Fatty Acid Chain Length Research Articles

The Polyextremophilic Bacterium Clostridium paradoxum Attains Piezophilic Traits by Modulating Its Energy Metabolism and Cell Membrane Composition.

In polyextremophiles, i.e., microorganisms growing preferentially under multiple extremes, synergistic effects may allow growth when application of the same extremes alone would not. High hydrostatic pressure (HP) is rarely considered in studies of polyextremophiles, and its role in potentially enhancing tolerance to other extremes remains unclear. Here, we investigated the HP-temperature response in Clostridium paradoxum, a haloalkaliphilic moderately thermophilic endospore-forming bacterium, in the range of 50 to 70°C and 0.1 to 30 MPa. At ambient pressure, growth limits were extended from the previously reported 63°C to 70°C, defining C. paradoxum as an actual thermophile. Concomitant application of high HP and temperature compared to standard conditions (i.e., ambient pressure and 50°C) remarkably enhanced growth, with an optimum growth rate observed at 22 MPa and 60°C. HP distinctively defined C. paradoxum physiology, as at 22 MPa biomass, production increased by 75% and the release of fermentation products per cell decreased by >50% compared to ambient pressure. This metabolic modulation was apparently linked to an energy-preserving mechanism triggered by HP, involving a shift toward pyruvate as the preferred energy and carbon source. High HPs decreased cell damage, as determined by Syto9 and propidium iodide staining, despite no organic solute being accumulated intracellularly. A distinct reduction in carbon chain length of phospholipid fatty acids (PLFAs) and an increase in the amount of branched-chain PLFAs occurred at high HP. Our results describe a multifaceted, cause-and-effect relationship between HP and cell metabolism, stressing the importance of applying HP to define the boundaries for life under polyextreme conditions.IMPORTANCE Hydrostatic pressure (HP) is a fundamental parameter influencing biochemical reactions and cell physiology; however, it is less frequently applied than other factors, such as pH, temperature, and salinity, when studying polyextremophilic microorganisms. In particular, how HP affects microbial tolerance to other and multiple extremes remains unclear. Here, we show that under polyextreme conditions of high pH and temperature, Clostridium paradoxum demonstrates a moderately piezophilic nature as cultures grow to highest cell densities and most efficiently at a specific combination of temperature and HP. Our results highlight the importance of considering HP when exploring microbial physiology under extreme conditions and thus have implications for defining the limits for microbial life in nature and for optimizing industrial bioprocesses occurring under multiple extremes.

FadR-Based Biosensor-Assisted Screening for Genes Enhancing Fatty Acyl-CoA Pools in Saccharomyces cerevisiae.

Fatty acid-derived compounds have a range of industrial applications, from chemical building blocks to biofuels. Due to the highly dynamic nature of fatty acid metabolism, it is difficult to identify genes modulating fatty acyl-CoA levels using a rational approach. Metabolite biosensors can be used to screen genes from large-scale libraries in vivo in a high throughput manner. Here, a fatty acyl-CoA sensor based on the transcription factor FadR from Escherichia coli was established in Saccharomyces cerevisiae and combined with a gene overexpression library to screen for genes increasing the fatty acyl-CoA pool. Fluorescence-activated cell sorting, followed by data analysis, identified genes enhancing acyl-CoA levels. From these, overexpression of RTC3, GGA2, and LPP1 resulted in about 80% increased fatty alcohol levels. Changes in fatty acid saturation and chain length distribution could also be observed. These results indicate that the use of this acyl-CoA biosensor combined with a gene overexpression library allows for identification of gene targets improving production of fatty acids and derived products.

