Alteration of Fatty Acid Profile in Fragile X Syndrome

Fragile X Syndrome (FXS) is the most prevalent monogenic cause of Autism Spectrum Disorders (ASDs). Despite a common genetic etiology, the affected individuals display heterogenous metabolic abnormalities including hypocholesterolemia. Although changes in the metabolism of fatty acids (FAs) have been reported in various neuropsychiatric disorders, it has not been explored in humans with FXS. In this study, we investigated the FA profiles of two different groups: (1) an Argentinian group, including FXS individuals and age- and sex-matched controls, and (2) a French-Canadian group, including FXS individuals and their age- and sex-matched controls. Since phospholipid FAs are an indicator of medium-term diet and endogenous metabolism, we quantified the FA profile in plasma phospholipids using gas chromatography. Our results showed significantly lower levels in various plasma FAs including saturated, monosaturated, ω-6 polyunsaturated, and ω-3 polyunsaturated FAs in FXS individuals compared to the controls. A decrease in the EPA/ALA (eicosapentaenoic acid/alpha linoleic acid) ratio and an increase in the DPA/EPA (docosapentaenoic acid/eicosapentaenoic acid) ratio suggest an alteration associated with desaturase and elongase activity, respectively. We conclude that FXS individuals present an abnormal profile of FAs, specifically FAs belonging to the ω-3 family, that might open new avenues of treatment to improve core symptoms of the disorder.     

Improved synthesis and characterization of saturated branched‐chain fatty acid isomers

The development of viable technologies for producing green products from renewable fats and oils is highly desirable since such materials can serve as replacements for non‐renewable and poorly biodegradable petroleum‐based products. Mixtures of saturated branched‐chain fatty acid isomers (sbc‐FAs), commonly referred to as isostearic acid, are important intermediates for the production of biodegradable lubricants, cosmetics, emollients, and hydraulic fluids. Present methods for producing sbc‐FAs, however, often give low yields of sbc‐FAs or sbc‐FA preparations with a high content of dimer acid fatty acid co‐products. This study reports an improved route to synthesizing sbc‐FAs from monounsaturated fatty acids using a modified H‐Ferrierite zeolite catalyst in conjunction with small amounts of triphenylphosphine additive. The yields of sbc‐FAs (up to 80 wt%) and co‐products (up to15 wt%) were determined using a modification of a previously reported GC method. A more detailed analysis of the distribution of sbc‐FA isomers in the products was made by the combined use of GC × GC‐TOF‐MS. Additionally, it was found that the H‐Ferrierite zeolite catalyst was recyclable and reusable up to 10 times without significant loss of activity and selectivity for sbc‐FAs.     

Dietary Fatty‐Acid Compositions Are more Strongly Reflected in Fatty than Lean Dorsal Fillets of Common Carp (Cyprinus carpio L.)

In this fish‐feeding study, we tested similarity patterns between fatty acids (FA) in diets and common carp (Cyprinus carpio) of fish ponds used for semi‐intensive aquaculture, containing naturally occurring pond zooplankton and different feeds (marine or terrestrial feeds) until carp reached market size. We evaluated if and how total lipid contents in dorsal fillets can reflect dietary FA compositions in farm‐raised common carp and hypothesized that increasing total lipid contents in dorsal fillets significantly increase the similarity between dietary and dorsal fillets’ FA compositions. Results of this study showed that carps had higher total lipids when supplied with marine feeds and dietary FA compositions were indeed more strongly reflected in fatty (i.e. high total lipid contents) than in leaner dorsal fillets (low total lipid contents). Increasing total lipid contents in dorsal fillets significantly increased the similarity between the dietary and dorsal fillets’ FA compositions. In contrast, leaner dorsal fillets had FA patterns that were more distinct from dietary FA. Total lipid contents higher than ~60 mg/g dry weight in dorsal fillets had only limited effects on increasing the similarity between FA compositions of diets and dorsal fillets, and were independent of feed sources. It is thus suggested that higher total lipid contents in dorsal fillets can be used as a proxy to predict dietary FA profiles in common carps, or perhaps even in farm‐raised fish in general.     

