQ10) within the polyisoprenoid chain. Few microorganisms produce CoQ10. This work shows that Thraustochytrium sp. RT2316-16 produces CoQ10 and CoQ9. The CoQ10 content in RT2316-16 depended strongly on the composition of the growth medium and the age of the culture, whereas the CoQ9 content was less variable probably because it served a different function in the cell. Adding p-hydroxybenzoic acid to the culture media positively influenced the CoQ10 content of the cell. The absence of some B vitamins and p-aminobenzoic acid in the culture medium negatively affected the growth of RT2316-16, but reduced the decline in CoQ10 that otherwise occurred during growth. The highest content of CoQ9 and CoQ10 in the biomass were 855 µg g-1 and 10 mg g-1, respectively. The results presented here suggest that the thraustochytrid RT2316-16 can be a potential vehicle for producing CoQ10. Metabolic signals that trigger the synthesis of CoQ10 in RT2316-16 need to be determined for optimizing culture conditions.

The Supplementation of Docosahexaenoic Acid-Concentrated Fish Oil Enhances Cognitive Function in Puppies.

Docosahexaenoic acid (DHA) has an important role in brain development and functionality. Therefore, this study aimed to evaluate the effects of DHA-concentrated fish oil on the cognitive function of puppies. Twelve 3-month-old puppies were included, blocked by breed and randomly distributed into two groups: the Control Group (CG), without supplementation, and the Experimental Group (EG), supplemented with 40 mg DHA/kg BW/day. The object discrimination test was used, with a normal stage (NS) and a reverse stage (RS), and blood samples were collected to evaluate the serum polyunsaturated fatty acid (PUFA) concentration and total antioxidant capacity (TAC) before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after beginning the study. For the NS, there were effects of treatment (p = 0.0039) and time (p < 0.0001), in which the correct answer frequency in the EG was higher than the CG. The serum eicosapentaenoic acid (EPA) + HA concentrations at T1, T2 and T3 were higher than at T0 for the EG (p = 0.0159), in addition, EG showed higher serum EPA + DHA concentrations than CG at T2 (p = 0.0245). The TAC values were similar between the groups (p = 0.3211). It was concluded that the cognitive function of puppies can be enhanced with DHA-concentrated fish oil supplementation without increasing the serum lipid oxidation.

Lipid profile and cost of enteral nutrition formula with addition of fish oil used in a public hospital.

BACKGROUND & AIMS: The present study evaluated the lipid profile of enteral nutrition formulas with added fish oil used in a public hospital, with an emphasis on the fatty acid (FA) composition. METHODS: FA composition was determined using gas chromatography coupled to a flame ionization detector (GC-FID). Nine enteral nutrition formulas were evaluated and the results obtained were compared with those reported on the formulas labels. RESULTS: The sample with the highest percentage of added fish oil according to the label information had the lowest total amounts of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) (p < 0.05). In the evaluation of the total amount of polyunsaturated fatty acids/saturated fatty acids (ΣPUFA/ΣSFA) ratio, five samples were not within the values recommended by Brazilan and international health regulatory agencies. Regarding the n-6/n-3 fatty acids ratio, five samples showed values higher than the recommended ratio. It was observed that EPA + DHA content was positively correlated with the cost of the diet. Importantly, we also found that there was a significant difference between the results of our analysis and the descriptions found on the labels for fatty acids n-6, n-3, EPA, DHA, SFA, PUFA and MUFA. CONCLUSIONS: We conclude that the discrepancies for fatty acids between the values obtained in the analyses and the values reported on the labels highlight the need for more rigorous inspection when public hospitals purchase enteral nutrition formulas with added fish oil, since the administration of formulas with inadequate levels of FA in hospitalized patients can compromise clinical results during the hospitalization period.

Potential Clinical Applications of Pro-Resolving Lipids Mediators from Docosahexaenoic Acid.

