Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids.

Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss. Fish oil is a natural agonist for PPARγ and thus may exert its actions through the PPARγ pathway. We examined the role of PPARγ in body composition changes induced by a fish or safflower oil diet using two strains of C57BL/6J (B6); i.e. B6.C3H-6T (6T) congenic mice created by backcrossing a small locus on Chr 6 from C3H carrying 'gain of function' polymorphisms in the Pparγ gene onto a B6 background, and C57BL/6J mice. After 9months of feeding both diets to female mice, body weight, percent fat and leptin levels were less in mice fed the fish oil vs those fed safflower oil, independent of genotype. At the skeletal level, fish oil preserved vertebral bone mineral density (BMD) and microstructure in B6 but not in 6T mice. Moreover, fish oil consumption was associated with an increase in bone marrow adiposity and a decrease in BMD, cortical thickness, ultimate force and plastic energy in femur of the 6T but not the B6 mice. These effects paralleled an increase in adipogenic inflammatory and resorption markers in 6T but not B6. Thus, compared to safflower oil, fish oil (high ratio omega-3/-6) prevents weight gain, bone loss, and changes in trabecular microarchitecture in the spine with age. These beneficial effects are absent in mice with polymorphisms in the Pparγ gene (6T), supporting the tenet that the actions of n-3 fatty acids on bone microstructure are likely to be genotype dependent. Thus caution must be used in interpreting dietary intervention trials with skeletal endpoints in mice and in humans.

Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults.

The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05–2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28–4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18–3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92–2.94) and insulin resistance (OR 3.40–3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.

Quality of polyunsaturated fatty acids in Nile tilapias (Oreochromis niloticus) fed with vitamin E supplementation

Freshwater fish are an important source of protein, but they also contain other highly nutritive components such as fats. Polyunsaturated fatty acids (PUFAs) are essential for normal growth, development and reproduction of vertebrates. The antioxidant role of vitamin E in cell membranes prevents fatty acid and cholesterol oxidation, thereby promoting PUFA and subcellular particle stabilization. The effects of vitamin E supplementation on the quality of Nile tilapia (Oreochromis niloticus) carcass were investigated. The experiments were carried out in an experimental laboratory over 106 d. After sex reversal, 400 early juvenile O. niloticus were tested in a completely randomized experiment with 5 treatments (4 repetitions each), consisting of vitamin E monophosphate supplementation at 0, 50, 100, 150 or 200 mg/kg of a base diet. Treatment diets contained equal amounts of protein and energy. Tilapias supplemented with vitamin E contained arachidonic acid (20:4 omega-6; AA) which participates in inflammatory response. Nile tilapia carcasses that received vitamin E at 100 and 150 mg/kg diet had improved carcass quality by increasing the PUFA:SFA ratio and had the highest levels of polyunsaturated fatty acids from the omega-3 (linolenic acid; 18:3 omega-3) and omega-6 (linoleic acid; 18:2 omega-6) series. (C) 2012 Elsevier Ltd. All rights reserved.

Strategic supplementation of calcium salts of polyunsaturated fatty acids to enhance reproductive performance of Bos indicus beef cows

