Lysophosphatidylcholine Research Articles

Identifying early predictive and diagnostic biomarkers and exploring metabolic pathways for sepsis after trauma based on an untargeted metabolomics approach

Systemic inflammatory response syndrome (SIRS) and organ dysfunction make it challenging to predict which major trauma patients are at risk of developing sepsis. Additionally, the unclear pathogenesis of sepsis after trauma contributes to its high morbidity and mortality. Identifying early predictive and diagnostic biomarkers, as well as exploring related metabolic pathways, is crucial for improving early prevention, diagnosis, and treatment. This study prospectively analyzed plasma samples from patients with severe trauma collected between March 2022 and November 2023. Trauma patients were divided into two groups based on whether they developed sepsis within two weeks: the TDDS group (trauma patients who did not develop sepsis) and the TDS group (trauma patients who did develop sepsis). Plasma samples from the TDS group were collected at the time of sepsis diagnosis (Sepsis group). Metabolite concentrations were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) through untargeted metabolomics. From the differential metabolites between the TDS and TDDS groups, we identified five significant metabolites (all area under the curve (AUC) ≥ 0.94) as early predictive biomarkers for sepsis after trauma: (1) docosatrienoic acid, (2) 7-alpha-carboxy-17-alpha-carboxyethylandrostan lactone phenyl ester, (3) sphingomyelin (SM) 8:1;2O/26:1, (4) N1-[1-(3-isopropenylphenyl)-1-methylethyl]-3-oxobutanamide, and (5) SM 34:2;2O. Furthermore, five significant metabolites (all AUC ≥ 0.85) were identified as early diagnostic biomarkers from the comparison between the TDS and TDDS groups: (1) lysophosphatidylcholine (LPC) O-22:1, (2) LPC O-22:0, (3) uric acid, (4) LPC O-24:2, and (5) LPC 22:0-SN1. 26 metabolites shared between two comparisons (TDS vs. TDDS and sepsis vs. TDS) were identified. Of which, 19 metabolites belong to lipid metabolism. The top three metabolic pathways related to sepsis after trauma under the impact of severe trauma were: (1) glycerophospholipid metabolism, (2) porphyrin metabolism, and (3) sphingolipid metabolism. The top three metabolic pathways related to sepsis after trauma under the impact of infection were: (1) caffeine metabolism, (2) biosynthesis of unsaturated fatty acids, and (3) steroid hormone biosynthesis. Our study identified early predictive and diagnostic biomarkers and explored metabolic pathways related to sepsis after trauma. These findings provide a foundation for future research on the onset and development of sepsis, facilitating its early prevention, diagnosis, and treatment based on specific metabolites and metabolic pathways.

Providing lysophosphatidylcholine-bound omega-3 fatty acids increased eicosapentaenoic acid, but not docosahexaenoic acid, in the cortex of mice with the apolipoprotein E3 or E4 allele.

Providing lysophosphatidylcholine-bound omega-3 fatty acids increased eicosapentaenoic acid, but not docosahexaenoic acid, in the cortex of mice with the apolipoprotein E3 or E4 allele.

Accurate evaluation of the lipid characteristics and flavor of abdominal muscle resulting from different cooking processes using lipidomics and GC-IMS analysis.

Accurate evaluation of the lipid characteristics and flavor of abdominal muscle resulting from different cooking processes using lipidomics and GC-IMS analysis.

Metabolite profiling and adaptation mechanisms of Aspergillus cristatus under pH stress.