Fatty Acid Synthesis in Glial Cells of the CNS

Fatty acids (FAs) are of crucial importance for brain homeostasis and neural function. Glia cells support the high demand of FAs that the central nervous system (CNS) needs for its proper functioning. Additionally, FAs can modulate inflammation and direct CNS repair, thereby contributing to brain pathologies such Alzheimer’s disease or multiple sclerosis. Intervention strategies targeting FA synthesis in glia represents a potential therapeutic opportunity for several CNS diseases.     

Zeolite‐catalyzed isomerization of oleic acid to branched‐chain isomers

Branched‐chain (bc) saturated fatty acids (SFA) have potential as oleochemical intermediates since they have better oxidative stability than linear unsaturated fatty acids (UFA) and have better low‐temperature properties than linear SFA. Previous studies in converting UFA to bc‐FA using clay catalysts have resulted in only modest yields and conversions. Recent reports, however, have suggested that certain zeolites can be effective catalysts for converting UFA to bc‐FA in higher yields and conversions. In this work, we examined the scope and potential of the zeolite‐catalyzed synthesis of bc‐FA starting from readily available monounsaturated linear FA. Our results show that common UFA such as oleic acid can be converted to bc‐isomers using modified Ferrierite zeolite catalysts with high conversions (98%) and high selectivity (85%) and that the zeolite catalysts are reusable for at least three cycles. The positions of branching (methyl) on the FA chain were determined from the GC‐MS spectra of the picolinyl esters of the bc‐FA.     

A comparative study of fatty acid profiles in ruminant and non‐ruminant milk

This is a comprehensive study of fatty acid (FA) profiles in milk from bovine, caprine, ovine, asine, and equine species. Milks from these species are universally common as constituents in a variety of different food and dairy products. We have obtained structural information on FAs, and discussed their correlation to health effects. The extracted fat from all species were derivatized to FA methyl esters for analysis by GC‐MS. Large differences in the lipid content and FA composition between ruminants and non‐ruminants were observed. Ovine milk showed the highest lipid content of all the animals tested, both ruminants and non‐ruminants. Among the ruminants, bovine milk was richer in saturated FAs (69.7%) than ovine‐ and caprine milk (57.5 and 59.9%, respectively). Ovine milk contained the highest amounts of monounsaturated FAs (39.1%) and also odd‐ and branched‐chain FAs (5.5%). Milk from the monogastric animals, mares and donkeys, were highest in polyunsaturated FAs with a content of 19.3 and 14.2%, respectively. The assumed health negative trans FAs were analyzed to be highest in the ruminant milk (0.7–1.0%). Milk from these species contained also the highest amount of the health beneficial CLA (0.4–0.7%). Practical applications: This is a comprehensive study of milk from five species analyzed under identical conditions. The different fatty acids and their derivatives are increasingly important components because of the contradictory reports on positive and negative effects on human health. New information on the composition of milk from different species is of great importance. The results may give valuable information to producers and nutritional advisors on the consumption of milk and milk products.     

Individual trans 18:1 Isomers are Metabolised Differently and Have Distinct Effects on Lipogenesis in 3T3‐L1 Adipocytes

