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.

On the association between dietary oily fish intake and bone mineral density in frequent fish consumers of Amerindian ancestry. The three villages study.

Reports addressing the effects of oily fish intake on bone health are inconsistent. This study shows that consumption of ≥ 5.2 oily fish servings/week (728 g) is associated with lower prevalence of osteopenia/osteoporosis in elderly women of Amerindian ancestry. Results suggest a beneficial effect of oily fish intake in this population. OBJECTIVES: Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids and other nutrients that may have a positive effect on bone health. However, this association is inconsistent and seems to be more evident in certain ethnic groups. We aimed to assess the association between oily fish intake and bone mineral density (BMD) in frequent fish consumers of Amerindian ancestry living in rural Ecuador. METHODS: This study included 399 individuals aged ≥ 60 years living in three neighboring rural villages of coastal Ecuador. Dietary oily fish intake was quantified systematically using validated surveys and BMD was determined by dual-energy x-ray absorptiometry. Ordinal logistic regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the independent association between oily fish intake and bone health. RESULTS: Participants had a mean age of 68.8 ± 6.8 years, and 58% were women. The mean intake of oily fish was 8.5 ± 4.7 servings/week, with 308 (77%) reporting high fish intake (≥ 5.2 servings/week [728 g]). Ninety-four (24%) participants had normal BMD T-scores, 149 (37%) had osteopenia, and 156 (39%) had osteoporosis. Ordinal logistic regression models showed no association between high fish intake and bone health in the total population. When men and women were analyzed separately, the association became significant for women only in both unadjusted (OR: 2.52; 95% C.I.: 1.22 - 5.23) and fully-adjusted models (OR: 2.23; 95% C.I.: 1.03 - 4.81). CONCLUSION: Consumption of ≥ 5.2 oily fish servings/week is associated with lower prevalence of osteopenia and osteoporosis in elderly women of Amerindian ancestry.

Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.

Polyunsaturated ω3 fatty acids prevent the cardiac hypertrophy in hypertensive rats.

It has been demonstrated that supplementation with the two main omega 3 polyunsaturated fatty acids (ω3 FAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), leads to modifications in the cardiac physiology. ω3 FAs can affect the membrane's lipid composition, as well as proteins' location and/or function. The Na+/H+ exchanger (NHE1) is an integral membrane protein involved in the maintenance of intracellular pH and its hyperactivity has been associated with the development of various cardiovascular diseases such as cardiac hypertrophy. Our aim was to determine the effect of ω3 FAs on systolic blood pressure (SBP), lipid profiles, NHE1 activity, and cardiac function in spontaneously hypertensive rats (SHR) using Wistar rats (W) as normotensive control. After weaning, the rats received orally ω3 FAs (200 mg/kg body mass/day/ 4 months). We measured SBP, lipid profiles, and different echocardiography parameters, which were used to calculate cardiac hypertrophy index, systolic function, and ventricular geometry. The rats were sacrificed, and ventricular cardiomyocytes were obtained to measure NHE1 activity. While the treatment with ω3 FAs did not affect the SBP, lipid analysis of plasma revealed a significant decrease in omega-6/omega-3 ratio, correlated with a significant reduction in left ventricular mass index in SHR. The NHE1 activity was significantly higher in SHR compared with W. While in W the NHE1 activity was similar in both groups, a significant decrease in NHE1 activity was detected in SHRs supplemented with ω3 FAs, reaching values comparable with W. Altogether, these findings revealed that diet supplementation with ω3 FAs since early age prevents the development of cardiac hypertrophy in SHR, perhaps by decreasing NHE1 activity, without altering hemodynamic overload.

Linseed oil attenuates fatty liver disease in mice fed a high-carbohydrate diet

The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.2%), and lipids (4.0%). The Control HCD group (HCD-C) received an HCD containing lard (3.6%) and soybean oil (0.4%) as lipid sources. The L10 and L100 groups received an HCD with 10 and 100% linseed oil as lipid sources, respectively. A group of mice were euthanized before receiving the diets (day 0) and the remaining groups after 56 days of receiving the diets (HCD-C, L10, and L-100 groups). Morphological and histopathological analyses, as well as collagen deposition were evaluated. Perivenous hepatocytes (PVH) of the HCD-C group were larger (P<0.05) than periportal hepatocytes (PPH) in the median lobe (ML) and left lobe (LL). There was a greater (P<0.05) deposition of type I collagen in PPH (vs PVH) and in the ML (vs LL). The ML exhibited a higher proportion of apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning. All these alterations (hepatocyte size, deposition of type I collagen, apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning) induced by HCD were prevented or attenuated in L10 and L100 groups. Another indicator of the beneficial effects of linseed oil was the lower (P<0.05) number of binucleated hepatocytes (HCD-C vs L10 or L100 group). In general, the L100 group had greater effects than the L10 group. In conclusion, linseed oil impedes or reduces the liver injury progression induced by an HCD.