pH is an important environmental factor affecting the survival of fungi, and Aspergillus cristatus, which can grow and reproduce over a wide range of pH, is suitable for studying their adaptation mechanism to pH stress. In this study, A. cristatus was cultured on plates of different initial pH (pH 3.8-8.0), with the results revealing distinct morphologies at pH 3.0-5.0, pH 6.0-7.0 and pH 8.0. Liquid chromatography-mass spectrometry (LC-MS) and multivariate analysis subsequently were used to analyze the changes of substance metabolism of A. cristatus at different pH. LC-MS and multivariate analyses showed that A. cristatus's growth at different pH involved significantly different metabolites. In particular, comparing pH 4.0 vs pH 6.0, pH 6.0 vs pH 8.0 and pH 4.0 vs pH 8.0 revealed a total of 317, 171 and 404 significantly different substances, respectively. Finally, as the pH changed from 4.0 to 6.0 to 8.0, eight changes in the patterns of differential substances were identified. At low pH, A. cristatus accumulated large amounts of energy substances (e.g., adenosine), active antioxidants (e.g., glutathione) and osmo-protective substances (e.g., raffinose). In contrast, at high pH, large amounts of phosphatidylcholine (PC), lysophosphatidyl ethanolamine (LPE), lysophosphatidyl choline (LPC), lysophosphatidyl serine (LPS) related to biofilms were synthesized, alongside antioxidants (e.g., formononetin) and acidic substances. The aforementioned results indicate that A. cristatus adapts to changes in pH by adjusting their metabolite synthesis. Therefore, under unsuitable pH environments, A. cristatus synthesizes specific sets of metabolites that play key roles to cope with the stress.

Ganoderma lucidum spore oil attenuates acute liver injury by modulating lipid metabolism and gut microbiota.

Ganoderma lucidum spore oil attenuates acute liver injury by modulating lipid metabolism and gut microbiota.

Circulatory lipid signature in response to short-term testosterone gel treatment of healthy young females

The impact of testosterone administration on the circulating lipidome in females remains unexplored, despite its relevance to understanding metabolic disorders like polycystic ovary syndrome (PCOS). This study addresses this gap by examining the effects of testosterone gel on the plasma lipidome of healthy women over three menstrual cycles. A cohort of 14 women aged 22–37 years with regular cycles was analyzed, with plasma samples collected at baseline, during peak testosterone levels (D45), and post-treatment (D59, D80). Testosterone gel treatment lasted 28 days, administered between day 29 and day 57 of the study. Using a deep-targeted lipidomic approach, 597 lipids were quantified to provide a detailed profile of the lipidome and capture subtle changes in lipid species and their associations with testosterone fluctuations. Extensive profiling revealed a significant decrease in 17 lipid species, especially ether- and ester-linked lysophosphatidylcholines (LPC), at peak testosterone. These lipid reductions were strongly negatively correlated with free and total testosterone, as well as dihydrotestosterone (DHT), and positively correlated with SHBG levels. Notably, intra-individual lipid variability was consistently lower than inter-individual variability, indicating a highly personalized lipidome regulation. Despite testosterone-induced changes, overall plasma lipidome alterations were minimal, suggesting mechanisms that maintain lipid homeostasis. This study highlights the complex interplay between testosterone and lipid metabolism in women. The minimal overall lipidome changes and high inter-individual variability point to the need for further research to assess the clinical relevance of these findings, particularly in hyperandrogenic conditions like PCOS.Clinical Trial Registration number: This study was registered on https://www.isrctn.com/ (ISRCTN10122130) on 09/01/2019.

Exploration of Lipid Mediators for Therapeutic Monitoring of Pancreatic Cancer Patients.

Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood-based protein markers are sometimes useless for evaluating the real-time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators. Lipidomic analysis was conducted by liquid chromatography-mass spectrometry (LC-MS) using serum exosome-derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time-point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal-treated PDAC patient cohort. Nontarget LC-MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time-point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non-relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (p=0.04) and was linked to progressive-free survival (PFS) (p=0.04). PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.

Development of Tricyclic 4,5-Dihydro-3H-pyrrolo[2,3-c]quinolin-4-ones as Potent Autotaxin Inhibitors for Pulmonary Fibrosis Treatment In Vivo.

