Fatty acids and CHD

During the last century much evidence has accumulated to suggest that from a public health perspective the type of fat is more important than the amount of fat. Saturated and trans-fatty acids increase and both n-6 and n-3 PUFA decrease the risk of CHD. Most of the knowledge about the effects of dietary fatty acids on CHD risk is based on observational studies and controlled dietary experiments with intermediate end points (e.g. blood lipoprotein fractions). Information from high-quality randomised controlled trials on fatty acids and CHD is lacking. The Netherlands Institute for Public Health has calculated the potential health gain that can be achieved if the fatty acid composition of the current Dutch diet is replaced by the recommended fatty acid composition. The recommendations of The Netherlands Health Council are: saturated fatty acids

Platelet Redox Balance in Diabetic Patients with Hypertension improved by n-3 fatty acids

OBJECTIVE:
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance.
RESEARCH DESIGN AND METHODS:
We randomized hypertensive T2DM patients (T2DM HT; n = 22) and age-and-sex matched hypertensive study participants without diabetes (HT alone; n = 23) in a double-blind, crossover fashion to receive 8 weeks of n-3 PUFAs (1.8 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid) or identical olive oil capsules (placebo), with an intervening 8-week washout period. Platelet nitrite and superoxide were measured and compared before and after treatment; 8-isoprostane was determined by ELISA and subcellular compartmentalization of the NAD(P)H oxidase subunit p47-phox examined by Western blotting.
RESULTS:
The n-3 PUFA supplementation reduced 8-isoprostane and superoxide levels in platelets from T2DM HT, but not HT alone, participants, without effect on nitrite production. This coincided with a significant decrease in p47-phox membrane localization and a similar reduction in superoxide to that achieved with apocynin. At baseline, a subcohort of T2DM HT and HT alone participants showed evidence of nitric oxide synthase (NOS)-derived superoxide production, indicating defective enzymatic activity. This was reversed significantly in T2DM HT participants after treatment, demonstrating improved NOS function.
CONCLUSIONS:
Our finding that n-3 PUFAs diminish platelet superoxide production in T2DM HT patients in vivo suggests a therapeutic role for these agents in reducing the vascular-derived oxidative stress associated with diabetes.

Long-chain haloalkanes are incorporated into fatty-acids by Rhodococcus rhodochrous NCIMB-13064

The fatty acid composition of the cellular lipids of Rhodococcus rhodochrous NCIMB 13064 grown on various long-chain haloalkanes has been investigated and the influence of halogen substituents, carbon chain length and the position of halogen substitution in the growth substrate explored. Of the total fatty acids present in cells grown on 1-chloro-, 1-bromo- and 1-iodohexadecane, 75, 90 and 81%, respectively, were substituted in the omega-position by the corresponding halogen but only 1% of the fatty acids present after growth on 1-fluorotetradecane were fluorinated in this position. The extent of the halofatty acid incorporation with different halogen substituents in the growth substrate appears to reflect the degree to which oxygenase attack is restricted to the non-halogenated end of the haloalkane. Studies of the fatty acid composition of cells after growth on a series of 1-chloroalkanes containing an even number of carbon atoms between C-10 and C-18 indicated chlorofatty acid incorporation from C-12 to C-18 substrates at levels ranging from 21% with C-12 to 75% with C-16. The chlorofatty acids formed by initial oxidation of the chloroalkane were chain-lengthened or chain-shortened by from two to eight carbon atoms, with accompanying desaturation in some instances. Substantial quantities of a methyl-branched C-19:0 chlorofatty acid were also present with several chloroalkane substrates, When the fatty acid composition of cells after growth on 1-bromoalkanes containing an odd number of carbon atoms between C-11 and C-17 was examined, the incorporation of bromofatty acids was observed with C-13, C-15 and C-17 substrates; a maximum of 76% was recorded for the C-15 bromoalkane. As with even chain-length chloroalkanes, both chain-lengthening and -shortening occurred predominantly via two-carbon units so that most bromoacids present possessed an odd number of carbon atoms, When 1-bromododecane or 2-bromododecane were substrates, overall incorporations of bromofatty acids into the lipid fraction were very similar, demonstrating that the position of halogen substitution in the haloalkane was not critical in determining the extent of incorporation of the haloacids into cellular lipids. The results of the study indicate a mechanism by which degradation products of chlorinated paraffins could enter the biological food chain.

Synthesis and in Vitro and in Vivo Evaluation of a Series of Dihydroisocoumarin Derivatives Conjugated with Fatty Acids, Alcohols, and Amines as Potential Anticancer Agents

In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues Conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to (he dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds Conjugated with gamma-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1.3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo ill a number of human tumor xenograft models.

Examining acute and chronic effects of short- and long-chain fatty acids on peptide YY (PYY) gene expression, cellular storage and secretion in STC-1 cells

PURPOSE: Peptide YY (PYY) is a gastrointestinal hormone with physiological actions regulating appetite and energy homoeostasis. The cellular mechanisms by which nutrients stimulate PYY secretion from intestinal enteroendocrine cells are still being elucidated.