Experimental investigation of the effect of fatty acids configuration, chain length, branching and degree of unsaturation on biodiesel fuel properties obtained from lauric oils, high-oleic and high-linoleic vegetable oil biomass

A very good understanding of the structure, level, type and physical property relationships of fatty acids in plants oils and their methyl esters (FAMEs) is of utmost importance when selecting vegetable oils for a particular desired biodiesel quality that meets the operating condition requirements of the compression-ignition diesel engine and the climatic dictate of the environment under which the engine is operated. It is on this premise that the degree of influence of fatty acid configuration, chain length, branching and unsaturation on cold flow and critical properties of biodiesel was investigated. The critical properties studied include: saponification and cetane number, iodine value, higher heating values, density, flash point and kinematic viscosity. The feed stock consists of three groups of vegetable oil biomass. The group one is made up of highly saturated, lauric coconut and palm kernel oils while group two consists of high linoleic, soyabean and corn oil biomass with low percentage of mono-unsaturated and high percentage of poly-unsaturated fatty acid. High oleic olive and canola oil constituted the third group of biomass. The triglycerides in these oils were converted to methyl esters by alkali-catalyzed transesterification reaction under standard conditions. The fatty acid methyl esters (FAMEs) compositional analyses of these feed stocks was done by using Agilent, HP 6890 Gas Chromatograph equipped with Flame ionization detector and 6890 Auto Sampler that connects with a controller box (GC-FID). The various biodiesel cold flow behaviour and critical properties under investigation were evaluated by the American society for testing materials (ASTM D6751-07b) and the European union (EN 14214) standard procedures and techniques.Better cold flow behaviour was exhibited by biomass with higher degree of unsaturation, longer chain length, higher degree of branching and with cis configuration. While critical properties showed a lot of variations based on fatty acid profile.

Fatty Acid Biosynthesis: Chain-Length Regulation and Control.

De novo biosynthesis of fatty acids is an iterative process requiring strict regulation of the lengths of the produced fatty acids. In this review, we focus on the factors determining chain lengths in fatty acid biosynthesis. In a nutshell, the process of chain-length regulation can be understood as the output of a chain-elongating C-C bond forming reaction competing with a terminating fatty acid release function. At the end of each cycle in the iterative process, the synthesizing enzymes need to "decide" whether the growing chain is to be elongated through another cycle or released as the "mature" fatty acid. Recent research has shed light on the factors determining fatty acid chain length and has also achieved control over chain length for the production of the technologically interesting short-chain (C4 -C8 ) and medium-chain (C10 -C14 ) fatty acids.

The influence of fatty acid chain length on the chemical, physical and morphological properties of the grafted barley husk for application in biocomposites

Abstract The present study deals with the grafting of barley husk (BH) with lauric acid, palmitic acid and arachidic acid in the presence of redox initiators. The grafting reaction parameters (reaction time, reaction temperature, dimethyl sulphoxide (DMSO) content, fatty acid concentration) were optimized by one variable at a time approach (OVAT) and response surface methodology (RSM) coupled with central composite design (CCD). The crystallinity of BH decreased after grafting of BH with long chain fatty acids. The grafted BH samples showed higher thermal stability as compared to BH and the thermal degradation rate of grafted BH decreased with increase in the chain length of fatty acid. Water contact angle (WCA) of BH was 45° and increased to 140–145° after grafting with lauric acid, palmitic acid and arachidic acid. After grafting, swelling (%) of BH decreased in polar solvents (water, ethanol), however, it increased in dimethyl formaldehyde (DMF). Chemical resistance and hydrophobic transformation of BH improved with an increase in % graft yield as well as with fatty acid chain length.

Saturated Fatty Acids from Dairy Increase Energy Expenditure Following an Acute Meal Challenge (P08-015-19)