Docosahexaenoic acid (C22:6n-3, DHA) is the precursor of specialized pro-resolving lipid mediators (SPMs), such as resolvin, protectin, and maresin families which have been considered therapeutic bioactive compounds for human health. Growing evidence indicates that DHA and SPMs are beneficial strategies in the amelioration, regulation, and duration of inflammatory processes through different biological actions. The present review discusses the reported therapeutic benefits of SPMs on various diseases and their potential clinical applications.

The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments.

In order to understand how omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles published in the last 5 years in two databases was performed. Of the 679 articles identified, only 27 were included and examined based on five topics, taking into account: the induction type of the breast cancer used in animal models; the characteristics of the induction model by cell transplantation; the experimental design of the ω-3 supplementation-combined or not with a treatment antitumor drug; the fatty acids (FAs) composition used; the analysis of the studies' outcomes. There are diverse and well-established animal models of breast cancer in the literature, with very relevant histological and molecular similarities depending on the specific objective of the study, such as whether the method of tumor induction was transgenic, by cell transplantation, or by oncogenic drugs. The analyses of outcomes were mainly focused on monitoring tumor growth, body/tumor weight, and molecular, genetic, or histological analyses, and few studies evaluated latency, survival, or metastases. The best results occurred when supplementation with ω-3 PUFA was associated with antitumor drugs, especially in the analysis of metastases and volume/weight of tumors or when the supplementation was started early and maintained for a long time. However, the beneficial effect of ω-3 PUFA supplementation when not associated with an antitumor agent remains unclear.

Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity.

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis.

Background: Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. Aim: We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. Methodology: A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. Results: In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. Conclusion: The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.

AMP kinase activation by Omega-3 polyunsaturated fatty acid protects the retina against ischemic insult: An in vitro and in vivo study.

PURPOSE: To investigate the possible beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) in ischemic retinal angiogenesis and whether AMP-activated protein kinase (AMPK) is involved. METHODS: Human retinal microvascular endothelial cells (hRMECs) were exposed to dimethyloxalylglycine (DMOG), a hypoxia-inducible factor hydroxylase inhibitor, in the presence or absence of docosahexaenoic acid (DHA) and small interfering RNA (siRNA) for AMPKα for 24 h. Ischemic factors, endothelial mesenchymal transition marker, endothelial barrier integrity, cell migration, and tube formation were evaluated. Neonatal AMPKα2-/- and control wild-type (WT) mice were submitted to an oxygen-induced retinopathy (OIR) protocol; their nursing mother mice were either fed ω3-PUFAs or not. In the end, ischemic markers and endothelial cell proliferation were evaluated in neonatal mouse retinal tissue through immunohistochemical or immunofluorescent assays among all studied groups. RESULTS: Cells exposed to DMOG displayed increased expressions of hypoxic and endothelial mesenchymal transition (vimentin) markers and barrier disarrangement of Zonula Occludens-1 compared to the control, accompanied by increased cellular migration and tube formation (p < 0.05). AMPK activity was significantly decreased. Supplementation with DHA restored the mentioned alterations compared to DMOG (p<0.05). In siRNAAMPKα-treated cells, the beneficial effects observed with DHA were abolished. DHA upregulated G-protein receptor-120 (GPR120), which promptly increased intracellular levels of calcium (p ≤ 0.001), which consequently increased Calcium/calmodulin-dependent protein kinase kinase ß expression (CaMKKß) thus phosphorylating AMPKThr172. AMPKα2-/- and wild-type (WT) OIR mice exhibited similar retinal ischemic changes, and the oral supplementation with ω3-PUFA efficiently prevented the noticed ischemic alterations only in WT mice, suggesting that AMPKα2 is pivotal in the protective effects of ω3-PUFA. CONCLUSIONS: ω3-PUFAs protect the retina from the effects of ischemic conditions, and this effect occurs via the GPR120-CaMKKß-AMPK axis. A better understanding of this mechanism might improve the control of pathological angiogenesis in retinal ischemic diseases.