METHODS: This study comprehensively evaluated the suitability of intestinal STC-1 cells as an in vitro model of PYY secretion. PYY concentrations (both intracellular and in culture media) with other intestinal peptides (CCK, GLP-1 and GIP) demonstrated that PYY is a prominent product of STC-1 cells. Furthermore, acute and chronic PYY responses to 15 short (SCFAs)- and long-chain (LCFAs) dietary fatty acids were measured alongside parameters for DNA synthesis, cell viability and cytotoxicity.

RESULTS: We found STC-1 cells to be reliable secretors of PYY constitutively releasing PYY into cell culture media (but not into non-stimulatory buffer). We demonstrate for the first time that STC-1 cells produce PYY mRNA transcripts; that STC-1 cells produce specific time- and concentration-dependent PYY secretory responses to valeric acid; that linoleic acid and conjugated linoleic acid 9,11 (CLA 9,11) are potent PYY secretagogues; and that chronic exposure of SCFAs and LCFAs can be detrimental to STC-1 cells.

CONCLUSIONS: Our studies demonstrate the potential usefulness of STC-1 cells as an in vitro model for investigating nutrient-stimulated PYY secretion in an acute setting. Furthermore, our discovery that CLA directly stimulates L-cells to secrete PYY indicates another possible mechanism contributing to the observed effects of dietary CLA on weight loss.

Selective hydrogenation of fatty acids to alcohols over highly dispersed ReOx/TiO2 catalyst

Production of fatty alcohols through selective hydrogenation of fatty acids was studied over a 4% ReOx/TiO2 catalyst. Stearic acid was hydrogenated to octadecanol at temperatures and pressures between 180-200 degrees C and 2-4 MPa, with selectivity reaching 93%. A high yield of octadecanol was attributed to a strong adsorption of the acid compared to alcohol on the catalyst, which inhibits further alcohol transformation to alkanes. Low amounts (<7%) of alkanes (mainly octadecane) were formed during the conversion of stearic acid. However, it was found that the catalyst could be tuned for the production of alkanes. The reaction intermediates were octadecanal and stearyl stearate. Based on the reaction products analysis and catalyst characterization, a reaction mechanism and possible pathways were proposed.

Short-chain fatty acids cause an IL-8 response in cystic fibrosis airways via increased GPR41

RATIONALE: Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune/inflammatory processes.

OBJECTIVES: To investigate the capacity of anaerobes to contribute to CF airway pathogenesis via SCFAs.

METHODS: Samples from 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFAs levels in anaerobe supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of SCFAs receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings, and 16HBE14o- and CFBE41o- cells were evaluated using RT-PCR, western blot, laser scanning cytometry and confocal microscopy. SCFAs-induced IL-8 secretion was monitored by ELISA.

MEASUREMENTS AND MAIN RESULTS: Fifty seven of 109 (52.3%) PWCF were anaerobe-positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF under (n=24) and over 6 years (n=85). All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic and butyric acid. SCFAs levels were higher in BAL samples from adults than children. GPR41 levels were elevated in; CFBE41o- versus 16HBE14o- cells; CF versus non-CF bronchial brushings; 16HBE14o- cells after treatment with CFTR inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dose-dependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells with a higher production of IL-8 in CFBE41o- than 16HBE14o- cells.

CONCLUSIONS: This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via upregulated GPR41.

Implication of modified molecular structure of lipid through heat-related process to fatty acids supply in Brassica carinata seed.

This study was conducted to explore the effect of different autoclave heating times (30, 60 and 90 min) on fatty acids supply and molecular stability in Brassica carinata seed. Multivariate spectral analyses and correlation analyses were also carried out in our study. The results showed that autoclaving treatments significantly decreased the total fatty acids content in a linear fashion in B. carinata seed as heating time increased. Reduced concentrations were also observed in C18:3n3, C20:1, C22:1n9, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), omega 3 (ω-3) and 9 (ω-9) fatty acids. Correspondingly, the heated seeds showed dramatic reductions in all the peak intensities within lipid-related spectral regions. Results from agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA) indicated that the raw oilseed had completely different structural make-up from the autoclaved seeds in both CH3 and CH2 asymmetric and symmetric stretching region (ca. 2999–2800 cm−1) and lipid ester Cdouble bond; length as m-dashO carbonyl region (ca. 1787–1706 cm−1). However, the oilseeds heated for 30, 60 and 90 min were not grouped into separate classes or ellipses in all the lipid-related regions, indicating that there still exhibited similarities in lipid biopolymer conformations among autoclaved B. carinata seeds. Moreover, strong correlations between spectral information and fatty acid compositions observed in our study could imply that lipid-related spectral parameters might have a potential to predict some fatty acids content in oilseed samples, i.e. B. carinata. However, more data from large sample size and diverse range would be necessary and helpful to draw up a final conclusion.