ObjectivesEvidence suggests that the amount of fatty acid saturation and chain length affect fatty acid oxidation. Metabolism of unsaturated fatty acids may increase energy expenditure and shorter chain fatty acids may be selectively oxidized more readily. More data are needed to determine the impact of fatty acids, as they exist in dietary fats and oils, upon energy expenditure. We tested differences in energy expenditure after an acute meal challenge prepared with dietary fats and oils with fatty acids of differing chain lengths and saturation. The fats and oils used included olive oil (OO, for oleic acid, 18:1n-9), flaxseed oil (FL, for alpha-linolenic acid, 18:3n-3), sunflower oil (SO, for linoleic acid, 18:2n-6), heavy cream (HC, for saturated fatty acids) and fish oil (FO, for docosahexaenoic acid, 22:6n-3). MethodsHealthy men and women (N = 27; 56% men; age: 26.8 ± 6.8; BMI: 29.1 ± 3.2), participated in a five-way crossover trial with intention to treat analysis. Body composition was assessed prior to the first study visit by dual X-ray absorptiometry. A standard three-day lead-in diet, prescribed for the participants’ energy needs, was consumed prior to testing. Subjects entered the metabolic chamber the evening before testing and were awakened at 6 AM for a resting metabolic rate measurement followed by a four-hour meal challenge. Test days were separated by at least 7 days. A 500 kcal smoothie with 30 g of test fat source was consumed within 15 min of an initial fasting blood draw. Metabolic rate (MR) and oxidation rates for fat, carbohydrate and protein were analyzed with proprietary software (PiLR™; MEI Research, Ltd.) for four hours after the challenge. ResultsMR standardized to fat free mass (FFM) and independent of FFM was greater after HC (1.64 ± 0.24 kcal/min) than FL (1.55 ± 0.26 kcal/min) and OO (1.53 ± 0.24 kcal/min) (P < 0.01) over the 4 hr postprandial period. Over four hours these differences accounted for 21.6 and 26.4 fewer kcal oxidized, respectively. Substrate oxidation rates did not differ between dietary fats. ConclusionsIn contrast to previously reported data, our initial data suggest dairy-derived saturated fatty acids may increase postprandial MR following an acute meal challenge. Funding SourcesThis work was supported by USDA-ARS project 3062-51000-053-00D.

P‐113: Ligand‐Dependent Stabilities and Optical Properties of InP / GaP / ZnS Quantum Dots

InP‐based quantum dot (QDs) with the alkyl chain length of fatty acid as ligand were synthesized via a heating up method and evaluated the stabilities against thermal heating and ultraviolet (UV) irradiation. QDs with myristic acid and palmitic acid were appropriately 50% more stable than the one with stearic acid under the evaluation conditions.

Identification of lipopeptides from Bacillus strain Q11 with ability to inhibit the germination of Penicillium expansum, the etiological agent of postharvest blue mold disease

The genus Bacillus produces secondary metabolites among which stand out compounds of polypeptide nature for their versatility of applications, one of them is the activity against fungal phytopathogens of agricultural importance. In the present work was evaluated the effectiveness of the crude lipopeptide from Bacillus subtilis Q11 against common soil borne pathogens, additionally in vitro and in vivo assays were carried out to determine the ability to inhibit the germination of conidia and reduce the blue mold rot induced by Penicillium expansum in apple (Malus domestica Borkh) fruit. In antagonistic test, the lipopeptide fraction of Q11 was able to limit the mycelial growth of Rhizoctonia solani, Sclerotium rolfsii, Penicillium expansum, Fusarium stilboides, Colletotrichum gleosporides and Botrytis cinerea, showing higher inhibition at higher lipopeptide concentrations (10, 20, and 30 μg disk−1); however, it was ineffective against Pseudomonas syrigae, Xanthomonas campestris, and Clavibacter michiganensis. On the other hand, the conidia of P. expansum after being exposed to a concentration of 800 mg L−1 of lipopeptide for 16 h, showed swelling and germination reduction greater than 90%. In fruit assay with apples inoculated with a droplet of conidia suspension (200 conidia) of P. expansum, the treatment with the lipopeptide fraction reduced rot lesion severity, registering the greatest effects at 80 μg, which reduced the size of the lesion by more than 60%. The analysis by infrared spectroscopy, HPLC and MALDI-TOF established that the crude lipopeptide is a complex formed primarily by iturin-type compounds with fatty acid chain length of C14–C17 and small proportion of compounds of fengycin A and B type that differ in the length of the fatty acid chain. These compounds could be useful in the development of products for biological control of postharvest blue mold disease in apple.