Autotaxin (ATX) has been recognized as an attractive target due to its hyperactivity in hydrolyzing lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) throughout the initiation and progression of fibrotic diseases. Herein, a hydrophilic amide linker and sp3-rich bicyclic 4,5,6,7-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one scaffold were employed to modify the lead compound PAT-409, followed by benzene ring fusion to generate novel tricyclic 4,5-dihydro-3H-pyrrolo[2,3-c]quinolin-4-one ATX inhibitors. Among them, the pyridine-2-carboxylic derivatives 45 and 46 demonstrated subnanomolar ATX inhibition (IC50 < 1 nM), with a favorable heart safety profile (hERG > 30 μM) and minimal fibroblast toxicity. Significantly, in bleomycin-induced pulmonary fibrosis mouse models, both compounds markedly improved respiratory function and reduced fibrotic lesions. Mechanistic studies revealed that 45 suppressed the TGF-β/Smad signaling pathway, downregulating α-smooth muscle actin (α-SMA) and extracellular matrix components (ECM). Overall, the identification of 45 and 46 for pulmonary fibrosis therapy provides a featured tricyclic scaffold for further development of novel ATX inhibitors.

Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson’s disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation

In Parkinson’s Disease (PD), elevated serum lysophosphatidylcholine (LPC) levels correlate with disease progression. However, the mechanisms by which abnormal LPC elevation contributes to PD-related neurotoxicity remain poorly understood. This study aims to investigate the pathogenic role of LPC in dopaminergic neuronal damage and elucidates its underlying mechanisms. Our results showed LPC induces α-synuclein aggregation, exacerbating cognitive dysfunction. LPC activates Cleaved-Caspase3 via the orphan receptor GPR35-ERK signaling pathway, inhibits GRASP65 expression, and disrupts the polarized structure of the Golgi apparatus. This disruption impairs glycosylation and function of glucocerebrosidase (GCase), preventing its transport to lysosomes and leading to glucosylceramide (GlcCer) accumulation, a scaffold for α-synuclein aggregation. LPC also disrupts the autophagolysosomal pathway and lysosomal acidification, exacerbating toxic α-synuclein accumulation. Restoring GCase glycosylation, limiting GlcCer synthesis, or blocking ERK signaling mitigates these effects. This study highlights LPC’s role in promoting α-synuclein aggregation and autophagolysosomal dysfunction, advancing our understanding of PD pathology.

Plasma lipidomic alterations during pathogenic SIV infection with and without antiretroviral therapy.

Lipid profiles change in human immunodeficiency virus (HIV) infection and correlate with inflammation. Lipidomic alterations are impacted by multiple non-HIV-related behavioral risk factors; thus, use of animal models in which these behavioral factors are controlled may inform on the specific lipid changes induced by simian immunodeficiency virus (SIV) infection and/or antiretroviral therapy (ART). Using ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy, we assessed and compared (ANOVA) longitudinal lipid changes in naïve and ART-treated SIV-infected pigtailed macaques (PTMs). Key parameters of infection (IL-6, TNFa, D-dimer, CRP and CD4+ T cell counts) were correlated (Spearman) with lipid concentrations at critical time points of infection and treatment. Sphingomyelins (SM) and lactosylceramides (LCER) increased during acute infection, returning to baseline during chronic infection; Hexosylceramides (HCER) increased throughout infection, being normalized with prolonged ART; Phosphatidylinositols (PI) and lysophosphatidylcholines (LPC) decreased with SIV infection and did not return to normal with ART; Phosphatidylethanolamines (PE), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC) were unchanged by SIV infection, yet significantly decreased throughout ART. Specific lipid species (SLS) were also substantially modified by SIV and/or ART in most lipid classes. In conclusion, using a metabolically controlled model, we identified specific lipidomics signatures of SIV infection and/or ART, some of which were similar to people living with HIV (PWH). Many SLS were identical to those involved in development of organ dysfunctions encountered in virally suppressed individuals. Lipid changes also correlated with markers of disease progression, inflammation and coagulation. Our data suggest that lipidomic profile alterations contribute to residual systemic inflammation and comorbidities seen in HIV/SIV infections and therefore may be used as biomarkers of SIV/HIV comorbidities. Further exploration into the benefits of interventions targeting dyslipidemia is needed for the prevention HIV-related comorbidities.

Maternal omega-3 polyunsaturated fatty acids improved levels of DHA-enriched phosphatidylethanolamines and enriched lipid clustering in the neuronal membranes of C57BL/6 mice fetal brains during gestation.

Maternal omega-3 polyunsaturated fatty acids improved levels of DHA-enriched phosphatidylethanolamines and enriched lipid clustering in the neuronal membranes of C57BL/6 mice fetal brains during gestation.