Effect of polyunsaturated fatty acids (PUFAs) on the proliferation and extracellular matrix mineralization and gene expression of gilthead seabream skeletal cell lines

The aquaculture industry aims at replacing significant amounts of marine fish oil by vegetable oils in fish diet. Dietary lipids have been shown to alter the fatty acid composition of bone compartments, which would impact the local production of factors controlling bone formation. Knowledge on the mechanisms underlying the nutritional regulation of bone metabolism is however scarce in fish. Two in vitro bone-derived cell systems developed from seabream (an important species for aquaculture in the Mediterranean region) vertebra, capable of in vitro mineralization and exhibiting prechondrocyte (VSa13) and pre-osteoblast (VSa16) phenotype, were used to assess the effect of certain polyunsaturated fatty acids (PUFAs; arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids) on cell proliferation, extracellular matrix (ECM) mineralization and gene expression. While all PUFAs promoted morphological changes in both cell lines, VSa16 cell proliferation appeared to be stimulated by PUFAs in a dose dependent manner until 100M, whereas proliferation of VSa13 cells was impaired at concentrations above 10M. AA, EPA and DHA inhibited VSa13 ECM mineralization, alone and in combination, while VSa16 ECM mineralization was only inhibited by AA and EPA. DHA had the opposite effect, increasing mineralization almost by 2 fold. When EFAs were combined, DHA apparently compensated for the inhibitory effect of AA and EPA. Expression of marker genes for bone and lipid metabolisms has been investigated by qPCR and shown to be regulated in pre-osteoblasts exposed to individual PUFAs. Our results show that PUFAs are effectors of fish bone cell lines, altering cell morphology, proliferation and mineralization when added to culture medium. This work also demonstrates the suitability of our in vitro cell systems to get insights into mineralization-related effects of PUFAs in vivo and to evaluate the replacement of fish oils by vegetable oil sources in fish feeds.

Study of the expression of different genes of long-chain polyunsaturated fatty acids (LC-PUFA) metabolism during the early paralarval development of the common octopus (Octopus vulgaris)

Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologias, Universidade do Algarve, 2015

The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth

Objective - The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. Study Design - In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. Result - Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031–0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002–0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125–1.147; P=0.016) in female offspring were found. Conclusion - Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

The Effect of Long-Chain Polyunsaturated Fatty Acids Intake During Pregnancy on Adiposity of Healthy Full-Term Offspring at Birth

OBJECTIVE: The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. STUDY DESIGN: In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. RESULT: Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031-0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002-0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125-1.147; P=0.016) in female offspring were found. CONCLUSION: Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.

The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids.

Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR) α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe(-/-) mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation.

Skeletal muscle fibre-type comparison of whole tissue and subcellular membrane phospholipids and fatty acids

Membranes are dynamic structures that affect cell structure and function. Compositional changes ofmembranes have been shown with the application of a perturbation; however these are limited to whole tissue analysis. The purpose of this thesis was to compare the phospholipid (PL) fatty acid (FA) composition of rat whole muscle (Wm) to 1) purified and non-purified subsarcolemmal (SS) mitochondria in soleus, plantaris, and red gastrocnemius, and 2) sarcolemma, transverse-tubules, SS and intermyofibrillar (IMF) mitochondria fix)m whole hindlimb. The major findings were that 1) contamination significantly altered the PL FA composition of the SS mitochondrial membrane fraction, 2) Wm and SS mitochondria compositions differed between muscle types, and 3) Wm did not accurately reflect the PL FA composition of any isolated subcellular membranes, with each being unique from each other. As such, the relevancy of the trends reported in the literature of the effects of perturbations on Wm may be limited.

Investigations on the production of long chain fatty acids in Choanephora cucurbitarum (Berk.

The fatty acid composition of the total cellular lipids of Choanephora cucurbitarum incubated for 96 hrs on either glucose-ammonium sulfate or malt-weast extract media was determined. The major fatty acids were palmitic, palmitoleic, stearic and linoleic acids. The saturated fatty acid possessing the longest acyl chain was stearate (C 18:0). The presence of glutamic acid (2.0 x 10-1% or 1.36 x la-2M) in either of the above growth media resulted in increase in percent of 1f-linolenic acid, decrease in percent of linoleic ~iCid and appearance of a new series of fatty acid> C ~8 e.g. C ",,,,'V' C2k:O, C26,O. The addition of glutamic acid had no effect on the lipid yield but slightly decreased the degree of unsaturation. Compounds which duplicated the effect of glutamic acid were acetate, malate, citrate, succinate, 0( -ketoglutarate, prOline, -y -aminobutyric acid and glucose (3%) but not aspartic acid or alanine. ~o correlation was found between glutamic acid pool concentration and the presence in the growth medium of those compounds which stimulate long chain fatty acid production. Four hours of incubation with 27 JJ 1-1 glutamate supported the production of long chain fatty acids. This stimulation is inhibited if 272 .u M isophthalic acid is added with 27 AJ M glutamate. But, long chain fatty acids were detected when 27 JJ M eX -ketoglutarate is also present in the incubation mixture. Five hours of incubation with 100 ,Mg/ml of cycloheximide resulted in over 9CY/o inhibition of cytoplasmic :protein synthesise Glutamate (27 .uM) enhanced the synthesis of long chain fatty acids under these conditions. These findings are discussed in an attempt to provide a plausible explanation COmmon to compounds that support the production of long chain fatty acids.