Fatty acid conjugation enhances potency of antisense oligonucleotides in muscle.

Enhancing the functional uptake of antisense oligonucleotide (ASO) in the muscle will be beneficial for developing ASO therapeutics targeting genes expressed in the muscle. We hypothesized that improving albumin binding will facilitate traversal of ASO from the blood compartment to the interstitium of the muscle tissues to enhance ASO functional uptake. We synthesized structurally diverse saturated and unsaturated fatty acid conjugated ASOs with a range of hydrophobicity. The binding affinity of ASO fatty acid conjugates to plasma proteins improved with fatty acid chain length and highest binding affinity was observed with ASO conjugates containing fatty acid chain length from 16 to 22 carbons. The degree of unsaturation or conformation of double bond appears to have no influence on protein binding or activity of ASO fatty acid conjugates. Activity of fatty acid ASO conjugates correlated with the affinity to albumin and the tightest albumin binder exhibited the highest activity improvement in muscle. Palmitic acid conjugation increases ASO plasma Cmax and improved delivery of ASO to interstitial space of mouse muscle. Conjugation of palmitic acid improved potency of DMPK, Cav3, CD36 and Malat-1 ASOs (3- to 7-fold) in mouse muscle. Our approach provides a foundation for developing more effective therapeutic ASOs for muscle disorders.

Distinct fatty acid signatures in infrapatellar fat pad and synovial fluid of patients with osteoarthritis versus rheumatoid arthritis

BackgroundInfrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients.MethodsPairs of IFP and SF samples were collected from the same knees of RA (n = 10) and OA patients (n = 10) undergoing total joint replacement surgery. Control SF samples (n = 6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection.ResultsArthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA.ConclusionsThe observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.

Engineering Saccharomyces cerevisiae cells for production of fatty acid-derived biofuels and chemicals.

The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals, in particular ethanol, a biofuel produced in large quantities. With a need for high-energy-density fuels for jets and heavy trucks, there is, however, much interest in the biobased production of hydrocarbons that can be derived from fatty acids. Fatty acids also serve as precursors to a number of oleochemicals and hence provide interesting platform chemicals. Here, we review the recent strategies applied to metabolic engineering of S. cerevisiae for the production of fatty acid-derived biofuels and for improvement of the titre, rate and yield (TRY). This includes, for instance, redirection of the flux towards fatty acids through engineering of the central carbon metabolism, balancing the redox power and varying the chain length of fatty acids by enzyme engineering. We also discuss the challenges that currently hinder further TRY improvements and the potential solutions in order to meet the requirements for commercial application.

Influence of Phospholipids Structure on the Physicochemical Properties and In Vitro Digestibility of Lactoferrin-Loaded Liposomes

The instability of liposomal delivery system during passaging through the gastrointestinal tract (GIT) stimulates a demand to find a stable liposome. This research studied the implications of different types of phospholipids (different fatty acid chain length and saturation, various head group) on liposomal physiochemical properties and stability in the human GIT. The micropolarity of liposomal membrane increased with the decrease of chain lengths of phospholipids, while the morphology observation revealed that the liposomes formed by different phospholipids showed similar in appearance and shapes. The liposomes formed by C20:0 deformed more severely in simulated gastric fluid, while others exhibited slight changes in the membrane structure. In simulated intestinal fluid, pancreatic lipase and phospholipase A2, synergized with bile salts, damaged the bilayers structure of all liposomes, with the entrapped lactoferrin release and hydrolysis. Although the various phospholipid structures lead to some difference on the physicochemical properties (size and micropolarity), the enzymic influence displayed more significance during in vitro digestion compared to the types of wall materials. Current results could provide valuable information for the development of more stable and reliable food-grade liposomes in the GIT.