Identification of age-related metabolomic signatures in vascular tissues.

Identification of age-related metabolomic signatures in vascular tissues.

Untargeted metabolomics combined with lipidomics revealed the effects of myocardial infarction and exercise rehabilitation on blood circulation metabolism of patients based on liquid chromatography-mass spectrometry.

Untargeted metabolomics combined with lipidomics revealed the effects of myocardial infarction and exercise rehabilitation on blood circulation metabolism of patients based on liquid chromatography-mass spectrometry.

EXPLORING THE ROLE OF MICROBIAL PHOSPHOLIPIDS IN VISCERAL HYPERSENSITIVITY AND ALTERED EMOTIONAL BEHAVIOUR INDUCED BY INFLAMMATORY BOWEL DISEASE (IBD)-ASSOCIATED MICROBIOTA

Abstract IBD is characterized by relapsing episodes of inflammation in the gastrointestinal tract. Abdominal pain is common in IBD and often persists without overt inflammation. Moreover, patients with IBD are more likely to develop anxiety and depression, further impairing their quality of life. Recently, gut microbiota emerged as a tentative pathophysiological factor in pain and mood disorders. However, little is known about the specific mechanisms by which microbiota modulate pain and mental health in IBD. We hypothesized that bacteria contribute to visceral hypersensitivity and behavioural abnormalities in IBD via modulation of bioactive phospholipids, focusing on lysophosphatidylcholine (LPC) and its metabolite lysophosphatidic acid (LPA), which were previously linked to chronic pain, anxiety and depression. To address our hypothesis, fecal samples from healthy controls (HC n=15) and IBD patients (n=35; Crohn’s Disease (CD) n=18, Ulcerative Colitis (UC) n=17) were collected to assess the levels of LPC and LPA via mass-spectrometry. Samples from selected donors (HC n=5, CD n=6, UC n=5) were used to colonize germ-free C57BL/6 mice (n=115) of both sexes. After 3 weeks, the light preference and tail suspension tests were performed to assess anxiety- and depression-like behaviour. Visceral sensitivity was assessed by visceromotor responses to colorectal distension (100-300 μL). Lastly, intestinal inflammation was evaluated by histology and microbiota composition was assessed via 16S rRNA gene sequencing. We observed higher fecal concentrations of LPC and LPA in patients with IBD, mainly in those with chronic abdominal pain. Mice colonized with IBD microbiota displayed a reduced preference for the light compartment and increased immobility, suggestive of anxiety- and depression-like behaviour, respectively. Mice with IBD microbiota had higher visceromotor responses to colorectal distension. Interestingly, we observed increased responses to non-noxious stimuli (100 μL), suggestive of visceral allodynia. Microbiota profiles differed between mice colonized with IBD or HC microbiota. Also, mice with increased visceral sensitivity had lower abundance of Bacteroidales taxa, which contains genes related to the catabolism of LPC and LPA. Histology analysis did not show signs of overt inflammation in the jejunum, ileum, or colon. In conclusion, microbiota from patients with IBD negatively affect the gut-brain axis by inducing changes in anxiety- and depressive-like behaviour and triggering visceral hypersensitivity. Bacterial production of LPC and LPA may be responsible for these deleterious effects. Further studies are needed to understand the underlying molecular mechanisms to guide the development of novel microbiota-based therapies for patients with IBD.

Early-life antibiotic exposure aggravates hepatic steatosis through enhanced endotoxemia and lipotoxic effects driven by gut Parabacteroides.

Compelling evidence supports a link between early-life gut microbiota and the metabolic outcomes in later life. Using an early-life antibiotic exposure model in BALB/c mice, we investigated the life-course impact of prenatal and/or postnatal antibiotic exposures on the gut microbiome of offspring and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Compared to prenatal antibiotic exposure alone, postnatal antibiotic exposure more profoundly affected gut microbiota development and succession, which led to aggravated endotoxemia and metabolic dysfunctions. This was primarily resulted from the overblooming of gut Parabacteroides and hepatic accumulation of cytotoxic lysophosphatidyl cholines (LPCs), which acted in conjunction with LPS derived from Parabacteroides distasonis (LPS_PA) to induce cholesterol metabolic dysregulations, endoplasmic reticulum (ER) stress and apoptosis. Integrated serum metabolomics, hepatic lipidomics and transcriptomics revealed enhanced glycerophospholipid hydrolysis and LPC production in association with the upregulation of PLA2G10, the gene controlling the expression of the group X secretory Phospholipase A2s (sPLA2-X). Taken together, our results show microbial modulations on the systemic MASLD pathogenesis and hepatocellular lipotoxicity pathways following early-life antibiotic exposure, hence help inform refined clinical practices to avoid any prolonged maternal antibiotic administration in early life and potential gut microbiota-targeted intervention strategies.

Enhanced Microglial Engulfment of Dopaminergic Synapses Induces Parkinson's Disease-Related Executive Dysfunction in an Acute LPC Infusion Targeting the mPFC.

The dysfunction of the dopaminergic projection from the ventral tegmental area (VTA) to the medial prefrontal cortex (mPFC) is believed to play a key role in the pathophysiology of Parkinson's disease (PD) accompanied by executive dysfunction (EDF). In this study, we identified an abnormal increase in lysophosphatidylcholine (LPC) levels in PD patients, which closely correlates with the severity of cognitive impairment. LPC disrupts the miR-2885/TDP-43 signaling pathway in microglia, driving dopaminergic presynaptic engulfment. In LPC-exposed mice, microglial activation via miR-2885/TDP-43/p65 signaling led to inflammatory cytokine and complement release, marking dopaminergic synapses for phagocytosis with a "PS/C1q" signal. Following the inhibition of LPC-induced microglial activation through chemogenetic methods, we observed a significant reduction in the phagocytosis of dopaminergic synapses, resulting in improved executive function. The miR-2885 disrupted LPC-induced dopaminergic phagocytosis and alleviated EDF. Furthermore, the accumulation of excessive TDP-43 due to the loss of miR-2885 promoted the engulfment of dopaminergic synapses by facilitating the entry of p65 into the nucleus. Inhibiting TDP-43 levels effectively mitigated LPC-induced EDF. Additionally, supplementing dopamine receptor agonists enhanced the excitability of regional glutamatergic neurons, leading to improved executive function. In summary, LPC exposure in the mPFC impairs microglial regulation, leading to dopaminergic synaptic loss and underactivity of glutamatergic neurons. These changes drive the development of executive dysfunction in PD.

Risk of serum circulating environmental chemical residues to esophageal squamous cell carcinoma: a nested case-control metabolome-wide association study.

Esophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case-control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators.

A70 EXPLORING THE ROLE OF MICROBIAL PHOSPHOLIPIDS IN VISCERAL HYPERSENSITIVITY AND ALTERED EMOTIONAL BEHAVIOUR INDUCED BY INFLAMMATORY BOWEL DISEASE (IBD)-ASSOCIATED MICROBIOTA