Linseed oil attenuates fatty liver disease in mice fed a high-carbohydrate diet

The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.2%), and lipids (4.0%). The Control HCD group (HCD-C) received an HCD containing lard (3.6%) and soybean oil (0.4%) as lipid sources. The L10 and L100 groups received an HCD with 10 and 100% linseed oil as lipid sources, respectively. A group of mice were euthanized before receiving the diets (day 0) and the remaining groups after 56 days of receiving the diets (HCD-C, L10, and L-100 groups). Morphological and histopathological analyses, as well as collagen deposition were evaluated. Perivenous hepatocytes (PVH) of the HCD-C group were larger (P<0.05) than periportal hepatocytes (PPH) in the median lobe (ML) and left lobe (LL). There was a greater (P<0.05) deposition of type I collagen in PPH (vs PVH) and in the ML (vs LL). The ML exhibited a higher proportion of apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning. All these alterations (hepatocyte size, deposition of type I collagen, apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning) induced by HCD were prevented or attenuated in L10 and L100 groups. Another indicator of the beneficial effects of linseed oil was the lower (P<0.05) number of binucleated hepatocytes (HCD-C vs L10 or L100 group). In general, the L100 group had greater effects than the L10 group. In conclusion, linseed oil impedes or reduces the liver injury progression induced by an HCD.

Fish oil and probiotics supplementation through milk chocolate improves spatial learning and memory in male Wistar rats.

Background: Cognition and brain function is critical through childhood and should be improved with balanced diets. Incorporating bioactive ingredients such as omega-3 polyunsaturated fatty acids (ω3 PUFAs) and probiotics into food formulations could be used as an approach to improve cognitive function. This study evaluated the effects on cognitive capacity of complementing rodent diets with chocolate, by itself and in combination with ω3 PUFAs from fish oil and probiotics. Methods: Spatial learning and memory in the rats were determined by the Barnes maze test in short- and long-term memory. Samples from the cecum were obtained to assess microbial counts (Lactobacillus, Bifidobacterium, Enterobacteriaceae, and total bacteria), and brains were recovered to analyze the neural morphology of the tissues. Also, glucose, brain weights, and epididymal tissue were analyzed. Results: The combination of chocolate with fish oil and probiotics improved the memory of rats compared to the result of each bioactive compound when evaluated separately. Treatments did not affect sugar level, epididymal adipose tissue, or brain weight. On the other hand, consuming probiotics alone or in combination with chocolate decreased Enterobacteria counts, while Lactobacillus and Bifidobacteria counts were not affected. Neural morphological analysis showed that combining chocolate with probiotics and ω3 PUFAs increased the number of neurons in the hippocampal CA1 and CA3 regions. Conclusion: Chocolate added with probiotics and ω3 PUFAs improved spatial memory and learning in the studied model.

Sous-vide-cooked ω3-enriched chicken hamburger: Physicochemical and sensory characterization

ABSTRACT We designed a chicken-meat hamburger enriched with ω3 polyunsaturated fatty acids and cooked by sous-vide. The chicken meat used came from male BB chickens of the Cobb commercial line, fed for approximately 27 days with 3 isoprotein and isoenergetic diets based on: corn and soy; soybeans plus flax oil and soybeans plus fish oil. The hamburgers, made with a mixture of fresh skinless chicken breast and thigh meat, oat bran and a commercial mix of spices, were vacuum-packed and cooked at 80 °C for 10 min. Chemical analyses (moisture, fat, protein, fiber, thiobarbituric acid and fatty acid profile), color and texture profile were performed. The samples enriched with fish oil presented significantly higher values of docosapentaenoic acid (1.53 g of fatty acid per 100 g of fat) than the control sample (0.30 g of fatty acid per 100 g of fat). The sensory characterization was carried out by 54 consumers using the CATA methodology (check all that apply). The chicken-meat hamburger enriched with fish-ω3 oil was the most widely accepted by consumers. Therefore, a functional food product enriched with ω3 polyunsaturated acid close to the daily recommendation (250 mg) was designed. The sensory acceptability of consumers was found based on a pleasant taste, pleasant appearance and chicken flavor.