The objective of this research was to study the metabolism of individual trans fatty acids (FAs) that can be found in ruminant fat or partially hydrogenated vegetable oils (PHVO) and determine their effects on FA composition and lipogenic gene expression in adipocytes. Differentiated 3T3‐L1 adipocytes were treated with 200 µM of either trans‐9‐18:1, trans‐11‐18:1, trans‐13‐18:1, cis‐9‐18:1 or BSA vehicle control for 120 h. Trans‐9‐18:1 increased total cell FA content (µmole/well) compared to other FA treatments, which was mainly related to the accumulation of trans‐9‐18:1 in the cells. Adipocytes were able to desaturate a significant proportion of absorbed trans‐11‐18:1 and trans‐13‐18:1 (~20 and 30 % respectively) to cis‐9,trans‐11‐18:2 and cis‐9,trans‐13‐18:2, whereas trans‐9‐18:1 was mostly incorporated intact resulting in a greater lipophilic index (i.e. decreased mean FA fluidity) of adipocytes. Trans‐9‐18:1 up‐regulated (P < 0.05) the expression of lipogenic genes including acetyl‐CoA carboxylase (1.65 fold), FA synthase (1.45 fold), FA elongase‐5 (1.52 fold) and stearoyl‐CoA desaturase‐1 (1.49 fold), compared to the control, whereas trans‐11‐18:1 and trans‐13‐18:1 did not affect the expression of these genes compared to control. Our results suggest that the metabolism and lipogenic properties of trans‐11‐18:1 and trans‐13‐18:1, typically the most abundant trans FA in beef from cattle fed forage‐based diets, are similar and are different from those of trans‐9‐18:1, the predominant trans FA in PHVO.     

Bioorthogonal Chemical Reporters for Monitoring Unsaturated Fatty‐Acylated Proteins

Dietary unsaturated fatty acids, such as oleic acid, have been shown to be covalently incorporated into a small subset of proteins, but the generality and diversity of this protein modification has not been studied. We synthesized unsaturated fatty‐acid chemical reporters and determined their protein targets in mammalian cells. The reporters can induce the formation of lipid droplets and be incorporated site‐specifically onto known fatty‐acylated proteins and label many proteins in mammalian cells. Quantitative proteomics analysis revealed that unsaturated fatty acids modify similar protein targets to saturated fatty acids, including several immunity‐associated proteins. This demonstrates that unsaturated fatty acids can directly modify many proteins to exert their unique and often beneficial physiological effects in vivo.     

Plasma Unesterified Fatty‐Acid Profile Is Dramatically and Acutely Changed under Ischemic Stroke in the Mouse Model

Although plasma biomarkers would facilitate rapid and accurate diagnosis of ischemic stroke for immediate treatment, no such biomarkers have been developed to date. In the present study, we tested our hypothesis that plasma unesterified fatty acids (FFA) are altered at early stages of acute ischemic stroke. Plasma was collected from mice 2 h after the permanent middle cerebral artery occlusion (pMCAo) onset, as well as from sham operated and control animals. After 2 h, pMCAo significantly changed the plasma FFA profile with the most dramatic 2‐ to 3‐fold relative increase in very long n‐3 and n‐6 FFA including 20:4n‐6, 22:4n‐6, 22:5n‐6, and 22:6n‐3. Changes in the plasma FFA profile are consistent with FFA liberation from brain phospholipid hydrolyzed under ischemic insult. These results identify, for the first time, the plasma FFA profile as a potential biomarker for an early ischemic stroke within the therapeutic window for thrombolytic treatment. Further studies are required to confirm its specificity and sensitivity in clinical settings.     

Fatty acid profiles of 80 vegetable oils with regard to their nutritional potential

The current concern for fat intake in western countries has raised the question of the individual fatty acid (FA) impact on health. This important issue has strengthened the awareness of nutritionists and food manufacturers for the control of the FA profile of food products. The aim of this review is to provide a classification of the FA profiles of 80 vegetable oil sources, according to their nutritional potential. The first part of the review focuses on lipoprotein metabolism, and on the impact of each dietary FA on blood lipid composition (LDL‐cholesterol, HDL‐cholesterol and circulating triacylglycerols). In the second part of the review, the oil sources are clustered by similar FA profiles, and the classification is discussed with regard to the individual FA action on blood lipid composition. Apart from the major vegetable seeds, the clustering highlighted some interesting nutritional oil sources containing mainly α‐linolenic acid (camelina, linseed, perilla and stock oils), or interesting amounts of the two essential FA (purslane, chia, raspberry seed, sea buckthorn seed and salicorn oils). Furthermore, this classification provides a useful tool for the formulation of the FA profile of food products.     

Unbound DHA causes a high blank value in β‐oxidation assay: a concern for in vitro studies

The information on binding capacity of different fatty acids (FAs) to albumin is incomplete, however, in the majority of in vitro experiments, FAs and albumin were simply mixed and their affinity believed to be complete. In this study, seven [1‐¹⁴C] FAs were mixed with albumin and assayed for β‐oxidation in rat liver homogenates. In the process of identifying the radioactive background of control assay by LCMS/MS, the results indicated different binding capacity of FAs to albumin. The percentage of unbound FAs recovered in clarified acidic solution was lower than 2% with 16:0 and 18:1n‐9, nearly 5% with EPA, 7% with 18:2n‐6, 18:3n‐3 and 20:4n‐6, and surprisingly high to 41% with DHA. Various FA/albumin molar ratios as well as different types of albumin only marginally affected these data. Thus, the big mass of unbound free DHA led to a high blank value, which is 60 times higher than the real value in the procedure of β‐oxidation measurement in vitro. In the design of future FA research in vitro, the binding capacity of FA to albumin or other proteins must be considered, especially for DHA research.     

Elongation of very Long-Chain (>C<Subscript>24</Subscript>) Fatty Acids in <Emphasis Type="Italic">Clarias gariepinus</Emphasis>: Cloning,Functional Characterization and Tissue Expression of <Emphasis Type="Italic">elovl4</Emphasis> Elongases

Elongation of very long‐chain fatty acid 4 (Elovl4) proteins participate in the biosynthesis of very long‐chain (>C₂₄) saturated and polyunsaturated fatty acids (FA). Previous studies have shown that fish possess two different forms of Elovl4, termed Elovl4a and Elovl4b. The present study aimed to characterize both molecularly and functionally two elovl4 cDNA from the African catfish Clarias gariepinus. The results confirmed that C. gariepinus possessed two elovl4‐like elongases with high homology to two previously characterized Elovl4 from Danio rerio, and thus they were termed accordingly as Elovl4a and Elovl4b. The C. gariepinus Elovl4a and Elovl4b have open reading frames (ORF) of 945 and 915 base pairs, respectively, encoding putative proteins of 314 and 304 amino acids, respectively. Functional characterization in yeast showed both Elovl4 enzymes have activity towards all the PUFA substrates assayed (18:4n‐3, 18:3n‐6, 20:5n‐3, 20:4n‐6, 22:5n‐3, 22:4n‐6 and 22:6n‐3), producing elongated products of up to C₃₆. Moreover, the C. gariepinus Elovl4a and Elovl4b were able to elongate very long‐chain saturated FA (VLC‐SFA) as denoted by increased levels of 28:0 and longer FA in yeast transformed with elovl4 ORF compared to control yeast. These results confirmed that C. gariepinus Elovl4 play important roles in the biosynthesis of very long‐chain FA. Tissue distribution analysis of elovl4 mRNAs showed both genes were widely expressed in all tissues analyzed, with high expression of elovl4a in pituitary and brain, whereas female gonad and pituitary had the highest expression levels for elovl4b.     

Fatty Acid Composition of Tropical Fish Depends on Reservoir Trophic Status and Fish Feeding Habit

Eutrophication results in a deficiency of n‐3 LC‐PUFA (long‐chain polyunsaturated fatty acids) in aquatic food chains, affecting fish nutrition and physiology. The trophic transfer of FA (fatty acids) to fish species of different feeding habits was investigated in two reservoirs in southeast Brazil—the mesotrophic Ponte Nova Reservoir (PN) and the hypereutrophic Billings Reservoir (Bil). Total FA profile of stomach contents and adipose tissue, triacylglycerols (TAG), and phospholipids (PL) from liver and muscle of the omnivorous Astyanax fasciatus and the carnivorous Hoplias malabaricus were analyzed by gas chromatography. A prevalence of n‐6PUFA, as 18:2n‐6 (linoleic acid) and 20:4n‐6 (arachidonic acid, ARA) was observed in the stomach contents and in the tissues of A. fasciatus from the PN reservoir. In contrast, n‐3 LC‐PUFA, as 20:5n‐3 (eicosapentaenoic acid, EPA) was accumulated in fish tissues from Bil, resulting in higher n3/n6 and EPA/ARA ratios, compared to fish from PN. This differential FA accumulation was also observed for H. malabaricus, but differences were slightly minor, and no changes were observed in the EPA/ARA ratios between fish from both reservoirs. Regardless reservoir, FA profiles of TAG resembled that of their diet, whereas FA profiles of PL were more conservative and mainly comprised by LC‐PUFA. We conclude that reservoir trophic status affected the FA composition of food resources available to these fish species, resulting in differential allocation of n‐3 and n‐6 FA. As expected, FA profile of the investigated fish species also reflected their feeding habit and physiological demands.     

Significance of Coprophagy for the Fatty Acid Profile in Body Tissues of Rabbits Fed Different Diets

Four groups of eight New Zealand hybrid rabbits were fattened with ad libitum access to the following pelleted experimental diets: ryegrass meal or alfalfa meal fed either alone or with oats meal in a ratio of 1:1. After 25 weeks they were slaughtered and dissected. Fatty acid (FA) profiles of caecotrophs (re-ingested fermentation products of the caecum), perirenal adipose tissue and intramuscular fat in the Musculus quadriceps were determined. With high proportions of branched-chain FA (BFA) and trans FA, and increased proportions of saturated FA relative to the diets, the caecotroph FA profile showed a clear fingerprint of anaerobe microbial lipid metabolism including biohydrogenation. By contrast, the FA profiles of adipose and lean tissue comprised high proportions of polyunsaturated FA (PUFA), whilst BFA and trans FA occurred in much lower proportions compared to the caecotrophs. Thus, coprophagy did not substantially modify the FA composition of the tissues investigated. Use of forage-only diets, compared to the oats supplemented diets, led to extraordinary high proportions of n-3 PUFA (including 18:3 and long-chain n-3) in the fat of adipose (21.3 vs. 6.7%) and lean tissue (15.4 vs. 5.7%). The forage type diet (grass vs. alfalfa) had smaller effects on the FA profiles. Indications of diet effects on endogenous desaturation, chain elongation and differential distribution of functional FA between the two tissues investigated were found.     

Fatty Acid Composition of Seeds From Wild and Cultivated Ginseng (Panax ginseng Meyer): Occurrence of a High Level of Petroselinic Acid

The lipid content and fatty acid (FA) composition of seeds from the Asian ginseng Panax ginseng growing naturally in taiga forests of the Russian Far East and seeds from cultivated ginseng were studied in this work. The total lipid content of seeds from both wild and cultivated plants was 9–12 % of fresh weight. FA were analyzed as isopropyl esters on a polar capillary column BD‐225, which allows good separation of petroselinic and oleic acids. The structure of FAs was confirmed using GC–MS of fatty acid methyl ester (FAME) and 4,4‐dimethyloxazoline derivatives. In all the seed samples, the major FA was petroselinic acid 18:1(n‐12) which comprised more than 60 %; the contents of oleic and linoleic acids were lower (15–17 and 15–16 %, respectively). Earlier, a higher level (>80 %) of oleic acid had been reported for ginseng seeds. This discrepancy can be explained by an insufficient separation of these acids on standard columns used for GC of FAME. In general, seeds of wild and cultivated ginseng are very similar in lipid content and FA composition.     

Perspectives on Potential Fatty Acid Modulations of Motility Associated Human Sperm Ion Channels

Human spermatozoan ion channels are specifically distributed in the spermatozoan membrane, contribute to sperm motility, and are associated with male reproductive abnormalities. Calcium, potassium, protons, sodium, and chloride are the main ions that are regulated across this membrane, and their intracellular concentrations are crucial for sperm motility. Fatty acids (FAs) affect sperm quality parameters, reproductive pathologies, male fertility, and regulate ion channel functions in other cells. However, to date the literature is insufficient to draw any conclusions regarding the effects of FAs on human spermatozoan ion channels. Here, we aimed to discern the possible effects of FAs on spermatozoan ion channels and direct guidance for future research. After investigating the effects of FAs on characteristics related to human spermatozoan motility, reproductive pathologies, and the modulation of similar ion channels in other cells by FAs, we extrapolated polyunsaturated FAs (PUFAs) to have the highest potency in modulating sperm ion channels to increase sperm motility. Of the PUFAs, the ω-3 unsaturated fatty acids have the greatest effect. We speculate that saturated and monounsaturated FAs will have little to no effect on sperm ion channel activity, though the possible effects could be opposite to those of the PUFAs, considering the differences between FA structure and behavior.     

Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids

Obesity and metabolic syndrome are associated with cognitive decline and dementia. Palmitic acid (PA) is increased in the cerebrospinal fluid of obese patients with cognitive impairment. This study was therefore designed to examine fatty acid (FA) lipotoxicity in BV2 microglia cells. We found that PA induced time- and dose-dependent decrease in cell viability and increase in cell death without affecting the cell cycle profile and that PA lipotoxicity did not depend on cell surface free fatty acid receptors but rather on FA uptake. Treatment with sulfosuccinimidyl oleate (SSO), an irreversible inhibitor of fatty acid translocase CD36, significantly inhibited FA uptake in BSA- and PA-treated cells and blocked PA-induced decrease in cell viability. Inhibition of ER stress or treatment with N-acetylcysteine was not able to rescue PA lipotoxicity. Our study also showed that unsaturated fatty acids (UFAs), such as linoleic acid (LA), oleic acid (OA), α-linolenic acid (ALA), and docosahexaenoic acid (DHA), were not lipotoxic but instead protected microglia against PA-induced decrease in cell viability. Co-treatment of PA with LA, OA, and DHA significantly inhibited FA uptake in PA-treated cells. All UFAs tested induced the incorporation of FAs into and the amount of neutral lipids, while PA did not significantly affect the amount of neutral lipids compared with BSA control.     

Cross‐Linkable Modified Nanocellulose/Polyester Resin‐Based Composites: Effect of Unsaturated Fatty Acid Nanocellulose Modification on Material Performances

Unsaturated fatty acid (FA)–modified nanocellulose (m‐NC) shows potential application in improving mechanical properties of unsaturated polyester/m‐NC nanocomposites (UPe/m‐NC). A polyester matrix is obtained by polycondensation of maleic anhydride and products of poly(ethylene terephthalate) depolymerization with propylene glycol. Two methods of NC modification are performed: direct esterification with oleic acid, linseed, or sunflower oil FAs, and esterification/amidation with maleic acid/ethylene diamine (MA/EDA) bridging group followed by amidation with methyl ester of FAs. Increases of stress at break in the ranges from 148.8% to 181.4% and from 155.8% to193.0% for UPe/m‐NC composites loaded with 1 wt% of NC modified directly or via MA/EDA cross‐linker, respectively, are obtained. Results of the modeling of tensile modulus, by using the Cox–Krenchel model, show good agreement with experimentally obtained data. The effect of FAs' cross‐linking capabilities on the dynamic‐mechanical and thermal properties of the UPe/m‐NC is studied. Cross‐linking density, modulus, and T_g of the nanocomposite show appropriate relation with the unsaturation extent/structure of NC modification.