Fatty acid profile of slow-growing broilers supplemented with biocomplexed minerals / Perfil de ácidos graxos de frangos de corte de crescimento lento suplementados com minerais biocomplexados

ABSTRACT: This study was conducted to evaluate the effects of dietary supplementation with biocomplexed selenium and chromium on the fatty acid profile of the breast and thigh of males and females broilers of the Label Rouge lineage. The experimental design was completely randomized arranged in a 3 x 2 factorial scheme corresponding to three diets (control; 0.40 ppm of chromium; 0.50 ppm of selenium) and two sexes. Each treatment consisted of three plots of five broilers. The fatty acid profile was evaluated in the breast and thigh samples. The addition of biocomplexed selenium in the broilers diets increased the content of long chain fatty acid of the omega 3 and 6 series (docosahexaenoic - DHA and arachidonic acids, respectively), the total of omega 6 and the stearic acid content on the breast (pectoralis major muscle). In addition, selenium supplementation caused a reduction in oleic acid content and in total of monounsaturated in the same muscle. Males had higher contents of linoleic and linolenic acids, and total of polyunsaturated; and lower content of oleic acid, total of monounsaturated and saturated in the thigh. The broilers supplemented with biocomplexed selenium and males presented better lipid quality in the muscle by breast and thigh, respectively.

RESUMO: Este estudo foi conduzido com o objetivo de avaliar os efeitos da suplementação dietética com selênio e cromo biocomplexados sobre o perfil de ácidos graxos do peito e da coxa de frangos de corte machos e fêmeas da linhagem Label Rouge. O delineamento experimental foi inteiramente casualizado em esquema fatorial 3 x 2 correspondendo a três dietas (controle; 0,40 ppm de cromo; 0,50 ppm de selênio) e dois sexos. Cada tratamento foi composto por três parcelas de cinco frangos de corte. O perfil de ácidos graxos foi avaliado nas amostras de peito e coxa. A adição de selênio biocomplexado na dieta de frangos de corte aumentou o teor de ácidos graxos de cadeia longa das séries ômega 3 e 6 (ácido docosahexaenóico - DHA e araquidônico, respectivamente), o total de ômega 6 e o conteúdo de ácido esteárico no peito (músculo pectoralis major). Além disso, a suplementação com selênio causou redução no teor de ácido oleico e no total de monoinsaturados no mesmo músculo. Os machos apresentaram maiores teores dos ácidos linoléico e linolênico e total de poliinsaturados; e menor conteúdo de ácido oleico, total de monoinsaturados e saturados na coxa. Os frangos suplementados com selênio biocomplexado e os machos apresentaram melhor qualidade lipídica no músculo do peito e coxa, respectivamente.

Fatty acid profile of slow-growing broilers supplemented with biocomplexed minerals / Perfil de ácidos graxos de frangos de corte de crescimento lento suplementados com minerais biocomplexados

This study was conducted to evaluate the effects of dietary supplementation with biocomplexed selenium and chromium on the fatty acid profile of the breast and thigh of males and females broilers of the Label Rouge lineage. The experimental design was completely randomized arranged in a 3 x 2 factorial scheme corresponding to three diets (control; 0.40 ppm of chromium; 0.50 ppm of selenium) and two sexes. Each treatment consisted of three plots of five broilers. The fatty acid profile was evaluated in the breast and thigh samples. The addition of biocomplexed selenium in the broilers diets increased the content of long chain fatty acid of the omega 3 and 6 series (docosahexaenoic - DHA and arachidonic acids, respectively), the total of omega 6 and the stearic acid content on the breast (pectoralis major muscle). In addition, selenium supplementation caused a reduction in oleic acid content and in total of monounsaturated in the same muscle. Males had higher contents of linoleic and linolenic acids, and total of polyunsaturated; and lower content of oleic acid, total of monounsaturated and saturated in the thigh. The broilers supplemented with biocomplexed selenium and males presented better lipid quality in the muscle by breast and thigh, respectively.