RESUMEN Se diseñó una hamburguesa de carne de pollo enriquecida con ácidos grasos ω3 poliinsaturados y cocida al vacío. La carne de pollo provino de pollos BB machos de la línea comercial Cobb, alimentados durante aproximadamente 27 días con 3 dietas isoproteicas e isoenergéticas en base a: maíz y soja; soja más aceite de lino y soja más aceite de pescado. Las hamburguesas, elaboradas con una mezcla de carne fresca de pechuga y pata muslo de pollo sin piel, salvado de avena y mezcla comercial de especias, se envasaron y cocinaron al vacío a 80 °C durante 10 min. Se realizaron análisis químicos (humedad, grasa, proteína, fibra, ácido tiobarbitúrico y perfil de ácidos grasos), color y perfil de textura. Las muestras enriquecidas con aceite de pescado presentaron valores significativamente mayores de ácidos docosapentaenoico (1,53 g de ácido graso por 100 g de grasa) que la muestra control (0,30 g de ácido graso por 100 g de grasa). La caracterización sensorial fue realizada por 54 consumidores utilizando la metodología CATA (marque todo lo que corresponda). La hamburguesa de pollo y enriquecida con aceite de pescado ω3 fue la más aceptada por los consumidores. Por lo tanto, se diseñó un producto alimenticio funcional en forma de hamburguesa de pollo que se enriqueció con ω3 poliinsaturados cerca de la recomendación diaria (250 mg), y se consideró un producto aceptable por el consumidor sobre la base del sabor agradable, apariencia agradable y sabor a pollo.

Dietary oily fish intake and progression of diffuse subcortical damage of vascular origin: A longitudinal prospective study in community-dwelling older adults.

Introduction: Oily fish intake may reduce the progression of white matter hyperintensities (WMH) of presumed vascular origin due to their high content of omega-3 polyunsaturated fatty acids and other nutrients. However, information on this relationship is limited. We aimed to assess the association between oily fish intake and WMH progression in older adults living in rural coastal Ecuador. Methods: Participants of the Atahualpa Project Cohort received baseline clinical interviews and brain MRIs. Oily fish intake was calculated at every annual door-to-door survey from enrollment to the end of the study. Individuals who also received a follow-up brain MRI were included. Poisson regression models were fitted to assess the incidence rate ratio (IRR) of WMH progression according to the amount of oily fish intake, after adjusting for demographics, level of education and traditional vascular risk factors. Results: The study included 263 individuals of Amerindian ancestry aged ⩾60 years (mean age: 65.7 ± 6.2 years; 57% women). The mean oily fish intake was 8.3 ± 4 servings per week. Follow-up MRIs demonstrated WMH progression in 103 (39%) individuals after a median follow-up of 6.5 years. A multivariate Poisson regression model showed an inverse relationship between oily fish intake and WMH progression (IRR: 0.89; 95% CI: 0.84-0.95; p < 0.001). A similar model also revealed an inverse relationship between tertiles of oily fish intake and probabilities of WMH progression, which became significant when individuals allocated to the third tertile were compared to those in the first and second tertiles. Conclusion: Study results show an inverse relationship between the amount of oily fish intake and WMH progression in frequent fish consumers of Amerindian ancestry.

Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I.

Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1ß concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals' locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

Nitrogen Sources Affect the Long-Chain Polyunsaturated Fatty Acids Content in Thraustochytrium sp. RT2316-16.

The psychrophilic marine microorganism Thraustochytrium sp. RT2316-16 can produce carotenoids as well as lipids containing the omega-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid and docosahexaenoic acid. This work reports on the effects of the composition of the culture medium, including certain amino acids, on growth and lipid synthesis by RT2316-16. Compared with the culture on glutamate, the use of lysine, alanine, or serine, increased the content of the omega-3 PUFA in total lipids. In the media that contained yeast extract, glutamate, and glucose, lipid accumulation occurred when organic ammonium was exhausted earlier than glucose. In contrast, lipid mobilization was promoted if glucose was exhausted while organic ammonium (supplied by yeast extract and glutamate) remained in the medium. The total content of carotenoids in the lipid-free biomass decreased during the first 12 to 24 h of culture, simultaneously with a decrease in the total lipid content of the biomass. The experimental data suggested a possible interrelationship between the metabolism of carotenoids and lipids. A high content of omega-3 PUFA in the total lipids could be obtained by growing the thraustochytrid in a medium with a low glucose concentration (6 g L-1) and a high concentration of organic nitrogen (yeast extract 12 g L-1; glutamate 1.06 g L-1), after glucose was exhausted. These observations may guide the development of a strategy to enhance omega-3 PUFA in the biomass.

Chocolate as Carrier to Deliver Bioactive Ingredients: Current Advances and Future Perspectives.

Consumer demand for healthier foods with improved taste and convenience has urged the food industry to develop functional foods added with bioactive ingredients that can supplement basic nutrition (food supplement) or exert a pharmacological effect (nutraceuticals). Chocolate could be used as an ideal carrier to deliver bioactive ingredients, mainly due to its high acceptability by consumers. However, a drawback of using chocolate as functional food is its high sugar content, which impedes its commercialization with the diabetic population. Therefore, there is need to develop sugar-free chocolate formulations added with bioactive ingredients. Nevertheless, sugar replacement and bioactive ingredients addition is a major technological challenge that affects texture, rheology, and sensory properties of chocolate. This review is designed as a practical guide for researchers and food industries to develop the next generation of functional chocolates. Different functional chocolate formulations, including sugar-free, are reviewed as potential carriers for the delivery of bioactive compounds. The physicochemical properties and sensory acceptability of the functional chocolates presented are also highlighted. Finally, future perspectives, such as the use of nanotechnology to improve the bioaccessibility and bioavailability of active ingredients, as well as the need for clinical trials to validate the pharmacological effect of functional chocolates, are also discussed.

Moderating effect of PLIN4 genetic variant on impulsivity traits in 5-year-old-children born small for gestational age.

Poor fetal growth is associated with long-term behavioral, metabolic and psychiatric alterations, including impulsivity, insulin resistance, and mood disorders. However, the consumption of omega-3 polyunsaturated fatty acid (n-3 PUFA) seems to be protective for this population, improving inhibitory control and behavioral reactivity. We investigated whether the presence of the A allele of rs8887 SNP (PLIN4 gene), known to be associated with increased sensitivity to the consumption of n-3 PUFAs, interacts with fetal growth influencing inhibitory control. 152 five-year-old children were genotyped and performed the Stop Signal Task (SSRT). There was a significant interaction between birth weight and the presence of the A allele on SSRT performance, in which lower birth weight associated with poorer inhibitory control only in non-carriers. These results suggest that a higher responsiveness to n-3 PUFAS protects small for gestational age children from developing poor response inhibition, highlighting that optimizing n-3 PUFA intake may benefit this population.

Effects of intermittent dietary supplementation with conjugated linoleic acid and fish oil (EPA/DHA) on body metabolism and mitochondrial energetics in mice.

Understanding the mitochondrial processes that contribute to body energy metabolism may provide an attractive therapeutic target for obesity and co-morbidities. Here we investigated whether intermittent dietary supplementation with conjugated linoleic (CLA, 18:2n-6), docosahexaenoic (22:6n-3, DHA) and eicosapentaenoic (20:5n-3, EPA) acids, either alone or in combination, changes body metabolism associated with mitochondrial functions in the brain, liver, skeletal muscle and brown adipose tissue (BAT). Male C57Bl/6 mice were divided into groups: CLA (50% cis-9, trans-11; 50% trans-10, cis-12), EPA/DHA (64% EPA; 28% DHA), CLA plus EPA/DHA or control (linoleic acid). Each mouse received 3 g/kg b.w. of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA or EPA/DHA increased body VO2 consumption, VCO2 production and energy expenditure, being fish oil (FO) the most potent even in combination with CLA. Individually, both oils reduced mitochondrial density in BAT. CLA supplementation alone also a) elevated the expression of uncoupling proteins in soleus, liver and hippocampus and the uncoupling activity in the last two, ad this effect was associated with reduced hydrogen peroxide production in hippocampus; b) increased proteins related to mitochondrial fission in liver. EPA/DHA supplementation alone also a) induced mitochondrial biogenesis in liver, soleus and hippocampus associated with increased expression of PGC1-α; b) induced proteins related to mitochondrial fusion in the liver, and fission and fusion in the hippocampus. Therefore, this study shows changes on mitochondrial mechanisms induced by CLA and/or EPA/DHA that can be associated with elevated body energy expenditure.

Fish oil prevents rodent anxious states comorbid with diabetes: A putative involvement of nitric oxide modulation.

There is an urgent need to understand the pathophysiological mechanisms related to anxiety associated with diabetes, seeking more effective alternative treatments to treat it. For that, the effect of a preventive and prolonged treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, was tested in streptozotocin-diabetic (DBT) rats submitted to the anxiety tests. Additionally, an immunohistochemistry for neuronal NO synthase (nNOS) was performed in brain areas related to anxiety, such as lateral amygdala (AMY), hippocampus (HIP) and dorsolateral periaqueductal gray (dlPAG). Lastly, the effect of NO precursor L-arginine (L-Arg) or nNOS inhibitor 7-nitroindazole (7-NI) was tested in DBT animals treated with vehicle (VEH) or FO. Our data demonstrated that vehicle-treated DBT animals exhibited a more pronounced anxiogenic-like response and also presented high nNOS levels in the AMY, HIP and rostral dlPAG, what were both significantly prevented by FO treatment. This treatment was able to prevent the impairment in locomotor activity besides improving the high glycemic levels in DBT rats. Interestingly, while injection of 7-NI or L-Arg in VEH-treated DBT animals induced an anxiogenic-like and anxiolytic-like effect, respectively; the previous treatment with both L-Arg and 7-NI in FO-DBT animals abolished the anxiolytic-like effect induced by FO treatment. Altogether, our data support the hypothesis that a dysregulation in the NO production in brain areas as AMY, HIP and dlPAG may contribute to the mechanisms that link anxiety and diabetes, and the prevention of nNOS brain expression changes induced by a prolonged treatment with FO may be an important mechanism related to its anxiolytic-like effect.

Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPARγ-dependent and PPARγ-independent actions.

SCOPE: We tested herein the hypothesis that peroxisome proliferator activated receptor γ (PPARγ) is a major mediator of omega-3 (n-3) protective actions against high-fat diet (HFD) induced obesity, glucose intolerance, and adipose tissue inflammation. METHODS AND RESULTS: C57BL6 wild-type and fat-1 transgenic (fat-1) mice were fed a low-fat diet (LFD) or HFD, treated or not with PPARγ antagonist, and evaluated for energy balance, adiposity, glucose tolerance, and adipose tissue inflammation. Fat-1 mice were protected from obesity, fasting hyperglycemia, glucose intolerance, and adipose tissue inflammation. PPARγ inhibition completely abolished fat-1 protection against HFD-induced glucose intolerance, but not obesity or adipose tissue inflammation. To investigate the role of myeloid cell as mediator of n-3 beneficial metabolic actions, mice with deletion (LyzM-PPARγ(KO)) or nondeletion (LyzM-PPARγ(WT)) of PPARγ in myeloid cells were fed either LFD or HFD (lard) or an HFD rich in n-3 (fish oil). Our findings indicate that myeloid cell associated PPARγ is not involved in the attenuation of HFD-induced glucose intolerance and adipose tissue inflammation induced by n-3. CONCLUSION: High endogenous n-3 fatty acid levels protect from HFD obesity, glucose intolerance, and adipose tissue inflammation. Among these, only protection against glucose intolerance is mediated by non-myeloid cell PPARγ.

Fibrates and fish oil, but not corn oil, up-regulate the expression of the cholesteryl ester transfer protein (CETP) gene.

