Fatty Acid Oxidation Products Research Articles

Analysis of glycerol bound ω-oxo-fatty acids as ω-dioxane-FAME-derivatives

ω-oxo-fatty acids, also known as aldehydic fatty acids, are major products of fatty acid oxidation and pose potential health risks. When bound to glycerol, ω-oxo-fatty acids (core aldehydes) can be ingested with food. Challenges in GC–MS quantification include the absence of an appropriate internal standard. Additionally, substantial analyte losses during sample preparation, caused by the high volatility of short-chain compounds, alter their pattern based on molecular weight. In this study, among various tested derivatization methods, the formation of ω-dioxane derivatives demonstrated improved recovery rates after three evaporation cycles. For methyl 7-oxo-heptanoate, recovery increased from 43 % to 88 %, while recovery rates for different chain lengths and a novel synthesized internal standard improved from a range of 43 %–76 % to 87 %–92 %. Additionally, ω-dioxane derivatives displayed favorable GC–MS behavior, enabling clear identification and increased sensitivity. Finally, ω-oxo-fatty acids were quantified as their ω-dioxane-derivatives in thermally treated sunflower and rapeseed oil.

Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver

The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (p < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.

Odor-Active Compounds in Flexible Polyurethane Materials

Flexible polyurethane (PU) materials find extensive use in upholstery, mattresses, and automobiles, yet the molecular background of their odor is still inadequately understood. To address this gap, we aimed at identifying major odorants in fifteen samples representing eight common types of flexible PU materials. The volatiles isolated from the samples were subjected to activity-guided screening via gas chromatography-olfactometry. Structures were assigned by comparing odor, retention data, and mass spectra to those of authentic reference compounds. This approach led to the identification of 50 odorants, 39 of which had not previously been described in PU. The odorants belonged to a wide range of compound classes, including tertiary amines, fatty acid oxidation products, short-chain aldehydes, trioxocanes, pyrazines, aromatic hydrocarbons and heterocycles, chlorinated compounds, phenol derivatives, fragrance compounds, and nitriles. For some odorants, further insights were gained into their origins and release behavior. For example, the odorous 1,4-dimethylpiperazine had been used as a catalyst, and propanal was shown to be not only a PU odorant but also the precursor of an odor-active trioxocane. Additionally, the quantitation of acetaldehyde and propanal suggested their continuous regeneration from the samples. While the sources of other compounds still have to be clarified, the data obtained in this study could pave the way for odor reduction strategies in the production of PU materials, ultimately resulting in an improved odor and consumer experience.

Effect of deodorization conditions on fatty acid profile, oxidation products, and lipid-derived free radicals of soybean oil

Oxidative stability is a key quality characteristic of edible oils, and the oil’s antioxidant capacity decreases during the deodorization stage. This study explores the changes in radical formation, molecular structure, oxidative characteristics, fatty acids, and main bioactive compounds in soybean oil during deodorization. The lag phase decreased, whereas the total amount of spins of free radicals increased as the deodorization time increased from 90 to 150 min. The total amount of spins and percentage of alkyl radicals varied dramatically under different times and temperatures (220 ∼ 260 ℃). Results showed that identifying and quantifying the formed radicals can provide useful information for monitoring and controlling oil oxidation in vegetable oil refining systems. Therefore, to control early oxidation events, maximize refined oil product yield, and reduce energy consumption in the refining plant, the priority should be to minimize temperature during the oil refining process and then shorten the deodorization time.

Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation

Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, levels of fatty acid oxidation (FAO) by-products, intestinal stem cells (ISCs), levels of hypoxia-inducible factor 1 subunit α (HIF-1α) and its downstream genes such as peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1a (CPT1A) were assessed at distinct time intervals following intestinal ischemia with or without the interference of HIF-1α. Our data showed that HPC facilitates the restoration of the intestinal structure and enhances the FAO, by boosting intestinal stem cells. Additionally, HIF-1α, PPARα, and CPT1A mRNA and their protein levels were generally up-regulated in the small intestine of HPC rats as compared to the control group. Our vitro experiment also shows low-oxygen induces highly levels of HIF-1α and its downstream genes, with a concurrent increase in FAO products in IEC-6 cells. Furthermore, the above phenomenon could be reversed by silencing HIF-1α. In conclusion, we hypothesize that HPC can stimulate the activation of intestinal stem cells via HIF-1α/PPARα pathway-mediated FAO, thereby accelerating the healing process post ischemic intestinal injury.