The roles of short and long chain fatty acids on physicochemical properties and improved cancer targeting of albumin-based fattigation-platform nanoparticles containing doxorubicin

The aim of this study was to investigate the impact of different chain length fatty acids on physicochemical properties and cancer targeting of fattigation-platform nanoparticles (NPs). Two different types of fatty acids (short chain, 2-hydroxybutyric acid, C4; long chain, oleic acid, C18:1) were successfully conjugated to human serum albumin (HSA) via simple 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling reaction. These conjugates readily formed HSA-C4 and HSA-C18:1 NPs which showed good stability in serum and desirable biocompatibility with normal cell line (HEK293T). Doxorubicin hydrochloride (DOX) was efficiently loaded into NPs by incubation process via electrostatic interaction. The structure, morphology, and texture of DOX-loaded NPs were characterized by Transmission electron microscopy (TEM) equipped with Energy-dispersive X-ray spectroscopy (EDS). The initial burst release of DOX-loaded NPs was controlled by the presence and chain length of fatty acids. In vitro cytotoxicity studies with three cancer cell lines (A549, HT-29, and PANC-1) suggested that fattigation-platform NPs have distinctive cytotoxic effects compared to Doxil®. Confocal microscopy and flow cytometry exhibited that the cellular uptake of DOX-loaded NPs was varied by the different chain lengths of fatty acids. It was evident that the chain length of fatty acids in the fattigation-platform NPs could play a vital role in varying physicochemical properties and cancer cell targeting of NPs.

Biochemical characterization of three new \u03b1-olefin-producing P450 fatty acid decarboxylases with a halophilic property

BackgroundThe CYP152 family member OleTJE from Jeotgalicoccus sp. ATCC 8456 has been well-known to catalyze the unusual one-step decarboxylation of free fatty acids towards the formation of terminal alkenes. Efforts to tune up its decarboxylation activity for better production of biological alkenes have been extensively explored via approaches such as site-directed mutagenesis and electron source engineering, but with limited success. To gain more insights into the decarboxylation mechanism and reaction bifurcation (decarboxylation versus hydroxylation), we turned to an alternative approach to explore the natural CYP152 resources for a better variety of enzyme candidates.ResultsWe biochemically characterized three new P450 fatty acid decarboxylases including OleTJH, OleTSQ and OleTSA, with respect to their substrate specificity, steady-state kinetics, and salt effects. These enzymes all act as an OleTJE-like fatty acid decarboxylase being able to decarboxylate a range of straight-chain saturated fatty acids (C8–C20) to various degrees. Site-directed mutagenesis analysis to the lower activity P450 enzyme OleTSA revealed a number of key amino acid residues within the substrate-binding pocket (T47F, I177L, V319A and L405I) that are important for delicate substrate positioning of different chain-length fatty acids and thus the decarboxylation versus hydroxylation chemoselectivity, in particular for the mid-chain fatty acids (C8–C12). In addition, the three new decarboxylases exhibited optimal catalytic activity and stability at a salt concentration of 0.5 M, and were thus classified as moderate halophilic enzymes.ConclusionThe P450 fatty acid decarboxylases OleTJE, OleTJH, OleTSQ and OleTSA belong to a novel group of moderate halophilic P450 enzymes. OleTJH from Jeotgalicoccus halophilus shows the decarboxylation activity, kinetic parameters, as well as salt tolerance and stability that are comparable to OleTJE. Site-directed mutagenesis of several key amino acid residues near substrate-binding pocket provides important guidance for further engineering of these P450 fatty acid decarboxylases that hold promising application potential for production of α-olefin biohydrocarbons.

Preparation of Renewable Epoxy-Amine Resins With Tunable Thermo-Mechanical Properties, Wettability and Degradation Abilities From Lignocellulose- and Plant Oils-Derived Components.

