Hydroxy Fatty Acids Research Articles

Metabolome classification of olive by-products from different oil presses providing insights into its potential health benefits and valorization as analyzed via multiplex MS-based techniques coupled to chemometrics.

The Olive (Olea europaea L.) is one of the most popular edible oil-producing fruits, consumed worldwide for its myriad nutritional and health benefits. Olive oil production generates huge quantities of by-products from the fruit, which are considered environmental hazards. Recently, more and more efforts have been made to valorize olive by-products as a source of low-cost, value-added food applications. The main objective of this study was to globally assess the metabolome of olive fruit by-products, including olive mill wastewater, olive pomace, and olive seeds from fruits from two areas, Siwa and Anshas, Egypt. Gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography with mass spectrometry (UPLC-MS) were used for profiling primary and secondary metabolites in olive by-products. Also, multivariate data analyses were used to assess variations between olive by-product samples. A total of 103 primary metabolites and 105 secondary metabolites were identified by GC-MS and UPLC-MS, respectively. Fatty acids amounted to a major class in the olive by-products at 53-91%, with oleic acid dominating, especially in the pomace of Siwa. Mill wastewater was discriminated from other by-products by the presence of phenolics mainly tyrosol, hydroxyl tyrosol, and α-tocopherol as analyzed by UPLC-MS indicating their potential antioxidant activity. Pomace and seeds were rich in fatty acids/esters and hydroxy fatty acids and not readily distinguishable from each other. The current work discusses the metabolome profile of olive waste products for valorization purposes. Pomace and seeds were enriched in fatty acids/esters, though not readily distinguishable from each other.

Gender-based heterogeneity of FAHFAs in trained runners.

Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in a cross-sectional study of recreationally trained runners. Here we report the influences of body composition and gender on static FAHFA abundances in circulation. We compared the association between circulating FAHFA concentrations and body composition, determined by dual x-ray absorptiometry, in female recreational runners who were lean (BMI < 25 kg/m2, n = 6), to those who were overweight (BMI ≥ 25 kg/m2, n = 7). To characterize the effect of gender we also compared circulating FAHFAs in lean male recreational runners (n = 8) to recreationally trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but strikingly, within the lean cohort, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass, while the overweight group showed a significantly attenuated relationship. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.

Plasma lipidome differences in patients with and without significant carotid plaque

BackgroundAtherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events. AimWe studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque. MethodsThis study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques. ResultsThe lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification. ConclusionsPlasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.

Molecular Mechanism for Regioselectivity of P450-BM3 Monooxygenase Towards Stearic Acid Hydroxylation

Hydroxy stearic acid is an important raw material for the synthesis of biobased materials, and the hydroxylation at different positions showed different properties. With the catalysis of P450-BM3 monooxygenase, (ω - 1)-Hydroxy stearic acid was generated, which is a precursor of macrocyclic musk. Experimental results have shown that the L188Q mutant can increase the yield of (ω - 1)-Hydroxy stearic acid by more than three times, but the reason and underlying molecular mechanism are still unclear. In this study, molecular dynamics (MD) simulations were conducted to study the structural characteristics of the P450-BM3 wild type and its three mutants (F87V, L188Q, and F87V-L188Q) in combination with stearic acid. The MD simulation results showed significant changes in the interactions between the three mutants and the carboxyl- and terminal-end of stearic acid. The results of the Molecular mechanics-Poisson-Boltzmann surface area (MMPBSA) binding free energies indicated that the L188Q mutant showed the most stable binding with the stearic acid. Finally, the H-abstraction free energy barriers of L188Q and wild type systems were calculated to study the regioselectivity, and the results indicated that the L188Q mutant shown a significant advantage in the hydroxylation of stearic acid at the ω - 1 position. Our research results not only explain molecular mechanism for regioselectivity of P450-BM3 towards stearic acid hydroxylation, but also provide some useful ideas for the synthesis of biobased materials from hydroxy fatty acids.

Paneth Cell-Specific TRPV6 Channel Plays a Crucial Role in Alcohol-Associated Dysbiosis of Gut Microbiota and Tissue Injury at the Gut-Liver Axis

Introduction: Endotoxemia plays an essential role in alcohol-associated tissue injury. Two factors contributing to endotoxemia are gut microbiota dysbiosis and epithelial barrier dysfunction. Previous studies indicated that TRPV6 channel-mediated Ca2+ influx plays a crucial role in alcohol-induced epithelial tight junction (TJ) disruption, mucosal barrier dysfunction, and endotoxemia. Trpv6 knockout mice were resistant to alcohol-induced intestinal barrier dysfunction and modulated microbiota dysbiosis, raising the question of how TRPV6 regulates microbiota composition. In this study, we investigated the role of Paneth cell-specific TRPV6 in alcohol-induced microbiota dysbiosis and barrier dysfunction. Methods: Adult Trpv6fl/fl (WT) and Trpv6fl/fl-Defa6Cre (KO; Paneth cell-specific TRPV6 knockout) mice were fed a Lieber-DiCarli liquid diet with EtOH (0% 2d, 1% 2d, 2% 2d, 4% 1wk, 5% 1wk, &amp; 6% 1wk). Control groups were pair-fed an isocaloric EtOH-free diet. Intestinal permeability was measured by vascular-to-luminal flux of FITC-inulin in vivo, and mucosal inflammation was assessed by RT-PCR for cytokines/chemokines. Plasma lipopolysaccharide (LPS) was measured to evaluate endotoxemia. Gut microbiota was analyzed by 16S rRNA sequencing of colonic flushing. Lipidome in colonic flushing was analyzed using nontargeted liquid chromatography-mass spectrometry. Microbiome and lipidome data were processed by bioinformatic analyses. Results and conclusion: Data show that colon length was reduced, and colonic mucosal permeability in vivo was elevated by EtOH in WT mice. The increase in mucosal permeability was associated with increased plasma LPS levels. EtOH feeding elevated the expression of IL-6, IL-1β, and TNFα in the colon. EtOH-induced changes in colon length, mucosal permeability, cytokine expression, and plasma LPS were absent in KO mice. 16S rRNA sequencing data indicated that the microbiota composition in KO mice differed from that of WT mice. The relative abundance of Prevotellaceae, Xanthomonadaceae, and Streptococaceae were higher, and Psuedomonadaceae and Verrucomicrobiaceae abundance were lower in KO mice compared to WT mice. EtOH-induced increase in the abundance of Norcardiaceae and Psuedomonadaceae was low or absent in KO mice. EtOH increased Rhodococcus, Odoribacter, and Pseudomonas abundance at the genus level in WT but not KO mice. On the other hand, Clostridium, Turicibacter, and Helicobacter abundance were increased by EtOH in KO but not WT mice. Lipidomic analysis of colonic flushing showed that phospholipid contents were higher in KO mice than WT mice, irrespective of sex and treatments. A cluster of sphingolipids was dramatically high in KO female mice, which was reduced by EtOH feeding. Short-chain fatty acid esters of hydroxy fatty acids (AAHFA 3:0/24:0;O) were elevated by EtOH in male WT mice but not in female WT and male or female KO mice. In conclusion, these data indicate that Paneth cell-specific deletion of TRPV6 attenuates alcohol-induced changes in gut microbiota, colonic luminal lipids, mucosal barrier function, and endotoxemia in mice. NIH/NIAAA, RO1-AA029270; Veterans Administration IO1-BX003014. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The gut lactic acid bacteria metabolite, 10-oxo-cis-6,trans-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling.

Various gut bacteria, including Lactobacillus plantarum, possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC), a γ-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with γKetoC significantly suppressed proliferation of CD4+ T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c+ cells isolated from the spleen. γKetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further in vitro experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of γKetoC on DCs. We also found that γKetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of γKetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in Nrf2-/- BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and Nrf2+/- mice with colitis. In contrast, the pathology of colitis was deteriorated in Nrf2-/- mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in γKetoC-mediated anti-inflammatory responses.

Alteration of epidermal lipid composition as a result of deficiency in the magnesium transporter Nipal4

Lipids in the stratum corneum play an important role in the formation of the skin permeability barrier. The causative gene for congenital ichthyosis, NIPAL4, encodes a Mg2+ transporter and is involved in increases in intracellular Mg2+ concentrations that depend on keratinocyte differentiation. However, the role of this increased Mg2+ concentration in skin barrier formation and its effect on the lipid composition of the stratum corneum has remained largely unknown. Therefore, in the present study, we performed a detailed analysis of epidermal lipids in Nipal4 KO mice via TLC and MS. Compared with WT mice, the Nipal4 KO mice showed compositional changes in many ceramide classes (including decreases in ω-O-acylceramides and increases in ω-hydroxy ceramides), together with increases in ω-hydroxy glucosylceramides, triglycerides, and free fatty acids and decreases in ω-O-acyl hydroxy fatty acids containing a linoleic acid. We also found increases in unusual ω-O-acylceramides containing oleic acid or palmitic acid in the KO mice. However, there was little change in levels of cholesterol or protein-bound ceramides. The TLC analysis showed that some unidentified lipids were increased, and the MS analysis showed that these were special ceramides called 1-O-acylceramides. These results suggest that elevated Mg2+ concentrations in differentiated keratinocytes affect the production of various lipids, resulting in the lipid composition necessary for skin barrier formation.

Sustainable production of sophorolipid biosurfactants using renewable cellulose‐derived feedstocks

AbstractGlycolipids produced and secreted by oleaginous yeasts are renewable compounds with important physico‐chemical properties, and multiple biological and industrial applications. The large‐scale production of these compounds has been limited by high production costs and low yields. The sophorolipid‐producing yeast Pseudohyphozyma bogoriensis may possess the ability to grow in fermentation systems using carbon substrates deriving from inexpensive lignocellulosic biomass, while simultaneously secreting high value biomaterials. In this study, comparative analyses between different cellulose‐derived carbon sources including glucose, cellobiose, and sodium carboxymethyl cellulose confirmed the ability of P. bogoriensis to grow and accumulate glycolipids using these substrates. On a dry weight basis, the highest yields of about 4% (wt/wt) glycolipids were obtained when cellobiose was supplemented at 10 g/L in shake‐flask fermentations. When the unconventional carbon substrate sodium carboxymethyl cellulose was supplemented, cultures exhibited a lower glycolipid yield of 0.3% (wt/wt), but the dry weight was higher compared to other substrates. Analytical analyses using various chromatography methods confirmed the chemical profiles, whereas both monoacetylated and diacetylated sophorolipid forms with 22 carbon long‐chain hydroxy fatty acid were identified in all glycolipid extracts. Surface tension (ST) and critical micelle concentration (CMC) measurements showed that glycolipids produced on cellulose‐derived substrates exhibited similar or even superior physical properties compared with glucose. Furthermore, availability of the yeast genome sequences facilitated the identification of putative genes that may be involved in cellulose hydrolysis (e.g., cellulase‐like). Information on genomic and metabolic pathways is a prerequisite for trait improvement toward increasing the production of high value biomaterials.

Edible insects as a novel source of lecithin: Extraction and lipid characterization of black soldier fly larvae and yellow mealworm

Edible insects with high fat and phosphorus content are a potential novel source of lecithin, however, studies on their minor lipids are limited. In this study, lecithin was extracted from black soldier fly larvae and yellow mealworm. Herein, the effects of lecithin extraction method, matrix and ultrasound pretreatment were explored based on the fatty acid composition and phospholipid profile with soy lecithin as a reference. The use of a wet matrix and ultrasound pretreatment increased the extraction efficiency of total PLs from both insects. Insect lecithin contained a considerable amount of sphingomyelin compared to soy lecithin. In insect lecithin, a total of 47 glycerophospholipid and sphingomyelin molecular species, as well as four molecular species of fatty acyl esters of hydroxy fatty acid, were detected. This study is the first comprehensive investigation of insects as a new source of lecithin with applications in food, cosmetics and in the pharmaceutical industry.

Comparative Lipidomics of Oral Commensal and Opportunistic Bacteria.

The oral cavity contains a vast array of microbes that contribute to the balance between oral health and disease. In addition, oral bacteria can gain access to the circulation and contribute to other diseases and chronic conditions. There are a limited number of publications available regarding the comparative lipidomics of oral bacteria and fungi involved in the construction of oral biofilms, hence our decision to study the lipidomics of representative oral bacteria and a fungus. We performed high-resolution mass spectrometric analyses (<2.0 ppm mass error) of the lipidomes from five Gram-positive commensal bacteria: Streptococcus oralis, Streptococcus intermedius, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus gordonii; five Gram-positive opportunistic bacteria: Streptococcus mutans, Staphylococcus epidermis, Streptococcus acidominimus, Actinomyces viscosus, and Nanosynbacter lyticus; seven Gram-negative opportunistic bacteria: Porphyromonas gingivalis. Prevotella brevis, Proteus vulgaris, Fusobacterium nucleatum, Veillonella parvula, Treponema denticola, and Alkermansia muciniphila; and one fungus: Candida albicans. Our mass spectrometric analytical platform allowed for a detailed evaluation of the many structural modifications made by microbes for the three major lipid scaffolds: glycerol, sphingosine and fatty acyls of hydroxy fatty acids (FAHFAs).

Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates — Harnessing the potential in the construction of materials for skin regeneration processes

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

Properties of soybean oil oleogels produced from sophorolipid‐derived hydroxy fatty acids, methyl esters and hydrogenated Lesquerella seed oil

AbstractSophorolipids (SL) are glycolipids composed of a sophorose head‐group linked to a hydroxy‐fatty acid tail which makes them a potential source of structurally unique biobased hydroxy fatty acids. Furthermore, Lesquerella is a native southwestern plant that has been commercially cultivated as a replacement for castor seed oil due to high seed oil concentrations of 14‐hydroxy‐eicosenoic acid (14‐OH‐C20:1c11). In this study, SL‐derived hydroxy fatty acids and methyl esters containing 15‐hydroxy‐palmitic acid (15‐OH‐C16), 17‐hydroxy‐stearic acid (17‐OH‐C18), 15‐hydroxy‐palmitic acid methyl ester (15‐OH‐C16ME), 17‐hydroxy‐stearic acid methyl ester (17‐OH‐C18ME), and 13‐hydroxy‐behenic acid methyl ester (13OH‐C22ME) were obtained from the SL produced by two yeast strains. In addition, hydrogenated Lesquerella oil (HLO) was made with ~62% 14‐OH‐eicosanoic (C20) acid (14‐OH‐C20). These materials, along with 12‐hydroxy‐stearic acid (12‐OH‐C18) as a standard for comparison were used to make soybean oil oleogels, and their properties determined. The minimum gelation concentration (MGC) of 12‐OH‐C18 was 1% (wt/wt), while the MGC of 15‐OH‐C16 and 17‐OH‐C18 were 5% and 10%, respectively. The MGC for 15‐OH‐C16ME was 5%, but 17‐OH‐C18ME was unable to form a stable gel at concentrations up to 10%. HLO formed a viscous solution rather than an oleogel, but its crystal morphology underwent a large transformation during storage over a 2.5‐month period, after which it was able to form a stable gel. SL‐based hydroxy fatty acids were able to form oleogels in soybean oil and have the potential to be considered as a new source of low‐molecular weight oleogelators as well as biobased hydroxy fatty acids.

Sex-Specific Effect of Ethanol on Colon Content Lipidome in a Mice Model Using Nontargeted LC/MS.

Consumption of alcohol has widespread effects on the human body. The organs that are most significantly impacted are the liver and digestive system. When alcohol is consumed, it is absorbed in the intestines and processed by the liver. However, excessive alcohol use may affect gut epithelial integrity, microbiome composition, and lipid metabolism. Despite past studies investigating the effect of ethanol on hepatic lipid metabolism, the focus on colonic lipid metabolism has not been well explored. In this study, we investigated the sex-specific effect of ethanol on the colonic content lipidome in a mouse model using nontargeted liquid chromatography-mass spectrometry. Comprehensive lipidome analysis of colonic flush samples was performed using ethanol-fed (EF) and pair-fed (PF) mice of each sex. Partial least-squares discriminant analysis revealed that ethanol altered colonic lipid composition largely in male mice compared with female mice. A significant increase in free fatty acids, ceramides, and hexosylceramides and decreased phosphatidylglycerols (PG) was observed in the EF group compared to the PF group in male mice. Phosphatidylethanolamine (PE) levels were increased significantly in the EF group of both sexes compared to the PF group. The volcanic plot shows that PG (O-15:1/15:0) and PE (O-18:2/15:0) are common markers that are increased in both sexes of the EF group. In addition, decreased fatty acid esters of hydroxy fatty acids (FAHFA) were observed specifically in the EF group of female mice. Overall, a significant variation in the mice colonic content lipidome between the EF and PF groups was observed. Target pathways, such as sphingolipid metabolism in males, FAHFA in females, and PE metabolism in both sexes, were suggested. This study provides new insight into the sex-dependent lipid change associated with alcohol-induced gut-microbiota dysfunction and its potential health impacts.

Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα.

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages. Cell-based transcriptional reporter assays show h18:0 selectively activates PPARα. Radiolabeling experiments with bone marrow-derived macrophages show [1-14C]h18:0 is not incorporated into cellular lipids, but is degraded by β-oxidation, and mass spectrometry detected shortened fragments of h18:0 released into the media. The catabolism of h18:0 was >10-fold lower in bone marrow-derived macrophages isolated from Ppara -/- knockout mice, and we recover 74-fold fewer S. aureus cells from the skin infection site of Ppara -/- knockout mice compared to wildtype mice. These data identify PPARα as a target for oleate hydratase-derived hydroxy fatty acids and support the existence of an oleate hydratase-PPARα signaling axis that functions to suppress the innate immune response to S. aureus.

LORE receptor homomerization is required for 3-hydroxydecanoic acid-induced immune signaling and determines the natural variation of immunosensitivity within the Arabidopsis genus.

The S-domain-type receptor-like kinase (SD-RLK) LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) from Arabidopsis thaliana is a pattern recognition receptor that senses medium-chain 3-hydroxy fatty acids, such as 3-hydroxydecanoic acid (3-OH-C10:0), to activate pattern-triggered immunity. Here, we show that LORE homomerization is required to activate 3-OH-C10:0-induced immune signaling. Fluorescence lifetime imaging in Nicotiana benthamiana demonstrates that AtLORE homomerizes via the extracellular and transmembrane domains. Co-expression of AtLORE truncations lacking the intracellular domain exerts a dominant negative effect on AtLORE signaling in both N. benthamiana and A. thaliana, highlighting that homomerization is essential for signaling. Screening for 3-OH-C10:0-induced reactive oxygen species production revealed natural variation within the Arabidopsis genus. Arabidopsis lyrata and Arabidopsis halleri do not respond to 3-OH-C10:0, although both possess a putative LORE ortholog. Both LORE orthologs have defective extracellular domains that bind 3-OH-C10:0 to a similar level as AtLORE, but lack the ability to homomerize. Thus, ligand binding is independent of LORE homomerization. Analysis of AtLORE and AlyrLORE chimera suggests that the loss of AlyrLORE homomerization is caused by several amino acid polymorphisms across the extracellular domain. Our findings shed light on the activation mechanism of LORE and the loss of 3-OH-C10:0 perception within the Arabidopsis genus.

Effect of wet-aging on meat quality and exudate metabolome changes in different beef muscles

The aim of this study was to evaluate meat quality and changes in the meat exudate metabolome of different beef muscles (5 d postmortem, longissimus lumborum and psoas major muscles) during wet-aging (additional 3, 7, 14, 21, and 28 d of aging). Shear force of meat declined significantly (P < 0.001) with aging, meanwhile, increased myofibril fragmentation index, lipid and protein oxidation with aging were observed (P < 0.01). Psoas major (PM) showed significantly higher (P < 0.05) purge loss, centrifugal loss, and cooking loss, as well as higher tenderness and more severe lipid and protein oxidation (P < 0.01) than longissimus lumborum (LL) during aging. Principal component analysis of the metabolomic profiles revealed distinct clusters according to the period of aging and the type of muscle simultaneously. Overabundant amino acids, peptides, oxidized fatty acids, and hydroxy fatty acids were found in long-term aged meat exudates, and forty metabolites were significantly correlated with meat quality characteristics. Fifty-nine metabolites were significantly affected by muscle type. These results demonstrated the potential possibility of evaluating meat quality using meat exudate metabolomics.

The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats.

Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

Metabolomic profiling of pediatric post-tonsillectomy pain: Aproof-of-concept study.

Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain. Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.

Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity-related diseases.

Obesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti-inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure-activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in-depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed.

Distribution of 3-hydroxy fatty acids in South China Sea since the last deglaciation: Applicability of 3-hydroxy fatty acid-based palaeothermometry

3-Hydroxy fatty acids (3-OH-FAs) are biomarkers for Gram-negative bacteria. Recent research has suggested that they could serve as temperature proxies in both terrestrial and marine environments, based on calibrations using modern samples. However, these proxies have been only applied in a speleothem for the Holocene and a short sediment core in the East China Sea for past 58 years, thus more evidence is needed to testify their validity. In this study, we analyzed the distribution of 3-OH-FAs in a sediment core from the northern South China Sea (SCS) spanning the past 19 thousand years (19 ka). We detected 3-OH-FAs, including normal (n-), iso (i-), and anteiso (a-) isomers, in all 56 samples with carbon numbers ranging from 10 to 18. The distribution of 3-OH-FAs in marine sediments differed from that in terrestrial sediments (soil, stalagmite, and lake sediments), with a higher fractional abundance of anteiso-FAs. Two temperature proxies, RANs and RAN13, showed a positive correlation (R2 = 0.5; p < 0.001), with RANs-SST being closer to the actual sea surface temperature (SST). The reconstructed RANs-SST in our core exhibited a typical glacial-Holocene increase of 2–3 °C (20.8 ± 2.7 °C vs. 24.1 ± 1.3 °C). Several abrupt climate events, such as the Younger Dryas, BØlling/AllerØd, and Heinrich Event 1, were also recorded in RANs-SST. Therefore, our study supports the applicability of 3-OH-FA RANs as a temperature proxy for paleoenvironmental reconstructions, at least in the last glacial periods.