Exerkines, Nutrition, and Systemic Metabolism.

The cornerstones of good health are exercise, proper food, and sound nutrition. Physical exercise should be a lifelong routine, supported by proper food selections to satisfy nutrient requirements based on energy needs, energy management, and variety to achieve optimal metabolism and physiology. The human body is sustained by intermediary and systemic metabolism integrating the physiologic processes for cells, tissues, organs, and systems. Recently, interest in specific metabolites, growth factors, cytokines, and hormones called exerkines has emerged to explain cooperation between nutrient supply organs and the brain during exercise. Exerkines consist of different compounds described as signaling moiety released during and after exercise. Examples of exerkines include oxylipin 12, 13 diHOME, lipid hormone adiponectin, growth factor BDNF, metabolite lactate, reactive oxygen species (ROS), including products of fatty acid oxidation, and cytokines such as interleukin-6. At this point, it is believed that exerkines are immediate, fast, and long-lasting factors resulting from exercise to support body energy needs with an emphasis on the brain. Although exerkines that are directly a product of macronutrient metabolism such as lactate, and result from catabolism is not surprising. Furthermore, other metabolites of macronutrient metabolism seem to be candidate exerkines. The exerkines originate from muscle, adipose, and liver and support brain metabolism, energy, and physiology. The purpose of this review is to integrate the actions of exerkines with respect to metabolism that occurs during exercise and propose other participating factors of exercise and brain physiology. The role of diet and macronutrients that influence metabolism and, consequently, the impact of exercise will be discussed. This review will also describe the evidence for PUFA, their metabolic and physiologic derivatives endocannabinoids, and oxylipins that validate them being exerkines. The intent is to present additional insights to better understand exerkines with respect to systemic metabolism.

Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a morbid disease characterized by significant lung endothelial cell (EC) dysfunction. Prior work has shown that microvascular endothelial cells (MVECs) isolated from animals with experimental PAH and patients with PAH exhibit significant abnormalities in metabolism and calcium signaling. With regards to metabolism, we and others have shown evidence of increased aerobic glycolysis and evidence of increased utilization of alternate fuel sources (such as fatty acids) in PAH EC. In the realm of calcium signaling, our prior work linked increased activity of the transient receptor potential vanilloid-4 (TRPV4) channel to increased proliferation of MVECs isolated from the Sugen/Hypoxia rat model of PAH (SuHx-MVECs). However, the relationship between metabolic shifts and calcium abnormalities was not clear. Specifically, whether shifts in metabolism were responsible for increasing TRPV4 channel activity in SuHx-MVECs was not known. In this study, using human data, serum samples from SuHx rats, and SuHx-MVECs, we describe the consequences of increased MVEC fatty acid oxidation in PAH. In human samples, we observed an increase in long-chain fatty acid levels that was associated with PAH severity. Next, using SuHx rats and SuHx-MVECs, we observed increased intracellular levels of lipids. We also show that increasing intracellular lipid content increases TRPV4 activity, whereas inhibiting fatty acid oxidation normalizes basal calcium levels in SuHx-MVECs. By exploring the fate of fatty acid-derived carbons, we observed that the metabolite linking increased intracellular lipids to TRPV4 activity was β-hydroxybutyrate (BOHB), a product of fatty acid oxidation. Finally, we show that BOHB supplementation alone is sufficient to sensitize the TRPV4 channel in rat and mouse MVECs. Returning to humans, we observe a transpulmonary BOHB gradient in human patients with PAH. Thus, we establish a link between fatty acid oxidation, BOHB production, and TRPV4 activity in MVECs in PAH. These data provide new insight into metabolic regulation of calcium signaling in lung MVECs in PAH.NEW & NOTEWORTHY In this paper, we explore the link between metabolism and intracellular calcium levels in microvascular endothelial cells (MVECs) in pulmonary arterial hypertension (PAH). We show that fatty acid oxidation promotes sensitivity of the transient receptor potential vanilloid-4 (TRPV4) calcium channel in MVECs isolated from a rodent model of PAH.

