Fatty Acid Chain Length Research Articles

Age-dependent reference intervals in children for the disialoganglioside, GD2, a circulating tumor biomarker for the childhood cancer, neuroblastoma

BackgroundThe disialoganglioside GD2 is a circulating tumor biomarker for the childhood cancer, neuroblastoma. This study establishes reference intervals for GD2 concentration in children within the age range where neuroblastoma commonly occurs. MethodsLeftover plasma samples taken for routine clinical laboratory tests from children without cancer were collected and assayed for the 18-carbon fatty acid chain length lipoform of GD2 using a validated high-pressure liquid chromatography tandem mass spectrometry method with a lower limit of quantification of 3 nM. Samples were stratified into 5 age cohorts (0–6 months, 6–12 months, 12–36 months, 3–10 years and > 10 years). Non-parametric statistical methods were used to define the upper bound of the reference interval for each age cohort. ResultsGD2 was measurable in 90% of samples from children < 10 years of age and GD2 concentration was age-dependent, peaking at 9 months followed by a gradual decline. GD2 was below the lower limit of quantification in 55% of samples in the > 10 years cohort. Upper bounds of reference intervals were 15.5 nM in 0–6 month cohort, 35.1 nM in 6–12 month cohort, 24.9 nM in 12–36 month cohort, 18.4 in 3–10 year cohort and 10.4 nM in > 10 year cohort. ConclusionsAge-dependent reference intervals were defined for circulating GD2 in children. GD2 concentration was highest in the 6–12 month age cohort, which is below the age of most children with high-risk neuroblastoma. The peak GD2 concentration at 9 months may reflect neurodevelopmental events in the brain.

Effect of fatty acid composition of vegetable oils on crystallization and gelation kinetics of oleogels based on natural wax

This study aimed to understand the effect of fatty acid composition and viscosity of vegetable oils on network formation mechanism and physical properties of oleogels. To this purpose, 12 oleogels were prepared, by choosing 6 seed oils and two waxes, at a fixed oleogelator concentration (6%). The modified Avrami model correctly describes the crystallization profile (R2 > 0.98) and the oil type did not affect the Avrami index that ranged from 1.00 to 1.43. Independently from oleogelator, rice and hemp seed oils followed a 3-D network formation mechanism, while almond oil a 2-D mechanism. The strength and yield stress of carnauba wax oleogels increased with increasing saturated fatty acid amount, while in beeswax-based oleogels a more interconnected structure was associated with the length of the saturated fatty acid chain. Thus, the oleogels formation mechanism was closely related to the chemical composition of the solvent, even in highly monounsaturated or polyunsaturated oils.

Immobilized Fe3O4-Polydopamine-Thermomyces lanuginosus Lipase-Catalyzed Acylation of Flavonoid Glycosides and Their Analogs: An Improved Insight Into Enzymic Substrate Recognition.

The conversion of flavonoid glycosides and their analogs to their lipophilic ester derivatives was developed by nanobiocatalysts from immobilizing Thermomyces lanuginosus lipase (TLL) on polydopamine-functionalized magnetic Fe3O4 nanoparticles (Fe3O4-PDA-TLL). The behavior investigation revealed that Fe3O4-PDA-TLL exhibits a preference for long chain length fatty acids (i.e., C10 to C14) with higher reaction rates of 12.6–13.9 mM/h. Regarding the substrate specificity, Fe3O4-PDA-TLL showed good substrate spectrum and favorably functionalized the primary OH groups, suggesting that the steric hindrances impeded the secondary or phenolic hydroxyl groups of substrates into the bonding site of the active region of TLL to afford the product.

Synthesis and Physicochemical Properties of Low Viscosity 2‐Ethylhexyl Alkyl Ethers Made from Palm‐Based Esters as Potential Biolubricant

AbstractA series of 2‐ethylhexyl alkyl ethers (EHAE) are synthesized from palm‐based esters via a one‐step reaction under mild reaction conditions for potential usage as biolubricant. In this work, 2‐ethylhexyl esters with varying fatty acid chain lengths are reacted with 1,1,3,3‐tetramethyldisiloxane (TMDS), catalyzed by indium bromide (InBr3) at 40 °C to afford EHAE with lauryl, palmityl, stearyl, and oleyl alkyl chain with 55–68% isolated yield. These compounds are characterized using Fourier‐transform infrared (FTIR) and NMR spectroscopic methods and are evaluated for their viscosity, thermal, cold‐flow, oxidative, and anti‐wear properties. The synthesized EHAEs demonstrate low viscosity (1.65–2.55 cSt at 100 °C) with excellent viscosity indices (130–182). These EHAEs show comparable wear scar diameter (0.6–1.0 mm) in comparison with commercial mineral oil base stock (group I SN150) in the four‐ball wear test. Thermal‐oxidative investigation of the EHAE reveals that the thermal degradation temperatures are in the range of 200–250 °C and oxidation onset temperatures are between 165 and 184 °C. Among the EHAEs, 2‐ethylhexyl lauryl ether with the shortest alkyl chain has the lowest pour point of −27 °C. The physicochemical properties of synthesized EHAEs indicate that they are potential as biolubricant base stocks.Practical Applications: The EHAEs produced from this work exhibit promising physicochemical and lubricity properties, which offer great potential to be used as lubricant base stock especially for internal engine oil application.

Transformation of Cyanobacterial Biomolecules by Iron Oxides During Flash Pyrolysis: Implications for Mars Life-Detection Missions.

Answering the question of whether life ever existed on Mars is a key goal of both NASA's and ESA's imminent Mars rover missions. The obfuscatory effects of oxidizing salts, such as perchlorates and sulfates, on organic matter during thermal decomposition analysis techniques are well established. Less well studied are the transformative effects of iron oxides and (oxy)hydroxides, which are present in great abundances in the martian regolith. We examined the products of flash pyrolysis-gas chromatography-mass spectrometry (a technique analogous to the thermal techniques employed by past, current, and future landed Mars missions) which form when the cyanobacteria Arthrospira platensis are heated in the presence of a variety of Mars-relevant iron-bearing minerals. We found that iron oxides/(oxy)hydroxides have transformative effects on the pyrolytic products of cyanobacterial biomolecules. Both the abundance and variety of molecular species detected were decreased as iron substrates transformed biomolecules, by both oxidative and reductive processes, into lower fidelity alkanes, aromatic and aryl-bonded hydrocarbons. Despite the loss of fidelity, a suite that contains mid-length alkanes and polyaromatic hydrocarbons and/or aryl-bonded molecules in iron-rich samples subjected to pyrolysis may allude to the transformation of cyanobacterially derived mid-long chain length fatty acids (particularly unsaturated fatty acids) originally present in the sample. Hematite was found to be the iron oxide with the lowest transformation potential, and because this iron oxide has a high affinity for codeposition of organic matter and preservation over geological timescales, sampling at Mars should target sediments/strata that have undergone a diagenetic history encouraging the dehydration, dihydroxylation, and oxidation of more reactive iron-bearing phases to hematite by looking for (mineralogical) evidence of the activity of oxidizing, acidic/neutral, and either hot or long-lived fluids.

Depth- and temperature-specific fatty acid adaptations in ctenophores from extreme habitats.

ABSTRACTAnimals are known to regulate the composition of their cell membranes to maintain key biophysical properties in response to changes in temperature. For deep-sea marine organisms, high hydrostatic pressure represents an additional, yet much more poorly understood, perturbant of cell membrane structure. Previous studies in fish and marine microbes have reported correlations with temperature and depth of membrane-fluidizing lipid components, such as polyunsaturated fatty acids. Because little has been done to isolate the separate effects of temperature and pressure on the lipid pool, it is still not understood whether these two environmental factors elicit independent or overlapping biochemical adaptive responses. Here, we use the taxonomic and habitat diversity of the phylum Ctenophora to test whether distinct low-temperature and high-pressure signatures can be detected in fatty acid profiles. We measured the fatty acid composition of 105 individual ctenophores, representing 21 species, from deep and shallow Arctic, temperate, and tropical sampling locales (sea surface temperature, −2° to 28°C). In tropical and temperate regions, remotely operated submersibles (ROVs) enabled sampling down to 4000 m. We found that among specimens with body temperatures 7.5°C or colder, depth predicted fatty acid unsaturation levels. In contrast, in the upper 200 m of the water column, temperature predicted fatty acid chain lengths. Taken together, our findings suggest that lipid metabolism may be specialized with respect to multiple physical variables in diverse marine environments. Largely distinct modes of adaptation to depth and cold imply that polar marine invertebrates may not find a ready refugium from climate change in the deep.

Medium-Chain Triglyceride Oil and Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Trials

BackgroundDietary saturated fat raises total cholesterol and LDL cholesterol levels. It is unclear whether these effects differ by the fatty acid chain lengths of saturated fats; particularly, it is unclear whether medium-chain fatty acids increase lipid levels. ObjectivesWe conducted a systematic review to determine the effects of medium-chain triglyceride (MCT) oil, consisting almost exclusively of medium-chain fatty acids (6:0–10:0), on blood lipids. MethodsWe searched Medline and Embase through March 2020 for randomized trials with a minimum 2-week intervention period that compared MCT oil with another fat or oil. Outcomes were total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. Included studies were restricted to adults above 18 years of age. Studies conducted in populations receiving enteral or parenteral nutrition were excluded. Data were pooled using a random-effects meta-analysis. ResultsSeven articles were included in the meta-analysis; LDL cholesterol and HDL cholesterol were reported in 6 studies. MCT oil intake did not affect total cholesterol (0.04 mmol/L; 95% CI, −0.11 to 0.20; I2 = 33.6%), LDL cholesterol (0.02 mmol/L; 95% CI, −0.13 to 0.17; I2 = 28.7%), or HDL cholesterol (−0.01 mmol/L; 95% CI, −0.10 to 0.09; I2 = 74.1%) levels, but did increase triglycerides (0.14 mmol/L; 95% CI, 0.01–0.27; I2 = 42.8%). Subgroup analyses showed that the effects of MCT oil on total cholesterol and LDL cholesterol differed based on the fatty acid profile of the control oil (Pinteraction = 0.003 and 0.008, respectively), with MCT oil increasing total cholesterol and LDL cholesterol when compared to a comparator consisting predominantly of unsaturated fatty acids, and with some evidence for reductions when compared to longer-chain SFAs. ConclusionsMCT oil does not affect total cholesterol, LDL cholesterol, or HDL cholesterol levels, but does cause a small increase in triglycerides.

Controlling the Orientation and Viscoelasticity of Materials-Binding Peptides on Hexagonal Boron Nitride Using Fatty Acids.

The adsorption of materials-binding peptides to technologically relevant 2D nanosheets of h-BN could be transformative for both property modulation and materials applications. To enhance binding, integration of non-natural functionalities into the biomolecule could prove to be important. However, very little is understood regarding the impact of these biomolecular structural alterations on the binding, which could influence the affinity and surface-adsorbed structures. Here, the effect of fatty acid incorporation site and carbon chain length is investigated using the BP7 peptide, previously identified with affinity for h-BN. The peptide was modified at either the N- or C-terminus with a fatty acid chain length of 6-12 carbons long. The binding affinity and bio-overlayer viscoelasticity are quantified using quartz crystal microbalance analysis. While fatty acid conjugation did not substantially affect the affinity of the resultant biomolecules, it did alter the viscoelasticity of the biomolecular overlayer on the h-BN surface based upon the carbon chain length and incorporation site. Molecular dynamics simulations demonstrate interplay between enthalpic and entropic effects in modifying the overlayer viscoelasticity. The simulations predict that C-terminal conjugation promotes the enhancement of upright adsorbed states, compared with the N-terminal case, with this effect most pronounced for the 10-carbon chain.

Discovery and Characterization of Novel Antagonists of the Proinflammatory Orphan Receptor GPR84.

GPR84 is a poorly characterized, nominally orphan, proinflammatory G protein-coupled receptor that can be activated by medium chain length fatty acids. It is attracting considerable interest as a potential therapeutic target for antagonist ligands in both inflammatory bowel diseases and idiopathic pulmonary fibrosis. Successful screening of more than 300 000 compounds from a small molecule library followed by detailed analysis of some 50 drug-like hits identified 3-((5,6-bis(4-methoxyphenyl)-1,2,4-triazin-3-yl)methyl)-1H-indole as a high affinity and highly selective competitive antagonist of human GPR84. Tritiation of a di-iodinated form of the core structure produced [3H]3-((5,6-diphenyl-1,2,4-triazin-3-yl)methyl)-1H-indole, which allowed effective measurement of receptor levels in both transfected cell lines and lipopolysaccharide-treated THP-1 monocyte/macrophage cells. Although this compound series lacks significant affinity at mouse GPR84, homology modeling and molecular dynamics simulations provided a potential rationale for this difference, and alteration of two residues in mouse GPR84 to the equivalent amino acids in the human orthologue, predicted to open the antagonist binding pocket, validated this model. Sequence alignment of other species orthologues further predicted binding of the compounds as high affinity antagonists at macaque, pig, and dog GPR84 but not at the rat orthologue, and pharmacological experiments confirmed these predictions. These studies provide a new class of GPR84 antagonists that display species selectivity defined via receptor modeling and mutagenesis.

Expression, purification, properties, and substrate specificity analysis of Aspergillus niger GZUF36 lipase in Escherichia coli

The extracellular Aspergillus niger GZUF36 lipase (EXANL1) has broad applicability such as synthesis of functional lipids. The wild-type strain is unstable, and the culture time is long. Studies on the selectivity of substrates for EXANL1 are not available. Therefore, this study aimed to express, purify, characterize and analyze the substrate specificity of EAXNL1. The results showed that EXANL1 was stable in the presence of 40 % (v/v) dimethyl sulfoxide, glycerol, toluene, and n-hexane. The relative activity was 104 %, 88 %, 81 %, and 76 %. The residual enzyme activity of EXANL1 was more than 85 % in surfactants with a low concentration. EXANL1 exhibited a high conversion rate (79 %) for p-nitrophenyl palmitate. The molecular docking of p-nitrophenyl palmitate into the active site of EXANL1 indicated that the preference for this fatty acid chain length might be due to the formation of hydrogen bonds. The distance between the carbonyl carbon atom of p-nitrophenyl palmitate and the nucleophilic oxygen atom of serine 162 was 2.91 Å. Both experiments revealed that EXANL1 exhibited higher specificity for p-nitrophenyl palmitate. These results indicated that EXANL1 could be a promising tool in organic synthesis and detergent industry. The molecular docking provided a basis for the explanation on the substrate selectivity of EXANL1.

Integrated lipidomic and transcriptomic analysis reveals clarithromycin-induced alteration of glycerophospholipid metabolism in the cerebral cortex of mice.

Clarithromycin (CLA) has been widely used in the treatment of bacterial infection. Research reveals the adverse effects on the central nervous system among patients receiving CLA treatment; whereas, a relevant underlying mechanism remains considerably unclear. According to our research, an integrated lipidomic and transcriptomic analysis was applied to explore the effect of CLA on neurobehavior. CLA treatment caused anxiety-like behaviors dose-dependently during open field as well as elevated plus maze trials on mice. Transcriptomes and LC/MS-MS-based metabolomes were adopted for investigating how CLA affected lipidomic profiling as well as metabolic pathway of the cerebral cortex. CLA exposure greatly disturbed glycerophospholipid metabolism and the carbon chain length of fatty acids. By using whole transcriptome sequencing, we found that CLA significantly downregulated the mRNA expression of CEPT1 and CHPT1, two key enzymes involved in the synthesis of glycerophospholipids, supporting the findings from the lipidomic profiling. Also, CLA causes changes in neuronal morphology and function in vitro, which support the existing findings concerning neurobehavior in vivo. We speculate that altered glycerophospholipid metabolism may be involved in the neurobehavioral effect of CLA. Our findings contribute to understanding the mechanisms of CLA-induced adverse effects on the central nervous system. 1. Clarithromycin treatment caused anxiety-like behavior with dose-dependent response both in the open field and elevated plus maze test in mice; 2. Clarithromycin exposing predominately disturbed the metabolism of glycerophospholipids in the cerebral cortex of mice; 3. Clarithromycin application remarkably attenuated CEPT1 and CHPT1 gene expression, which participate in the last step in the synthesis of glycerophospholipids; 4. The altered glycerophospholipid metabolomics may be involved in the abnormal neurobehavior caused by clarithromycin.

Molecular-dynamics-simulation-guided membrane engineering allows the increase of membrane fatty acid chain length in Saccharomyces cerevisiae

The use of lignocellulosic-based fermentation media will be a necessary part of the transition to a circular bio-economy. These media contain many inhibitors to microbial growth, including acetic acid. Under industrially relevant conditions, acetic acid enters the cell predominantly through passive diffusion across the plasma membrane. The lipid composition of the membrane determines the rate of uptake of acetic acid, and thicker, more rigid membranes impede passive diffusion. We hypothesized that the elongation of glycerophospholipid fatty acids would lead to thicker and more rigid membranes, reducing the influx of acetic acid. Molecular dynamics simulations were used to predict the changes in membrane properties. Heterologous expression of Arabidopsis thaliana genes fatty acid elongase 1 (FAE1) and glycerol-3-phosphate acyltransferase 5 (GPAT5) increased the average fatty acid chain length. However, this did not lead to a reduction in the net uptake rate of acetic acid. Despite successful strain engineering, the net uptake rate of acetic acid did not decrease. We suggest that changes in the relative abundance of certain membrane lipid headgroups could mitigate the effect of longer fatty acid chains, resulting in a higher net uptake rate of acetic acid.

Aliphatic fatty diamide as renewable phase change materials for thermal energy storage

Aliphatic diamides derived from vegetable oils have been shown to significantly extend both the phase transition temperatures and melting enthalpy of phase change materials (PCMs) for thermal energy storage (TES) applications. Relationships between molecular structure and thermal functionality of aliphatic fatty diamides were established in this work through the study of twelve (12) synthesized symmetrical aliphatic diamides CH3(CH2)m-2CONH(CH2)nHNOC(CH2)m-2CH3 of series m-n-m (fatty acids chain length, m = 12, 14, or 16 and diamine, n = 2, 4, 8 and 10). This study extended the understanding derived from previous studies of nine (9) other aliphatic diamide molecules. The diamides were assessed in terms of crystal structure, thermal stability, thermal transition behavior and possible kinetic effects using XRD, TGA and DSC. This facilitated an investigation of the role structural factors play in phase change characteristics: (1) the aliphatic chain, which facilitates orientation, (2) the balance between the amide interaction through hydrogen bonding and the intra amide steric repulsions and (3) the molecular conformation which drive the entropy of phase change. The study clarified the nature of the competition between dispersion forces, hydrogen bonding, entropic and mass effects in aliphatic fatty diamide PCMs and established molecular structure – thermal function correlations which can assist in intelligent design of superior aliphatic fatty amide molecules for TES applications.

Lipid profiling in chilled coral larvae

Coral reefs are disappearing worldwide as a result of several harmful human activities. The establishment of cryobanks can secure a future for these ecosystems. To design effective cryopreservation protocols, basic proprieties such as chilling tolerance and lipid content must be assessed. In the present study, we investigated chilling sensitivity and the effect of chilling exposure on the lipid content and composition of larvae belonging to 2 common Indo-Pacific corals: Seriatopora caliendrum and Pocillopora verrucosa. The viability of coral larvae incubated with 0.5, 1, and 2 M ethylene glycol (EG), propylene glycol (PG), dimethyl sulfoxide (Me2SO), methanol, or glycerol and kept at 5 °C for different time periods was documented. In addition, we investigated the content of cholesterol, triacylglycerol (TAG), wax ester (WE), sterol ester (SE), lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and several fatty acid (FA) classes in coral propagules incubated with 1 M PG or EG and kept at 5 °C for 6 h. Moreover, we examined seasonal changes in the aforementioned lipid classes in coral larvae. S. caliendrum incubated with 0.5 M PG or Me2SO and chilled for 2 h exhibited a viability rate of 11 ± 11%, whereas P. verrucosa exhibited a viability rate of 22 ± 14% after being chilled for 4 h. Furthermore, the results indicated that chilling exposure did not affect the content of any investigated lipid class in either species. The higher concentration of SE in P. verrucosa compared to S. caliendrum larvae may have contributed to the different cryotolerance displayed by the 2 larval species. A year-round lipid analysis of both coral larvae species revealed trends of homeoviscous adaptation and seasonal enhancement of lipid fluxes from symbionts to the host. During winter, the cholesterol/phospholipid ratio significantly increased, and P. verrucosa larvae exhibited an averagely decrease in FA chain lengths. During spring and summer, intracellular lipid content in the form of TAGs and WEs significantly increased in both species, and the average content of Symbiodiniaceae-derived FAs increased in P. verrucosa larvae. We concluded that the low cryotolerance displayed by S. caliendrum and P. verrucosa larvae is attributable to their chilling-sensitive membrane lipid profile and the high intracellular lipid content provided by their endosymbionts.

Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on chain elongation.

Reportedly, decreases in fatty acid (FA) chain length of ceramide (CER) are associated with interferon-γ (IFN-γ), which shows increased expression in psoriasis. However, the underlying mechanism of this association remains unclear. Therefore, in this study, we aimed to clarify this association between FA chain length of CER, IFN-γ, and the major transcriptional factors involving psoriasis. CER profiling according to FA chain length and class was performed in murine epidermis (n=10 BALB/c mice topically treated with imiquimod, n=10 controls) and human stratum corneum (SC) (n=12 psoriasis, n=11 controls). The expression of lipid synthetic enzymes, including elongases (ELOVLs), in murine epidermis was also measured using RT-PCR. Furthermore, the association of IFN-γ with various enzymes and transcription factors involved in the generation of long-chain CERs was also investigated using in vitro keratinocyte. A significant decrease in the percentage of long-chain CERs was observed in psoriasis-like murine epidermis and human psoriatic SC. Additionally, the expression levels of ELOVL1, ELOVL4, and ceramide synthase3 (CerS3) were significantly decreased in psoriasis-like murine epidermis and IFN-γ-treated keratinocyte. There was also a significant decrease in the expression of transcriptional factors, including peroxisome proliferator-activated receptor (PPAR), in IFN-γ treated keratinocyte. Thus, it could be suggested that IFN-γ may regulate ELOVL and CerS levels by down-regulating the transcriptional factors. Additionally, given the possible involvement of PPARs or liver X receptor agonist in the CER elongation process, they may serve as potential therapeutic agents for lengthening the CER FAs in psoriasis.

Sulfatides are endogenous ligands for the TLR4–MD-2 complex

Many endogenous molecules, mostly proteins, purportedly activate the Toll-like receptor 4 (TLR4)-myeloid differentiation factor-2 (MD-2) complex, the innate immune receptor for lipopolysaccharide (LPS) derived from gram-negative bacteria. However, there is no structural evidence supporting direct TLR4-MD-2 activation by endogenous ligands. Sulfatides (3-O-sulfogalactosylceramides) are natural, abundant sulfated glycolipids that have variously been shown to initiate or suppress inflammatory responses. We show here that short fatty acid (FA) chain sulfatides directly activate mouse TLR4-MD-2 independent of CD14, trigger MyD88- and TRIF-dependent signaling, and stimulate tumor necrosis factor α (TNFα) and type I interferon (IFN) production in mouse macrophages. In contrast to the agonist activity toward the mouse receptor, the tested sulfatides antagonize TLR4-MD-2 activation by LPS in human macrophage-like cells. The agonistic and antagonistic activities of sulfatides require the presence of the sulfate group and are inversely related to the FA chain length. The crystal structure of mouse TLR4-MD-2 in complex with C16-sulfatide revealed that three C16-sulfatide molecules bound to the MD-2 hydrophobic pocket and induced an active dimer conformation of the receptor complex similar to that induced by LPS or lipid A. The three C16-sulfatide molecules partially mimicked the detailed interactions of lipid A to achieve receptor activation. Our results suggest that sulfatides may mediate sterile inflammation or suppress LPS-stimulated inflammation, and that additional endogenous negatively charged lipids with up to six lipid chains of limited length might also bind to TLR4-MD-2 and activate or inhibit this complex.

Effect of Carbon Chain Length, Ionic Strength, and pH on the In Vitro Release Kinetics of Cationic Drugs from Fatty-Acid-Loaded Contact Lenses.

This paper explores the use of fatty acids in silicone hydrogel contact lenses for extending the release duration of cationic drugs. Drug release kinetics was dependent on the carbon chain length of the fatty acid loaded in the lens, with 12-, 14- and 18-carbon chain length fatty acids increasing the uptake and the release duration of ketotifen fumarate (KTF) and tetracaine hydrochloride (THCL). Drug release kinetics from oleic acid-loaded lenses was evaluated in phosphate buffer saline (PBS) at different ionic strengths (I = 167, 500, 1665 mM); the release duration of KTF and THCL was decreased with increasing ionic strength of the release medium. Furthermore, the release of KTF and THCL in deionized water did not show a burst and was significantly slower compared to that in PBS. The release kinetics of KTF and THCL was significantly faster when the pH of the release medium was decreased from 7.4 towards 5.5 because of the decrease in the relative amounts of oleate anions in the lens mostly populated at the polymer–pore interfaces. The use of boundary charges at the polymer–pore interfaces of a contact lens to enhance drug partition and extend its release is further confirmed by loading cationic phytosphingosine in contact lenses to attract an anionic drug.

Effect of feed restriction on fatty acid profile, body composition and selected blood parameters of intensive reared pike (Esox lucius)

This study investigated the effects of a six-week starvation period on the fatty acid profile, body composition and blood parameters of intensively reared pike (Esox lucius). 150 pike were stocked in an experimental recirculating aquaculture system (RAS) and feed was completely withdrawn. Body composition, fatty acid composition and blood parameters (serum protein, albumin, triacylglycerol, cholesterol concentration and Lactate dehidrigenase and alkaline phosphatase activity) were measured and somatic indices were calculated. A significant decline in bodyweight, crude fat content and somatic indices was accompanied by a significant decrease of blood triacylglycerol content. The relative proportion of saturated fatty acids in the fillet decreased, while polyunsaturated fatty acids increased. There was also a significant increase in the average chain length and unsaturation index of fatty acids found in the fillet flesh.

A mutant T1 lipase homology modeling, and its molecular docking and molecular dynamics simulation with fatty acids

A thermostable T1 lipase from Geobacillus zalihae exhibits broad substrate specificity and good potential application in fats and oils. However, structural insight into the enzyme against substrates is poorly understood at the molecular level. Herein, the study aimed to examine interactions between a mutant T1 lipase (Mut-T1 lipase) and selected fatty acids (caprylic, myristic, stearic, oleic, linoleic and linolenic acids) by performing molecular docking and molecular dynamics (MD) simulation. The structure of Mut-T1 lipase obtained by homology modeling was reliable for molecular docking and MD simulation. Molecular docking revealed that Mut-T1 lipase showed low binding affinity for caprylic acid (−4.97 kcal/mol) compared to the other fatty acids (−5.65 to −6.88 kcal/mol). However, the conformation of Mut-T1 lipase-caprylic acid complex was comparably stable during the simulation, in terms of less root-mean square fluctuation. Besides, solvent accessible surface area value of Mut-T1 lipase-fatty acid complexes decreased with increasing chain length of fatty acid. van der Waals interactions were requisite in maintaining complex stability during the binding process. This work provides structural insight into interactions between the lipase and the fatty acids, which will facilitate design and applications of new mutants of T1 lipase in modifying fats and oils.

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.