One-hundred percent renewable triphenol—GTF—(glycerol trihydroferulate) and novel bisphenols—GDFx–(glycerol dihydroferulate) were prepared from lignocellulose-derived ferulic acid and vegetal oil components (fatty acids and glycerol) using highly selective lipase-catalyzed transesterifications. Estrogenic activity tests revealed no endocrine disruption for GDFx bisphenols. Triethyl-benzyl-ammonium chloride (TEBAC) mediated glycidylation of all bis/triphenols, afforded innocuous bio-based epoxy precursors GDFxEPO and GTF-EPO. GDFxEPO were then cured with conventional and renewable diamines, and some of them in presence of GTF-EPO. Thermo-mechanical analyses (TGA, DSC, and DMA) and degradation studies in acidic aqueous solutions of the resulting epoxy-amine resins showed excellent thermal stabilities (Td5% = 282–310°C), glass transition temperatures (Tg) ranging from 3 to 62°C, tunable tan α, and tunable degradability, respectively. It has been shown that the thermo-mechanical properties, wettability, and degradability of these epoxy-amine resins, can be finely tailored by judiciously selecting the diamine nature, the GTF-EPO content, and the fatty acid chain length.

A hydrolase with esterase activity expressed from a fosmid gene bank prepared from DNA of a North West Himalayan glacier frozen soil sample.

Screening of 20,000 clones of a fosmid gene bank, constructed from DNA extracted from North West Himalaya (NWH) glacier soil sample, using functional approach identified 10 esterase/lipase-producing clones. Of these, a clone designated pFG43 with an insert size of 45kb which produced the highest concentration of enzyme (467.43U/mg) was sequenced. Clone pFG43 contained 61 open reading frames (ORF) and of these an ORF of 1155bp designated ME-003, was found to be closely related to a hydrolase from Acidobacteria sps (77% sequence identity and E value = 1e-164) and subsequently identified as a putative cocaine esterase. ORF ME-003 was amplified and sub-cloned using a TA vector system into E. coli (DH5α). The purified recombinant enzyme with a molecular weight of 43kDa had optimal activity at 40°C, pH 6 and the highest activity with shorter chain fatty acids than with higher chain length fatty acids. There is insignificant effect of inhibitors on the enzyme activity of ME-003, except PMSF which completely inhibited its activity. ME-003 activity was also inhibited in the presence of copper oxide but remained stable in presence of other metal ions. The enzyme activity was also inhibited in the presence of organic solvents; however, in the presence of 10% isopropanol, 12% of enzymatic activity was retained. Among various detergents, SDS completely inhibited enzymatic activity. The recombinant enzyme also shows enantio-specific activity against the racemic drug intermediates/precursors and exhibited 90% ee against racemic 1-phenyl ethanol and fluoxetine.

Saturated Fat Intake Is Associated with Lung Function in Individuals with Airflow Obstruction: Results from NHANES 2007⁻2012.

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007–2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV1), FEV1, forced vital capacity (FVC), FEV1/FVC ratio, percent predicted FEV1 and percent predicted FVC. Multivariable regression models in the general population as well as those with spirometry-defined airflow obstruction were used to assess the relationship between lung function measurements and dietary SFA intake after adjustment for confounders. 11,180 eligible participants were included in this study. Univariate analysis revealed a statistically significant positive association between total SFA intake and lung function outcomes; however, these relationships were attenuated after adjustment for covariates. A secondary analysis of individuals with spirometry-defined airflow obstruction (FEV1/FVC < 0.7) revealed that a lower intake of SFA was associated with reduced FEV1 (β = −126.4, p = 0.04 for quartile 1 vs. quartile 4), FVC (β = −165.8. p = 0.01 for quartile 1 vs. quartile 4), and percent predicted FVC (β = −3.3. p = 0.04 for quartile 1 vs. quartile 4), after adjustment for relevant confounders. No associations were observed for the FEV1/FVC ratio and percent predicted FEV1. It is possible that characteristics such as food source and fatty acid chain length may influence associations between saturated fatty acid intake and health outcomes.