Evaluation of meat and meat product oxidation and off-flavor formation: Managing oxidative changes

One of the primary issues with processed foods during heat treatment and freezing storage is fat oxidation, which causes significant changes in fats due to their interaction with reactive oxygen species (ROS). This interaction leads to the creation of various aldehydes that have a high affinity for large molecules, such as proteins, leading to the formation of final products of advanced oxidation processes that contribute to food spoilage. Co-oxidation can also result in extensive damage. Another problem affecting the quality and nutritional value of meat products is protein oxidation, which can occur during storage via freezing and thawing or as a result of heat treatment. Heat treatment can cause physical and chemical changes, such as the loss of some essential amino acids and the transformation of certain amino acids into carbonyl compounds via various mechanisms. Protein oxidation is indicated by the accumulation of these carbonyl compounds, and the heat treatment can lead to the denaturation of myoglobin, which is responsible for the brown color of cooked meat and is influenced by several factors. Active protein aggregates can interact with the oxidation products of polyunsaturated fatty acids and with carbohydrate glycation or glycoxidation to produce Maillard products. It is critical to understand the oxidative changes that occur in fats and proteins in food, particularly in meat products, since these components are among the primary constituents of food.

Beyond Autoxidation and Lipoxygenases: Fatty Acid Oxidation Products in Plant Oils.

For decades, research on oxidation of linoleic acid (LA, C18:2 n6) and α-linolenic acid (ALA, C18:3 n3) in plant oils has focused on autoxidatively formed and lipoxygenase-derived 9-hydro(pero)xy- and 13-hydro(pero)xy-LA and -ALA. Here, using a non-targeted approach, we show that other hydroxy fatty acids are more abundant in plant oils. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry analyses unveiled highly abundant peaks in flaxseed and rapeseed oils. Using authentic reference standards, seven of the peaks were identified as 9-, 10-, 12-, 13-, and 15-HODE as well as 9- and 13-HOTrE. Additionally, six peaks were characterized based on the retention time, the exact mass of the [M-H]- ion, and its fragment ions as 16-OH-C18:3, 18-OH-C18:3, three isomers of 12-OH-C18:2, and one of 15-OH-C18:2. 16-OH-C18:3 and 18-OH-C18:3 were tentatively identified as 16-OH-ALA and 18-OH-ALA, respectively, based on autoxidation and terminal hydroxylation of ALA using CYP4F2. Investigation of formation pathways suggests that fatty acid desaturase 3 is involved in the formation of the 12-OH-C18:2 isomers, 15-HODE, and its isomer. The dominantly occurring 12-OH-C18:2 isomer was identified as 12R,S-OH-9Z,15Z-octadecadienoic acid (densipolic acid) based on a synthetic standard. The characterized oxylipins occurred in cold-pressed flaxseed and rapeseed oils at concentrations of up to 0.1 g/100 g and thus about sixfold higher than the well-known 9-hydro(pero)xy- and 13-hydro(pero)xy-LA and -ALA. Concentrations in sunflower oil were lower but increased when oil was pressed from preheated seeds. Overall, this study provides fundamental new information about the occurrence of oxidized fatty acids in plant oils, having the potential to characterize their quality and authenticity.

Effects of Individual Circulating FFAs on Plasma and Hepatic FFA Epoxides, Diols, and Epoxide-Diol Ratios as Indices of Soluble Epoxide Hydrolase Activity.

Oxylipins, oxidation products of unsaturated free fatty acids (FFAs), are involved in various cellular signaling systems. Among these oxylipins, FFA epoxides are associated with beneficial effects in metabolic and cardiovascular health. FFA epoxides are metabolized to diols, which are usually biologically less active, by soluble epoxide hydrolase (sEH). Plasma epoxide-diol ratios have been used as indirect measures of sEH activity. This study was designed to examine the effects of acute elevation of individual plasma FFAs on a variety of oxylipins, particularly epoxides, diols, and their ratios. We tested if FFA epoxide-diol ratios are altered by circulating FFA levels (i.e., substrate availability) independent of sEH activity. Wistar rats received a constant intravenous infusion of olive (70% oleic acid (OA)), safflower seed (72% linoleic acid (LA)), and fish oils (rich in ω-3 FFAs) as emulsions to selectively raise OA, LA, and ω-3 FFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), respectively. As expected, olive, safflower seed, and fish oil infusions selectively raised plasma OA (57%), LA (87%), EPA (70%), and DHA (54%), respectively (p < 0.05 for all). Raising plasma FFAs exerted substrate effects to increase hepatic and plasma epoxide and diol levels. These increases in epoxides and diols occurred to similar extents, resulting in no significant changes in epoxide-diol ratios. These data suggest that epoxide-diol ratios, often used as indices of sEH activity, are not affected by substrate availability or altered plasma FFA levels and that epoxide-diol ratios may be used to compare sEH activity between conditions of different circulating FFA levels.