Cholesteryl ester transfer protein (CETP) is a plasma protein that reduces high density lipoprotein (HDL)-cholesterol (chol) levels and may increase atherosclerosis risk. n-3 and n-6 polyunsaturated fatty acids (PUFAs) are natural ligands, and fibrates are synthetic ligands for peroxisome proliferator activated receptor-alpha (PPARα), a transcription factor that modulates lipid metabolism. In this study, we investigated the effects of PUFA oils and fibrates on CETP expression. Hypertriglyceridemic CETP transgenic mice were treated with gemfibrozil, fenofibrate, bezafibrate or vehicle (control), and normolipidemic CETP transgenic mice were treated with fenofibrate or with fish oil (FO; n-3 PUFA rich), corn oil (CO, n-6 PUFA rich) or saline. Compared with the control treatment, only fenofibrate significantly diminished triglyceridemia (50%), whereas all fibrates decreased the HDL-chol level. Elevation of the CETP liver mRNA levels and plasma activity was observed in the fenofibrate (53%) and gemfibrozil (75%) groups. Compared with saline, FO reduced the plasma levels of nonesterified fatty acid (26%), total chol (15%) and HDL-chol (20%). Neither of the oil treatments affected the plasma triglyceride levels. Compared with saline, FO increased the plasma adiponectin level and reduced plasma leptin levels, whereas CO increased the leptin levels. FO, but not CO, significantly increased the plasma CETP mass (90%) and activity (23%) as well as increased the liver level of CETP mRNA (28%). In conclusion, fibrates and FO, but not CO, up-regulated CETP expression at both the mRNA and protein levels. We propose that these effects are mediated by the activation of PPARα, which acts on a putative PPAR response element in the CETP gene.

Efeitos dos ácidos graxos ômega-3 em mulheres com câncer de mama: uma revisão da literatura / Effects of omega-3 fatty acids in women with breast cancer: a review of the literature

O objetivo da pesquisa foi investigar, na literatura, os efeitos dos ácidos graxos ômega-3 (AGs w-3) na prevenção e no tratamento do câncer de mama feminino. Métodos: Trata-se de uma revisão da literatura, utilizando-se artigos indexados nas bases de dados Medline, Lilacs, Scielo e Google scholar, com ênfase nos últimos cinco anos, nos idiomas português, inglês e espanhol. Foram selecionados estudos experimentais, clínicos randomizados, observacionais, epidemiológicos, entre outros, seguidos de tratamento estatístico com significância de p < 0.05. Resultados: Estudos demonstram que o consumo regular de AGs w-3 é capaz de reduzir a incidência de tumores mamários femininos induzidos experimentalmente. Em humanos e em animais de laboratório, pesquisas têm vinculado o alto consumo de peixes (ou óleo de peixe) na redução do risco de desenvolvimento do câncer de mama feminino e sugerem que a ingestão mais apropriada está na proporção de 2:1 (de ômega-6 para ômega-3). Ensaios clínicos com intervenções dietéticas com o objetivo de prevenir ou tratar o câncer devem ser cuidadosamente projetados para superar essas limitações e proporcionar uma ótima relação de ácidos graxos ômega-6 para ômega-3. Conclusão: Os estudos sobre a prevenção do câncer de mama e os mecanismos de ação dos AGs w-3 ainda são inconclusivos, porém, a maioria das evidências científicas demonstrou que a suplementação ou ingestão de w-3 está associada a menores incidências de tumores malignos mamários. Entretanto, mais estudos controlados e randomizados são necessários para elucidar os reais efeitos dos AGs w-3 na carcinogênese mamária, a dosagem adequada e o seu mecanismo de ação.

The objective of the research was to investigate, in literature, the effects of omega-3 fatty acids (w-3 FAs) in the prevention and treatment of female breast cancer. Methods: This is a review of the literature, using indexed articles in Medline, Lilacs, SciELO and Google scholar database, with emphasis in the last five years, in Portuguese, English and Spanish languages. We selected experimental studies, clinical trials, observational, epidemiological, among others, followed by treatment with a statistical significance of p < 0.05. Results: Studies show that regular consumption of w-3 FAs is able to reducethe incidence in experimentally induced female breast tumors. In humans and laboratory animals, research has linked the high consumption of fish (or fish oil) to the reduction of the risk in developing female breast cancer and it is suggested that the more appropriate intake ratiois of 2:1 (omega-6 to omega-3). Clinical trials with dietary interventions aimed at preventing or treating cancer should be carefully designed to overcome these limitations and provide an optimal ratio percentage of omega-6 to omega-3. Conclusion: The studies on breast cancer prevention and the w-3 FAs mechanisms of action are still inconclusive, but most of the scientific evidence has shown that supplement or intake of w-3 is associated to lower incidences of malignant breast tumors. However, more randomized controlled trials are needed to elucidate the actual effects of w-3 FAs in breast carcinogenesis, the proper dosage and its mechanism of action.