Este estudo foi conduzido com o objetivo de avaliar os efeitos da suplementação dietética com selênio e cromo biocomplexados sobre o perfil de ácidos graxos do peito e da coxa de frangos de corte machos e fêmeas da linhagem Label Rouge. O delineamento experimental foi inteiramente casualizado em esquema fatorial 3 x 2 correspondendo a três dietas (controle; 0,40 ppm de cromo; 0,50 ppm de selênio) e dois sexos. Cada tratamento foi composto por três parcelas de cinco frangos de corte. O perfil de ácidos graxos foi avaliado nas amostras de peito e coxa. A adição de selênio biocomplexado na dieta de frangos de corte aumentou o teor de ácidos graxos de cadeia longa das séries ômega 3 e 6 (ácido docosahexaenóico - DHA e araquidônico, respectivamente), o total de ômega 6 e o conteúdo de ácido esteárico no peito (músculo pectoralis major). Além disso, a suplementação com selênio causou redução no teor de ácido oleico e no total de monoinsaturados no mesmo músculo. Os machos apresentaram maiores teores dos ácidos linoléico e linolênico e total de poliinsaturados; e menor conteúdo de ácido oleico, total de monoinsaturados e saturados na coxa. Os frangos suplementados com selênio biocomplexado e os machos apresentaram melhor qualidade lipídica no músculo do peito e coxa, respectivamente.

Differential effects of omega-3 PUFAS on tumor progression at early and advanced stages in TRAMP mice.

BACKGROUND: In vitro studies evidenced antitumor effects of omega-3 polyunsaturated fatty acids ([n-3] PUFAs), but their effects on prostate cancer (PCa) remain controversial in epidemiological studies. Here we investigated whether an (n-3) PUFA-enriched diet affects tumor progression in transgenic adenocarcinoma of the mouse prostate (TRAMP), at early (12 weeks age) and advanced stages (20 weeks age). METHODS: TRAMP mice were fed with standard rodent diet (C12, C20) or (n-3) PUFA-enriched diet containing 10% fish oil (T12, T20). A group of 8 weeks age animals fed standard diet was also used for comparison (C8). The ventral prostate was processed for histopathological and immunohistochemical analyses and serum samples submitted to biochemical assays. RESULTS: At early stages, (n-3) PUFA increased the frequency of normal epithelium (3.8-fold) and decreased the frequency of high-grade intraepithelial neoplasia (3.3-fold) and in situ carcinoma (1.9-fold) in the gland, maintaining prostate pathological status similar to C8 group. At advanced stages, 50% of the animals developed a large primary tumor in both C20 and T20, and tumor weight did not differ (C20: 2.2 ± 2.4; T20: 2.8 ± 2.9 g). The ventral prostate of T12 and of T20 animals that did not develop primary tumors showed lower cell proliferation, tissue expressions of androgen (AR) and glucocorticoid (GR) receptors, than their respective controls. For these animals, (n-3) PUFA also avoided an increase in the number of T-lymphocytes, collagen fibers, and αSMA immunoreactivity, and preserved stromal gland microenvironment. (n-3) PUFA also lowered serum triglycerides and cholesterol, regulating the lipid metabolism of TRAMP mice. CONCLUSIONS: (n-3) PUFAs had a protective effect at early stages of PCa, delaying tumor progression in TRAMP mice, in parallel with reductions in cell proliferation, AR, and GR and maintenance of the stromal compartment of the gland. However, (n-3) PUFAs did not prevent the development of primary tumors for the T20 group, reinforcing the need for further investigation at advanced stages of disease.

Production of Carotenoids and Phospholipids by Thraustochytrium sp. in Batch and Repeated-Batch Culture.