Oxylipin secretion by human CD3+ T lymphocytes in vitro is modified by the exogenous essential fatty acid ratio and life stage.

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation. A number of PUFAs are precursors to oxylipins, including the essential fatty acids (EFAs) linoleic acid (LA) and α-linolenic acid (ALA). LA and ALA are also substrates for synthesis of longer chain PUFAs. Studies with stable isotopes have shown that the relative amounts of LA and ALA can influence their partitioning by T lymphocytes between conversion to longer chain PUFAs and to oxylipins. It is not known whether the relative availability of EFA substrates influences the overall pattern of oxylipin secretion by human T cells or if this changes across the life stages. To address this, the oxylipin profile was determined in supernatants from resting and mitogen activated human CD3+ T cell cultures incubated in medium containing an EFA ratio of either 5:1 or 8:1 (LA : ALA). Furthermore, oxylipin profiles in supernatants of T cells from three life stages, namely fetal (derived from umbilical cord blood), adults and seniors, treated with the 5:1 EFA ratio were determined. The extracellular oxylipin profiles were affected more by the EFA ratio than mitogen stimulation such that n-3 PUFA-derived oxylipin concentrations were higher with the 5:1 EFA ratio than the 8:1 ratio, possibly due to PUFA precursor competition for lipoxygenases. 47 oxylipin species were measured in all cell culture supernatants. Extracellular oxylipin concentrations were generally higher for fetal T cells than for T cells from adult and senior donors, although the composition of oxylipins was similar across the life stages. The contribution of oxylipins towards an immunological phenotype might be due to the capacity of T cells to synthesize oxylipins rather than the nature of the oxylipins produced.

Harmonization of OF LC‐MS oxylipin analysis to investigate lipid mediator formation and signaling in immune cells

The oxidation products of polyunsaturated fatty acids (PUFA) ‐ oxylipins ‐ are formed via enzymatic conversion by cyclooxygenases, lipoxygenases (LOX) and cytochrome P450 monooxygenases or by autoxidation. Together with multiple PUFA substrates this leads to a large variety of oxylipins, whose physiological functions are ‐ besides those of well‐studied prostaglandins and leukotrienes ‐ little understood. The interplay of several PUFA‐oxidizing enzymes, as in the case of multihydroxylated oxylipins, additionally complicates the investigation of their biosynthesis. Due to regulatory crosstalk and complex interactions of different oxylipin classes during physiological processes, such as inflammation, a study of the whole oxylipin profile rather than individual compounds is necessary. Therefore, in order to understand the functions of these lipid mediators potent and reliable biochemical methods and (molecular) biological models are required, in combination with sensitive and sound preanalytical, analytical and post‐analytical procedures for their investigation.The first part of this thesis investigated the relevance of harmonizing such analytical methods for the quantitative determination of oxylipins in biological samples. Based on the outcome of an international laboratory comparison, comparable and reproducible results were obtained across independent laboratories when these harmonized methods were used for sample preparation and analysis by means of liquid chromatography coupled with tandem mass spectrometry. The examination of the effect of different storage times and temperatures as a parameter of pre‐analytics demonstrated that oxylipin levels in plasma samples are robust to long‐term storage and, furthermore, to minor variations during plasma generation. As accurate quantification of oxylipin concentrations rises and falls with the quality of analytical standards, a strategy for the verification of oxylipin standard concentrations with mass‐ spectrometry and UV spectroscopy based approaches using certified standard compounds was presented.In the second part of the thesis the established methods were applied to study the biosynthesis of oxylipins in immune cells with a special attention to the involved LOX. Stimulation of primary human M2‐like macrophages with the liver X receptor (LXR) agonist T09 led to a massive induction of ALOX15 gene expression and thus, 15‐LOX abundance and activity. Cholesterol derivatives were identified as potent endogenous ligands of LXR yielding increased 15‐LOX abundance and activity. The examination of 5‐LOX induced synthesis of multihydroxylated metabolites through supplementation of neutrophils with 15‐HETE, 18‐ HEPE and 17‐HDHA primary leads to formation of double oxygenated oxylipins. In intact cells 5‐LOX preferred DHA‐derived 17‐HDHA as substrate, whereas upon cell integrity destruction the formation of 15‐HETE derived multihydroxylated oxylipins increased.With the combination of harmonized protocols for sampling and analysis this thesis sets the basis for the reliable quantification of oxylipins. The use of the optimized methodologies allowed to further characterize regulatory pathways of the ARA cascade in human immune cells, contributing to a more thorough understanding of inflammation regulation.