Effects of chain length of saturated fatty acids on Aβ generation in SH-SY5Y cells

Many studies have shown that saturated fat diet increases the risk of AD. Recently saturated very long chain fatty acids (VLCFAs) have been found be accumulated in AD patients. The variety of saturated fatty acids are found in the diets and human bodies. However, it is not clear which one or more fatty acids are involved in AD pathogenesis. This study investigated the effects of three saturated fatty acids with different carbon chain length (C16:0, C20:0, and C26:0) on amyloid precursor protein (APP) processing and amyloid-β peptide (Aβ) generation. Here, SH-SY5Y cells were treated with vehicle, C16:0, C20:0, and C26:0 (10 μmol/L, 24 h). Compared to the vehicle, C16:0 did not cause any significantly change in APP processing and Aβ generation. C20:0 and C26:0 increased Aβ levels and the expressions of APP, β- and γ-secretase and decreased the expression of α-secretase, and C26:0 had the strongest effects among three fatty acids. Moreover, C20:0 and C26:0 significantly increased reactive oxygen species (ROS), and C16:0 had no such effect. These data indicate that saturated fatty acids with different carbon chain length (C16:0, C20:0 and C26:0) have different effects on the process of Aβ generation, and fatty acids with longer chain (C20:0 and C26:0) have more potential to promote Aβ production and an underlying mechanism of fatty acids action may be related to the elevated oxidative stress. This work supports saturated very long chain fatty acids may play a potential role in the pathogenesis of AD.

Structural Changes of Starch-Lipid Complexes during Postprocessing and Their Effect on In Vitro Enzymatic Digestibility.

The effects of cooking and storage on the structure and in vitro enzymatic digestibility of complexes formed between fatty acids and debranched high-amylose starch (DHA7-FA) were investigated for the first time. Cooking greatly decreased the crystallinities of DHA7-lauric acid (LA) and DHA7-myristic acid (MA) complexes but had little effect on the crystallinities of DHA7-palmitic acid (PA) and DHA7-stearic acid (SA) complexes. Cooking increased the enthalpy-change (Δ H) values and short-range molecular orders of DHA7-FA complexes. Cooking decreased the in vitro enzymatic digestibility of DHA7-FA complexes, with the extent of the effect decreasing with increasing fatty acid chain length. Holding the samples at 4 °C for 24 h after cooking did not greatly affect the long- and short-range molecular orders nor the in vitro enzymatic digestibility of DHA7-FA complexes. From this study, we conclude that cooking disrupted the long-range crystalline structures of DHA7-LA and DHA7-MA complexes but enhanced the short-range molecular orders of all of the DHA7-FA complexes. The latter effect accounted mainly for the reduced in vitro enzymatic digestibility of DHA7-FA complexes.

Design, screening and biological evaluation of novel fatty acid chain-modified oxyntomodulin-based derivatives with prolonged glucose-lowering ability and potent anti-obesity effects.

Recently, oxyntomodulin (OXM) has emerged as a treatment option for type 2 diabetes mellitus and obesity. In order to develop more promising novel OXM derivatives combining glycemic effects of glucagon-like peptide-1 (GLP-1) and lipolytic properties of glucagon, six 12-mer GLP-1 receptor agonists (PP01-PP06) were screened using a phage display method and then fused to OXM (3-37) to generate hybrid OXM derivatives (PP07-PP12). PP11, as a selected starting point, was further site-specifically modified with three lengths of fatty acid chains to provide long-acting conjugates PP13-PP24, among which PP18 was found not only to retain almost the entire balanced activation potency of PP11 in GLP-1/glucagon receptors but also to enhance plasma stability and prolong hypoglycemic activity. PP18 was further confirmed as an insulin secretagogue and glycemic agent in gene knockout mice. The protracted antidiabetic effects and in vivo half-life of PP18 were further proved by hypoglycemic efficacies in diet-induced obesity (DIO) mice and pharmacokinetics tests in Sprague Dawley (SD) rats, respectively. Nevertheless, administration of PP18 once per day normalized food intake, body weight, blood biochemical indexes, insulin resistance and islet function of DIO mice. These preclinical results suggested that PP18, as a novel OXM-based dual GLP-1 and glucagon receptor agonist, may serve as a novel therapeutic approach to treat T2DM and obesity.