The carotenogenic thraustochytrid Thraustochytrium sp. RT2316-16 was grown in batch and repeated-batch cultures using different feeds containing glucose, or glycerol, and yeast extract, for the production of lipids, phospholipids and carotenoids. RT2316-16 produced canthaxanthin, astaxanthin and ß-carotene. The effects of biotin, ascorbic acid, light and temperature were evaluated in some of the experiments. In 2-day-old batch cultures, the combined mass percentage of eicosapentaenoic acid and docosahexaenoic acid in total lipids was between 16.5% (glycerol-based medium in the dark; biomass concentration = 4.2 ± 1.1 g L-1) and 42.6% (glucose-based medium under light; biomass concentration = 3.3 ± 0.1 g L-1), decreasing to 3.8% and 6.1%, respectively, after day 4. In repeated-batch cultures, the total lipids in the biomass increased after glucose or glycerol was fed alone, whereas the total carotenoids (168 ± 7 µg g-1 dry weight (DW)) and phospholipids in the biomass increased after feeding with yeast extract. The biomass with the highest content of phospholipids (28.7 ± 4.3 mg g-1 DW) was obtained using a feed medium formulated with glycerol, yeast extract and ascorbic acid. Glycerol was the best carbon source for the production of a biomass enriched with total lipids (467 ± 45 mg g-1 DW). The composition of carotenoids depended strongly on the composition of the feed. Repeated-batch cultures fed with yeast extract contained canthaxanthin as the main carotenoid, whereas in the cultures fed only with glucose, the biomass contained mainly ß-carotene.

Pilot study of the effect of EPA + DHA supplementation on the fatty acid profile of erythrocytes and breast milk of lactating women from Sonsón, Colombia.

Objective: The objective of this study was to evaluate changes in the concentrations of EPA and DHA in the erythrocytes and breast milk of a group of lactating women in the municipality of Sonsón (Antioquia) before and after receiving supplementation with these fatty acids for three months. Design: In a quasi-experimental study, 11 lactating women were evaluated before and after EPA (100 mg) and DHA (250 mg) supplementation for three months. The consumption of omega-3 food sources was determined by simple frequency, anthropometry (weight, height) was performed, and the fatty acid profiles of erythrocytes and breast milk were determined with gas chromatography. Environment: Sonsón, Colombia. Participants: A group of lactating women in the municipality of Sonsón (Antioquia). Results: Low consumption of foods that are sources of omega-3 fatty acids was found, as was low EPA and DHA content in erythrocytes and breast milk at the beginning of the study period. After supplementation, there was no significant change for EPA, however, there was a significant increase in DHA in both erythrocytes and breast milk; in addition, there was a decrease in the omega-6/omega-3 ratio. Conclusions: Supplementation with 250 mg of DHA increased its concentration in the blood and breast milk to levels approaching the recommended average DHA of 0.3%, where benefits have been seen for the mother.

Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights.

Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.

Omega-3 Fatty Acids and Balanced Gut Microbiota on Chronic Inflammatory Diseases: A Close Look at Ulcerative Colitis and Rheumatoid Arthritis Pathogenesis.

The aim of this article was to review experimental and clinical studies regarding the use of omega-3 fatty acids on the prevention and control of chronic inflammatory diseases with autoimmune background through the gut microbiota modulation. For this, natural omega-3 sources are presented emphasizing the importance of a healthy diet for the body's homeostasis and the enzymatic processes that these fatty acids go through once inside the body. The pathogenesis of ulcerative colitis and rheumatoid arthritis are revisited under the light of the gut microbiota dysbiosis approach and how those fatty acids are able to prevent and control these two pathological conditions that are responsible for the global chronic burden and functional disability and life-threatening comorbidities if not treated properly. As a matter of reflection, as we are living a pandemic crisis owing to COVID-19 infection, we present the potential of omega-3 in preventing a poor prognosis once they contribute to balancing the immune system modulation the inflammatory process.