Five experiments evaluated the effects of supplemental Ca salts of PUFA on reproductive function of Bos indicus beef cows. In Exp. 1, nonlactating and multiparous grazing cows (n = 51) were assigned to receive (as-fed basis) 0.1 kg of a protein-mineral mix + 0.1 kg of ground corn per cow/d, in addition to 0.1 kg per cow/d of 1) Ca salts of PUFA (PF), 2) Ca salts of SFA (SF), or 3) kaolin (control). Treatments were offered from d 0 to 20 of the estrous cycle. No treatment effects were detected on serum progesterone concentrations (P = 0.83), day of luteolysis (P = 0.86), or incidence of short cycles (P = 0.84). In Exp. 2, nonlactating and multiparous grazing cows (n = 43) were assigned to receive PF, SF, or control from d 0 to 8 of the estrous cycle. on d 6, all cows received (intramuscularly) 25 mg of PGF(2 alpha). No treatment effects were detected on serum progesterone concentrations on d 6 (P = 0.37), and incidence (P = 0.67) or estimated time of luteolysis (P = 0.44). In Exp. 3, twenty-seven lactating and multiparous grazing cows, approximately 30 to 40 d postpartum, were assigned to receive PF or control for 10 d beginning at the first postpartum ovulation. No treatment effects were detected (P = 0.85) on incidence of short cycles. In Exp. 4, lactating and multiparous grazing cows (n = 1,454), approximately 40 to 60 d postpartum, were assigned to receive 1 of the 7 treatments for 28 d after timed AI (TAI; d 0): 1) control from d 0 to 28, 2) SF from d 0 to 14 and then control, 3) PF from d 0 to 14 and then control, 4) SF from d 0 to 21 and then control, 5) PF from d 0 to 21 and then control, 6) SF from d 0 to 28, and 7) PF from d 0 to 28. Cows receiving PF for more than 21 d after TAI had greater (P < 0.01) pregnancy to TAI compared with all other treatments combined (50.4 vs. 42.4%, respectively). In Exp. 5, lactating and multiparous grazing cows (n = 501), approximately 40 to 60 d postpartum, were assigned to receive 1 of the 4 treatments for 21 d after TAI (d 0): 1) PF from d 0 to 14 and then control, 2) control from d 0 to 6 and then PF, 3) control from d 0 to 13 and then PF, and 4) PF from d 0 to 21. Cows receiving PF after d 14 of the experiment had greater (P = 0.02) pregnancy to TAI compared with cows not receiving PF during the same period (46.8 vs. 33.1%, respectively). In summary, supplemental Ca salts of PUFA during the expected time of luteolysis increased pregnancy to TAI in beef cows.

Effects of calcium salts of polyunsaturated fatty acids on productive and reproductive parameters of lactating Holstein cows

Two experiments evaluated milk production, serum progesterone and insulin, and reproductive performance of lactating Holstein cows receiving or not receiving Ca salts of polyunsaturated fatty acids (PUFA), or receiving Ca salts of PUFA at different daily frequencies. In experiment 1, 1,125 cows randomly distributed in 10 freestall barns were enrolled. Barns were assigned randomly to receive a high-concentrate diet containing (PI?) or not containing (control, CON) 1.1% (dry matter basis) Ca salts of PUPA. Diets were offered 6 times daily, whereas the Ca salts of PUFA were included in the PF treatment in the first feeding of the day. In experiment 2, 1,572 cows were randomly distributed in 10 freestall barns, which were assigned randomly to receive a diet similar to PF, but with Ca salts of PUFA included only in the first feeding of the day (PF1X), or equally distributed across all 6 feedings (PF6X). During both experiments, cows were artificially inseminated 12 h after the onset of estrus. Once per month, cows that did not conceive to artificial insemination were assigned to a fixed-time embryo transfer protocol. Pregnancy was determined via transrectal ultrasonography 28 and 60 d after expected ovulation. Pregnancy loss was considered in cows that were pregnant on d 28 but nonpregnant on d 60. During both experiments, feed intake, milk yield, and milk protein and fat content were recorded weekly. Blood samples were collected concurrently with embryo transfer. During experiment 1, feed intake was similar between treatments. Compared with CON, PF cows had greater milk yield (37.8 vs. 35.3 kg/d), and reduced milk fat content (3.41 vs. 3.55%). However, PF cows had reduced pregnancy losses per service compared with CON (12.6 vs. 18.3%). Serum progesterone was greater and serum insulin tended to be greater in primiparous cows receiving PF compared with CON cohorts (4.50 vs. 3.67 ng of progesterone/mL, and 10.4 vs. 7.5 mu UI of insulin/mL). During experiment 2, no treatment effects were detected for feed intake, milk yield, or milk fat, whereas PF1X cows tended to have reduced pregnancy losses per service compared with PF6X (14.4 vs. 18.4%). In summary, feeding Ca salts of PUFA to dairy cows increased milk production, did not alter feed intake, and reduced pregnancy losses per service. Further, the total daily amount of Ca salts of RITA should be fed during the first feeding of the day to optimize its benefits on pregnancy maintenance of dairy cows.

Fullerene and omega-3 and omega-6 fatty acids on fish brain antioxidant status

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of low doses of polyunsaturated fatty acids on the attention deficit/Hyperactivity disorder of children: A systematic review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of feeding whole linseed as a source of polyunsaturated fatty acids on performance and egg characteristics of laying hens kept at high ambient temperature

The present study was conducted to evaluate the effects of feeding whole linseed on the laying performance and egg characteristics in laying hens kept at high ambient environmental temperatures (average 34 degrees C; the diurnal temperature range 26 degrees C to 41 degrees C). Two hundred and forty 38-wk-old white Leghorn laying hens were fed diets containing 0, 5, 10 or 15% whole linseed (as a source of n-3 polyunsaturated fatty acids) for a period of 12 weeks. Egg production was recorded daily, while feed intake and egg characteristics were monitored on weekly basis. The results of the study demonstrated that egg production and feed intake decreased, while feed conversion ratio (FCR) per dozen of eggs increased (p <= 0.05) with increasing dietary linseed levels. Egg weight, yolk weight, albumen height, eggshell weight, and eggshell thickness were not influenced (p > 0.05) by linseed levels in the diets offered to the laying hens. The results of the present trial suggest that feeding linseed to the laying hens in hot climates has no detrimental effects on egg characteristics, but has suppressive effects on egg production, feed intake and feed efficiency of laying hens.

Effects of supplementation of calcium salts of polyunsaturated fatty acids on serum concentrations of progesterone and insulin of pregnant dairy cows

Forty-five non-lactating, pregnant Holstein animals (18 heifers and 27 multiparous cows; BW = 561 +/- 114 kg; BCS = 2.9 +/- 0.3; days pregnant = 110 +/- 56 d) were stratified by initial BW and BCS, and randomly assigned to receive daily (as-fed basis) 0.50 kg of ground corn plus 0.22 kg of kaolin (CON), calcium salts of saturated fatty acids (SFA) or polyunsaturated fatty acids (PF) for 14 d. Blood samples were collected on days 0, 7 and 14, immediately prior to (0 h) and 3, 6, 9 and 12 h after feeding, to determine the serum concentrations of P 4 and insulin. No treatment effects were detected for serum concentrations of P 4 (5.52, 6.13 and 5.63 +/- 0.41 ng/mL for CON, SFA and PF, respectively). No treatment effects were detected for serum concentrations of insulin (11.5, 10.5 and 10.1 +/- 1.43 mu IU/mL for CON, SFA and PF, respectively). Heifers had greater serum concentrations of P 4 than multiparous cows (6.35 vs. 5.16 +/- 0.42 ng/mL), but lower serum concentrations of insulin (7.0 vs. 14.4 +/- 1.49 mu IU/mL). Feeding 0.22 kg of calcium salts of polyunsaturated fatty acids is not sufficient to increase the serum concentrations of P 4 and insulin of non-lactating, pregnant dairy cows.

Continuous enzymatic interesterification of milkfat with soybean oil produces a highly spreadable product rich in polyunsaturated fatty acids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.

Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.

Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins.

The effects of free polyunsaturated fatty acids (PUFA) on the binding of ligands to receptors on voltage-sensitive Na+ channels of neonatal rat cardiac myocytes were assessed. The radioligand was [benzoyl-2,5-(3)H] batrachotoxinin A 20alpha-benzoate ([(3)H]BTXB), a toxin that binds to the Na+ channel. The PUFA that have been shown to be antiarrhythmic, including eicosapentaenoic acid (EPA; C20:5n-3), docosahexaenoic acid (DHA; C22:6n-3), eicosatetraynoic acid (ETYA), linolenic acid (C18:3n-3), and linoleic acid (C18:2n-6), inhibited [(3)H]BTXB binding in a dose-dependent fashion with IC50 values of 28-35 microM, whereas those fatty acids that have no antiarrhythmic effects including saturated fatty acid (stearic acid, C18:0), monounsaturated fatty acid (oleic acid; C18:1n-9), and EPA methyl ester did not have a significant effect on [(3)H]BTXB binding. Enrichment of the myocyte membrane with cholesterol neither affected [(3)H]BTXB binding when compared with control cells nor altered the inhibitory effects of PUFA on [(3)H]BTXB binding. Scatchard analysis of [(3)H]BTXB binding showed that EPA reduced the maximal binding without altering the Kd for [(3)H]BTXB binding, indicating allosteric inhibition. The inhibition by EPA of [(3)H]BTXB binding was reversible (within 30 min) when delipidated bovine serum albumin was added. The binding of the PUFA to this site on the Na+ channel is reversible and structure-specific and occurs at concentrations close to those required for apparent antiarrhythmic effects and a blocking effect on the Na+ current, suggesting that binding of the PUFA at this site relates to their antiarrhythmic action.

Quality of polyunsaturated fatty acids in Nile tilapias (Oreochromis niloticus) fed with vitamin E supplementation

Freshwater fish are an important source of protein, but they also contain other highly nutritive components such as fats. Polyunsaturated fatty acids (PUFAs) are essential for normal growth, development and reproduction of vertebrates. The antioxidant role of vitamin E in cell membranes prevents fatty acid and cholesterol oxidation, thereby promoting PUFA and subcellular particle stabilization. The effects of vitamin E supplementation on the quality of Nile tilapia (Oreochromis niloticus) carcass were investigated. The experiments were carried out in an experimental laboratory over 106 d. After sex reversal, 400 early juvenile O. niloticus were tested in a completely randomized experiment with 5 treatments (4 repetitions each), consisting of vitamin E monophosphate supplementation at 0, 50, 100, 150 or 200 mg/kg of a base diet. Treatment diets contained equal amounts of protein and energy. Tilapias supplemented with vitamin E contained arachidonic acid (20:4 omega-6; AA) which participates in inflammatory response. Nile tilapia carcasses that received vitamin E at 100 and 150 mg/kg diet had improved carcass quality by increasing the PUFA:SFA ratio and had the highest levels of polyunsaturated fatty acids from the omega-3 (linolenic acid; 18:3 omega-3) and omega-6 (linoleic acid; 18:2 omega-6) series. (C) 2012 Elsevier Ltd. All rights reserved.

Antioxidant properties in cashew apple byproduct (Anacardium occidentale L.): effect on lipoperoxidation and on the polyunsaturated fatty acids profile in rats

The cashew apple (Anacardium occidentale L.) contains phenolic compounds usually related with antioxidant properties. Then, the aim of this study was to investigate its antioxidant capacity. The antioxidant capacity of the hydroalcoholic extract of the cashew apple pulp (EHAlc.) was assessed for the scavenging of the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) by in vitro method and by an in vivo essay. For this essay a 30-day oral (gavage, EHAlc. 200 and 400 mg/kg) study was conducted in Wistar male rats, evaluating hepatic, plasma and brain tissues. In DPPH model, the extract demonstrated antioxidant activity of 95% (largest concentration, 1000 mu g/mL). There were found no relevant peroxidation comparing the treated animals with the control group. However, the treated group presented a lower level of brain lipoperoxidation. Also in the treated animals brain tissue was found the largest amount of polyunsaturated fatty acids (PUFA), mainly docosahexaenoic (DHA). Therqfore, the analyzed extract from cashew apple pulp clone CCP-76 contains effective natural antioxidants, responsible for free radical scavenging in vitro and also for decreasing the brain lipoperoxidation and keeping the PUFAS levels in Wistar rats.

Synthesis of hydroperoxide and perketal derivatives of polyunsaturated fatty acids as potential antimalarial agents

Hydroperoxide derivatives of beta-oxa-substituted polyunsaturated fatty acids were prepared by 15-lipoxygenase catalysed oxidation and perketal derivatives of fatty acid hydroperoxides were synthesized. The perketals are more stable than their parent fatty acid hydroperoxides, but less active as antimalarial agents in the in vitro growth inhibition of Plasmodium falciparum. (C) 1998 Elsevier Science Ltd. All rights reserved.