Abstract Background IBD is characterized by relapsing episodes of inflammation in the gastrointestinal tract. Abdominal pain is common in IBD and often persists without overt inflammation. Moreover, patients with IBD often develop anxiety and depression, further impairing their quality of life. Recently, gut microbiota emerged as a tentative pathophysiological factor in pain and mood disorders. However, little is known about the specific mechanisms by which microbiota modulate pain and mental health in IBD. Aims We hypothesized that bacteria contribute to visceral hypersensitivity and behavioural abnormalities in IBD via modulation of bioactive phospholipids, focusing on lysophosphatidylcholine (LPC) and its metabolite lysophosphatidic acid (LPA), which were previously linked to chronic pain, anxiety and depression. Methods Fecal samples from healthy controls (HC n=15) and IBD patients (n=35; Crohn’s Disease (CD) n=18, Ulcerative Colitis (UC) n=17) were collected to assess the levels of LPC and LPA via mass-spectrometry. Samples from selected donors (HC n=5, CD n=6, UC n=5) were used to colonize germ-free C57BL/6 mice (n=115) of both sexes. After 3 weeks, the light preference and tail suspension tests were performed to assess anxiety- and depression-like behaviour. Visceral sensitivity was assessed by visceromotor responses to colorectal distension (100-300 μL). Gut inflammation was evaluated by histology. Microbiota composition was assessed via 16S rRNA gene sequencing. Results Fecal concentrations of LPC and LPA were higher in patients with IBD, mainly in those with chronic abdominal pain. Mice colonized with IBD microbiota displayed a reduced preference for the light compartment and increased immobility, suggestive of anxiety- and depression-like behaviour, respectively. Mice with IBD microbiota had higher visceromotor responses to colorectal distension. Interestingly, we observed increased responses to non-noxious stimuli (100 μL), suggestive of visceral allodynia. Microbiota profiles differed between mice colonized with IBD or HC microbiota. Also, mice with increased visceral sensitivity had lower abundance of Bacteroidales taxa, which contains genes related to the catabolism of LPC and LPA. Histology analysis did not show signs of overt inflammation in the jejunum, ileum, or colon. Conclusions Microbiota from patients with IBD negatively affect the gut-brain axis by inducing changes in anxiety- and depression-like behaviour and triggering visceral hypersensitivity. Bacterial production of LPC and LPA may be responsible for these deleterious effects. Funding Agencies CCC, CIHRCrohn’s &amp; Colitis Foundation

Phospholipids and Sphingolipids in Osteoarthritis.

Many studies now emphasize the intricate relationship between lipid metabolism and osteoarthritis (OA), a leading cause of disability. This narrative review examines alterations in the levels of phospholipids (PLs) and sphingolipids (SLs) in synovial fluid (SF), plasma, serum, and articular tissues; discusses their role in joint lubrication, inflammation, and cartilage degradation; and describes their potential as diagnostic markers and therapeutic targets. Key findings include stage-dependent elevated levels of specific PLs and SLs in the SF, blood, and tissue of OA patients, implicating them as possible biomarkers of disease severity and progression. Studies suggest that beyond the involvement of these lipids in joint lubrication, individual species, such as lysophosphatidylcholine (LPC) 16:0, lysophosphatidic acid (LPA), ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P), contribute to pain, inflammation, and degradation of joints through various signaling pathways. Cross-species comparisons suggest that dogs and mice experience similar lipidomic changes during OA as humans, rendering them valuable models for studying lipid-related mechanisms. PLs and SLs in SF appear to originate primarily from the synovial blood capillaries through diffusion. In addition, lipids that are produced locally by fibroblast-like synoviocytes (FLSs) are influenced by cytokines and growth factors that regulate the biosynthesis of PLs for joint lubrication. Emerging research has identified genes such as UGCG and ESYT1 as regulators of lipid metabolism in OA. Further, we examine the suitability of lipids as biomarkers of OA and the potential of targeting the PL and SL pathways to treat OA, emphasizing the need for further research to translate these findings into clinical applications.

Metabolites and Free Fatty Acids in Japanese Black Beef During Wet Aging.

Background: Japanese Black beef is known for its high intramuscular fat content, an important factor in its distinctive Wagyu aroma. Wet aging, which involves vacuum-packing meat and storing it at low temperatures, enhances flavor, texture, and tenderness and is essential for maintaining and improving meat quality. In this study, changes in metabolites and lipid profiles were investigated during the wet aging of Japanese Black and Holstein beef. Methods/Results: Gas chromatography-mass spectrometry identified 113 metabolites in Japanese Black beef and 94 in Holstein beef, with significant increases in metabolites like aspartic acid and maleic acid over the aging period. Regarding lipid composition, total free fatty acids significantly increased with wet aging, with Japanese Black beef showing significantly higher concentrations of oleic and linoleic acids than Holstein beef. Additionally, lipid analysis by liquid chromatography-mass spectrometry revealed a reduction in specific phospholipids, particularly lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), with notable decreases in LPC (18:1), LPC (18:2), LPE (18:1), and LPE (18:2). Conclusions: These results suggest that wet aging influences the stability of membrane lipids, facilitating the degradation of phospholipids into free fatty acids, and improving the flavor of Japanese Black beef.