COMPARISON OF DIFFERENT SOLID PHASE MICROEXTRACTION FIBERS IN EXTRACTION OF VOLATILE COMPOUNDS FROM ADIPOSE TISSUE

The volatile compounds (VCs) in headspace of adipose tissues (perirenal, tail, caul) were extracted by solid-phase microextraction (SPME) fiber coated with carboxen/ polydimethylsiloxane (CAR/PDMS) or divinylbenzene/ carboxen/ polydimethylsloxane (DVB/CAR/PDMS). In extraction with CAR/PDMS coating compared to DVB/CAR/PDMS, more VCs were obtained in perirenal (53 versus 41), tail (51 vs 47) and caul (35 vs 33) fats. Increased retention index for aldehydes increased the adsorption on DVB/CAR/PDMS. This fiber also provided a good yield for carboxylic acids. CAR/PDMS fiber could be recommended for VCs from adipose tissues if the goal is to identify aldehydes, especially fatty acid oxidation products and low molecular weight hydrocarbons, as well as greater number of VCs. However, in case of targeting carboxylic acids, esters, and also high molecular weight aldehydes, DVB/CAR/PDMS could be utilized due to its high affinity for mentioned compounds. Furthermore, the optimum extraction time should be studied to determine the time for VCs to reach equilibrium.

Sex-Specific Response of the Brain Free Oxylipin Profile to Soluble Epoxide Hydrolase Inhibition.

Oxylipins are the oxidation products of polyunsaturated fatty acids and have been implicated in neurodegenerative disorders, including dementia. Soluble epoxide hydrolase (sEH) converts epoxy-fatty acids to their corresponding diols, is found in the brain, and its inhibition is a treatment target for dementia. In this study, male and female C57Bl/6J mice were treated with an sEH inhibitor (sEHI), trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks to comprehensively study the effect of sEH inhibition on the brain oxylipin profile, and modulation by sex. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure the profile of 53 free oxylipins in the brain. More oxylipins were modified by the inhibitor in males than in females (19 versus 3, respectively) and favored a more neuroprotective profile. Most were downstream of lipoxygenase and cytochrome p450 in males, and cyclooxygenase and lipoxygenase in females. The inhibitor-associated oxylipin changes were unrelated to serum insulin, glucose, cholesterol, or female estrous cycle. The inhibitor affected behavior and cognitive function as measured by open field and Y-maze tests in males, but not females. These findings are novel and important to our understanding of sexual dimorphism in the brain's response to sEHI and may help inform sex-specific treatment targets.

The Influence of Antioxidant Plant Extracts on the Oxidation of O/W Emulsions

The demand for natural cosmetics has steadily increased in recent years. However, challenges occur especially in quality preservation regarding oxidative spoilage of natural cosmetic products, as the use of synthetic preservatives and antioxidants is limited. Therefore, it is important to find nature-based ingredients to ensure shelf life in natural cosmetic formulations. As a result, potential is seen in the use of plant-based antioxidant extracts. The aim of this work was to determine the suitability of the method combination by measuring the antioxidant activity, oxygen concentration, and volatile oxidation products via gas chromatography (hexanal) for the characterization of the influence of some plant extracts on the oxidative stability of natural cosmetic emulsions. Plant extracts of Riesling (Vitis vinifera) pomace, apple (Malus domestica) pomace, coffee (Coffea arabica) grounds, cocoa (Theobroma cacao) husk, and coffee (Coffea arabica) powder extract were incorporated in stable O/W emulsion formulations, while an emulsion without extract functioned as blank. Afterwards, the emulsions were subjected to 3-month accelerated storage tests with and without light exposure. Their oxygen uptake was investigated, and headspace gas chromatography measurements were performed to detect the fatty acid oxidation products formed during oxidative processes in the samples. The results showed that all emulsion samples under light exposure had a higher oxygen uptake and an increase in the characteristic fatty acid oxidation products compared with those stored under light exclusion. However, differences in oxygen uptake under light exposure were observed depending on the plant extract. Therefore, for O/W emulsions, the daily oxygen consumption rate correlated exponentially with the antioxidant activity, and the hexanal concentration correlated linearly with the daily oxygen consumption rate.

