Influence of monomeric and polymeric structure on the physical properties of thermoplastic polyesters derived from hydroxy fatty acids

The physical properties of three vegetable oil derived medium and long chain poly(-hydroxy fatty ester)s (P(Me--OHFA)s), namely poly(-hydroxynonanoate) [P(Me--OHC9)], poly(-hydroxytridecanoate) [P(Me--OHC13)] and poly(-hydroxyoctadecanoate) [P(Me--OHC18)] (n = 8, 12 and 17, respectively), of the [-(CH2)(n)-COO-](x) polyester homologous series are presented. The effect of M-n (M-n 10-40 kg mol(-1)) and n on the crystal structure and thermal and mechanical properties of the P(Me--OHFA)s were investigated by wide-angle X-ray diffraction (WAXD), TGA, DSC, dynamic mechanical analysis (DMA) and tensile analysis and are discussed in the context of the [-(CH2)(n)-COO-](x) polyester homologous series, contrasted with linear polyethylene (PE). For all P(Me--OHFA)s the WAXD data indicated an orthorhombic crystal phase reminiscent of linear PE with crystallinity (X-c = 50%-80%) depending strongly on M-n. The glass transition temperature and Young's modulus for P(Me--OHFA)s increased with X-c. The DSC, DMA and TGA studies for P(Me--OHFA)s (n = 8, 12 and 17) indicated strong correlations between the melting, glass transition and thermal degradation behavior and n. The established predictive structure relationships can be used for the custom engineering of polyester materials suitable for specialty and commodity applications. (c) 2014 Society of Chemical Industry

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

Enhancement of gilthead sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax) larval growth by dietary vitamin E en relation to diffetent levels of essential fatty acids

[EN]Most marine fish larvae require high amounts of n-3 HUFA (highly unsaturated fatty acids) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Watanabe, 1982; Izquierdo, 1996). Fish larvae tissue lipids are also very high in n-3 HUFA, what implies a higher risk of peroxidation (Sargent et al. 1999) and cellular damage (Kanazawa, 1991), requiring then antioxidants to protect them intra- and extra-cellularly from free radical compounds. Vitamin E (Vit E) functions as a chain breaking antioxidant, reacting with the lipid peroxide radical produced and preventing the further reaction with a new PUFA. Hence their requirements are related with the dietary and tissue PUFA contents. The objective of the present study was to determine the effect of dietary Vit E on gilthead sea bream and sea bass survival, growth and stress, at different n-3 HUFA levels.

Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids.

Purpose It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein. Methods This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months. Results Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups. Conclusions Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

n-fatty acids of shale partings in the Franciscan bedded cherts

Normal saturated fatty acid (n-fatty acid) in marine sediments from coastal and pelagic environments were analyzed. The coastal sediments contain both short-chained n-fatty acids with carbon numbers from 12 to 18 and long-chained acids from 22 to 32, whereas the pelagic sediments contain predominantly short-chained acids. The relative abundance of short-chained to long-chained n-fatty acids, expressed by the molar ratio C16/C26, can be an indicator to assess the depositional environment of sedimentary rocks. The ratio of long-chained n-fatty acids (C22-C32) to the total n-fatty acids also has the potential to discriminate sedimentary environments. The indicators based on the n-fatty acids were applied to the Franciscan bedded cherts. The result shows that the bedded cherts had deposited in continuous environments from the pelagic to the coastal. This is in harmony with the same inference based on major, trace and rare earth elements and normal paraffins.

The helical domain of intestinal fatty acid binding protein is critical for collisional transfer of fatty acids to phospholipid membranes

Fatty acid binding proteins (FABPs) exhibit a β-barrel topology, comprising 10 antiparallel β-sheets capped by two short α-helical segments. Previous studies suggested that fatty acid transfer from several FABPs occurs during interaction between the protein and the acceptor membrane, and that the helical domain of the FABPs plays an important role in this process. In this study, we employed a helix-less variant of intestinal FABP (IFABP-HL) and examined the rate and mechanism of transfer of fluorescent anthroyloxy fatty acids (AOFA) from this protein to model membranes in comparison to the wild type (wIFABP). In marked contrast to wIFABP, IFABP-HL does not show significant modification of the AOFA transfer rate as a function of either the concentration or the composition of the acceptor membranes. These results suggest that the transfer of fatty acids from IFABP-HL occurs by an aqueous diffusion-mediated process, i.e., in the absence of the helical domain, effective collisional transfer of fatty acids to membranes does not occur. Binding of wIFABP and IFABP-HL to membranes was directly analyzed by using a cytochrome c competition assay, and it was shown that IFABP-HL was 80% less efficient in preventing cytochrome c from binding to membranes than the native IFABP. Collectively, these results indicate that the α-helical region of IFABP is involved in membrane interactions and thus plays a critical role in the collisional mechanism of fatty acid transfer from IFABP to phospholipid membranes.

Aspergillus has distinct fatty acid synthases for primary and secondary metabolism

Aspergillus nidulans contains two functionally distinct fatty acid synthases (FASs): one required for primary fatty acid metabolism (FAS) and the other required for secondary metabolism (sFAS). FAS mutants require long-chain fatty acids for growth, whereas sFAS mutants grow normally but cannot synthesize sterigmatocystin (ST), a carcinogenic secondary metabolite structurally and biosynthetically related to aflatoxin. sFAS mutants regain the ability to synthesize ST when provided with hexanoic acid, supporting the model that the ST polyketide synthase uses this short-chain fatty acid as a starter unit. The characterization of both the polyketide synthase and FAS may provide novel means for modifying secondary metabolites.

Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.

Recent evidence indicates that long-chain polyunsaturated fatty acids (PUFAs) can prevent cardiac arrhythmias by a reduction of cardiomyocyte excitability. This was shown to be due to a modulation of the voltage-dependent inactivation of both sodium (INa) and calcium (ICa) currents. To establish whether PUFAs also regulate neuronal excitability, the effects of PUFAs on INa and ICa were assessed in CA1 neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentration-dependent shift of the voltage dependence of inactivation of both INa and ICa to more hyperpolarized potentials. Consequently, they accelerated the inactivation and retarded the recovery from inactivation. The EC50 for the shift of the INa steady-state inactivation curve was 2.1 +/- 0.4 microM for docosahexaenoic acid (DHA) and 4 +/- 0.4 microM for eicosapentaenoic acid (EPA). The EC50 for the shift on the ICa inactivation curve was 2.1 +/- 0.4 for DHA and > 15 microM for EPA. Additionally, DHA and EPA suppressed both INa and ICa amplitude at concentrations > 10 microM. PUFAs did not affect the voltage dependence of activation. The monounsaturated oleic acid and the saturated palmitic acid were virtually ineffective. The combined effects of the PUFAs on INa and ICa may reduce neuronal excitability and may exert anticonvulsive effects in vivo.

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.

Fatty acids as haptens: exploring the limits of antigenicity

Fatty acids (FAs) are relatively small, hydrophobic and highly mobile molecular structures with vital biological functions and a ubiquitous distribution. Surprisingly, however, they can be rendered immunogenic. We have synthesised a novel immunogen in which dicarboxylic linoleic acid was conjugated to a carrier protein. Dicarboxylic fatty acids (DCA) differ from their normal counterparts only by their possession of a carboxyl group at each end of the molecule. When conjugated to proteins as haptens, they are, therefore, presented to the immune system with a free carboxyl group at the distal end, instead of a methyl group. Polyclonal IgG antibodies raised in response to this unique immunogen could bind not only conjugated hapten with high affinity, but also the equivalent free FA in mono and dicarboxylic form. Similar conjugates constructed from normal FAs produced much weaker antibody responses and could scarcely be considered antigenic at all. The cross-reactivities of the anti-DCA antibodies with FA variants differing in the number, position and configuration of their double bonds showed that the antibody paratope (binding site) was structured to accommodate the hapten in a way that depended on the precise shape of the acyl chain. We suggest that FAs become much more effective as B-cell epitopes when presented with their hydrophilic carboxyl group exposed on the surface of immunogenic conjugates. This type of epitope is determined by the particular double bond pattern of the unsaturated acyl chain, as well as the polar head group. (C) 2003 Elsevier Ltd. All rights reserved.

Fatty acids, monocytes and ageing

Elevated free fatty acids (FFA) are a feature of ageing and a risk factor for metabolic disorders such as cardiovascular disease (CVD) and type-2 diabetes (T2D). Elevated FFA contribute to insulin resistance, production of inflammatory cytokines and expression of adhesion molecules on immune cells and endothelial cells, risk factors for CVD and T2D. Molecular mechanisms of FFA effects on monocyte function and how FFA phenotype is affected by healthy ageing remain poorly understood. This thesis evaluated the effects of the two major FFA in plasma, oleate and palmitate on monocyte viability, cell surface antigen expression, and inflammatory activation in THP-1 monocytes. Palmitate but not oleate increased cell surface expression of CD11b and CD36 after 24h, independent of mitochondrial superoxide, but dependent on de novo synthesis of ceramides. LPS-mediated cytokine production in THP-1 monocytes was enhanced and decreased following incubation with palmitate and oleate respectively. In a model of monocyte-macrophage differentiation, palmitate induced a pro-inflammatory macrophage phenotype which required de novo ceramide synthesis, whilst oleate reduced cytokine secretion, producing a macrophage with enhanced clearance apoptotic cells. Plasma fatty acid analysis in young and mid-life populations revealed age-related increases in both the SFA and MUFA classes, especially the medium and very long chain C14 and C24 fatty acids, which were accompanied by increases in the estimated activities of desaturase enzymes. Changes were independently correlated with increased PBMC CD11b, plasma TNF-a and insulin resistance. In conclusion, the pro-atherogenic phenotype, enhanced LPS responses in monocytes, and pro-inflammatory macrophage in the presence of palmitate but not oleate is reliant upon de novo ceramide synthesis. Age-related increases in inflammation, cell surface integrin expression are related to increases in both the MUFA and SFA fatty acids, which in part may be explained by altered de novo fatty acid synthesis.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Omega-3 Fatty Acids are Inversely Related to Callous and Unemotional Traits in Adolescent Boys with Attention Deficit Hyperactivity Disorder

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n−3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous–unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels.

Erythrocyte Phospholipid Molecular Species and Fatty Acids of Down Syndrome Children Compared with Non-affected Siblings

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0–16 : 0, 16 : 0–18 : 1 and 16 : 0–18 : 2n-6, with reduced levels of 16 : 0–20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0–18 : 2n-6 and nearly half the proportion of 16 : 0–20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.