Retrograde regulation of mitochondrial fission and epithelial to mesenchymal transition in hepatocellular carcinoma by GCN5L1.

Metabolic reprogram is crucial to support cancer cell growth and movement as well as determine cell fate. Mitochondrial protein acetylation regulates mitochondrial metabolism, which is relevant to cancer cell migration and invasion. The functional role of mitochondrial protein acetylation on cancer cell migration remains unclear. General control of amino acid synthesis 5 like-1(GCN5L1), as the regulator of mitochondrial protein acetylation, functions on metabolic reprogramming in mouse livers. In this study, we find that GCN5L1 expression is significantly decreased in metastatic HCC tissues. Loss of GCN5L1 promotes reactive oxygen species (ROS) generation through enhanced fatty acid oxidation (FAO), followed by activation of cellular ERK and DRP1 to promote mitochondrial fission and epithelia to mesenchymal transition (EMT) to boost cell migration. Moreover, palmitate and carnitine-stimulated FAO promotes mitochondrial fission and EMT gene expression to activate HCC cell migration. On the other hand, increased cellular acetyl-CoA level, the product of FAO, enhances HCC cell migration. Taken together, our finding uncovers the metastasis suppressor role as well as the underlying mechanism of GCN5L1 in HCC and also provides evidence of FAO retrograde control of HCC metastasis.

Effect of Hop β-Acids Extract Supplementation on the Volatile Compound Profile of Roasted Chicken Meat

The increased interest in greener sources of antioxidants has spurred the research on natural alternatives to enhance poultry production. This study aimed to investigate the effects of natural antioxidant extracts’ (hop β-acids extract) diet supplementation at different concentrations (0, 30, 60, and 120 mg kg−1) on the volatile compound profile of roasted chicken meat. A method based on headspace solid-phase micro-extraction coupled to gas chromatography-mass spectrometry (HS-SPME-GC-MS) was optimized by response surface design to extract the volatile compounds. The optimum extraction conditions were 80 °C and 45 min. A total of 95 volatile compounds were identified in roasted chicken meat, especially aldehydes, alkanes, alcohols, esters, and pyrazines. Principal component analysis (PCA) separated the samples as a function of β-acid supplementation, indicating that increased levels of supplementation lead to distinct volatile profiles in roasted chicken meat. Aldehydes such as octanal and hexanal (8.94% and 17.63%, respectively, for 30 mg kg−1 treatment) played an important role in distinguishing the samples. Those compounds are the main oxidation products of unsaturated fatty acids, which are possibly protected by the antioxidant properties of hop β-acid extracts. Some other compounds with odoriferous importance detected for this level of supplementation were: 2,6-dimethyl pyrazine (5.12%), 2-pentylfuran (2.94%), and 1-octen-3-ol (1.88%). This study significantly contributes to the elucidation of the impact of hops β-acids supplementation in the chicken meat aroma profile, opening new venues for its potential application.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A2 is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D2 metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E2 leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.

Identification, quantitation and sensory elucidation of off-taste compounds in wheat bran

Through sensory guided isolation and targeted as well as untargeted analytical techniques such as LC-MS/MS, LC-TOF-MS and 1D/2D-NMR experiments, as part of the SENSOMICS approach key off-taste compounds could be identified, quantified as well as sensorically characterized in wheat bran isolates. Alkenyl resorcinols, namely (Z)-5-nonadec-12/14-enylresorcinol as well as (Z)-5-heneicos-12/14/16-enylresorcinol could be identified as major bitter compounds in wheat bran for the first time. Furthermore, saturated analogues, alkyl resorcinols, which had previously been described to contribute to off-flavour in wheat bran, along with known off-taste compounds fatty acids as well as fatty acid oxidation products were identified to be key contributors to off-taste as well, exhibiting taste threshold between 12 and 981 µmol/kg.

Plasma Levels of Omega-3 and Omega-6 Derived Oxylipins Are Associated with Fecal Microbiota Composition in Young Adults

Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 ± 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho ≥ 0.415, p ≤ 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho ≥ -0.270, p ≤ 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera (Firmicutes phylum; all rho ≥ -0.263, p ≤ 0.024), as well as Sutterella, Succinivibrio, and Gemmiger genera (Proteobacteria phylum; all rho ≥ -0.263, p ≤ 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus (Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera.