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Background Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. Methods We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. Results Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. Conclusion The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.

Hepatocellular carcinoma (HCC) is a common malignant tumor, is characterized by an early stage that is not easy to diagnose and a high mortality rate in the late stage, which is a serious threat to patients' lives. Abnormalities in lipid metabolism are closely related to the development of HCC. Integrating transcriptomics and metabolomics analyses can help in the study of drug mechanism of action. Cinobufagin, is the main active ingredient for chinese medicine Chansu to exert anti-tumor effects, but the effects of cinobufagin on abnormal lipid metabolism in tumor cells are not clear. We employed targeted lipid metabolomics to profile alterations in key lipid classes. Furthermore, integrated transcriptomics and metabolomics analyses were conducted to identify critical pathways involved in cinobufagin's action. In this study, we demonstrate through the results of targeted lipid metabolomics that cinobufagin interferes with fatty acyls, sphingolipids, glycerophospholipids, glycerolipids, saccharolipids, and sterol lipids. The results of integration of transcriptomics and metabolomics identified that intervention in fatty acid metabolism (including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, fatty acid degradation, and fatty acid elongation), sphingolipid metabolism (including sphingolipid metabolism, glycosphingolipid biosynthesis-globo and isoglobo series, glycosphingolipid biosynthesis-lacto and neolacto series, glycosphingolipid biosynthesis-ganglio series), and glycerophospholipid metabolism (including glycerophospholipid metabolism, ether lipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis) may be partially responsible for the effect of anti-hepatoma cell growth induced by cinobufagin. Our findings demonstrate that cinobufagin exerts anti-HCC activity partially through lipid metabolism, particularly by targeting fatty acid, sphingolipid, and glycerophospholipid pathways. This study is of great significance for the application of cinobufagin and chansu in clinical HCC treatment and promotes the development of new drugs from traditional Chinese medicine in the field of antitumor.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Eighteen SD rats were divided into three groups: sham‐operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham‐operated group. There were 115 differential metabolites in the model versus electro‐acupuncture group. 117 differential metabolites in the electro‐acupuncture versus sham‐operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.

Cervical cancer is a prevalent gynecological malignancy, and surgical resection can be curative for early-stage disease. Propofol is a commonly used intravenous anesthetic during cervical cancer surgery. However, the effects of propofol on the biological behavior, mRNA transcription, and lipid metabolism of cervical cancer cells remain unclear. In this study, we investigated the impact of clinical-relevant concentrations of propofol on the migration, invasion, transcriptional profiles, and lipid metabolomics of HeLa and C-33 A cells in vitro. HeLa and C-33 A cells were treated with 10 µg/ml propofol or propofol injectable emulsion (PIE). Migration and invasion were assessed using Transwell assays. RNA sequencing (RNA-seq) and liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) were used to analyze mRNA and lipid changes. Western blot was applied to detect enzymes regulating cholesterol metabolism. The key enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) was targeted using siRNA to evaluate cholesterol metabolism. Propofol inhibited the migration of HeLa cells with 0.23-fold compared to control, while PIE restored their migratory capacity. Similarly, propofol reduced the migration of C-33 A cells to 0.22-fold of the control level, whereas PIE restored their migratory ability. RNA-seq, lipid metabolomics and western blot analysis revealed dysregulation of cholesterol metabolism by both propofol and PIE. Specifically, cholesteryl ester and triacylglycerol levels in HeLa and C-33 A cells were altered by propofol treatment, the changes can vary from several folds to hundreds of folds. Propofol modulates cholesterol metabolism in cervical cancer cells, which may impact their migratory potential.

To investigate the cerebrospinal fluid (CSF) lipid metabolite profiles of pediatric patients with purulent meningitis (PM) or viral meningitis (VM) and to explore their differential diagnostic potential. In this proof-of-concept case series, 13 CSF samples from 10 pediatric patients were analyzed by lipidomics, distributed across four sample-level analytical groups: acute-phase PM (PM_A, = 3) and recovery-phase PM (PM_R, = 3) from 3 PM patients with paired sampling, acute-phase VM (VM_A, = 3) from 3 VM patients, and non-meningitic controls (N, = 4). Lipid separation and detection were performed by UPLC-MS/MS on a Q Exactive high-resolution mass spectrometer, and data were processed using LipidSearch v.4.1. Compared with the N group, the PM_A group displayed exploratory lipid alterations with 30 increased and 45 decreased metabolites, predominantly involving sphingolipid (SPH), dihexosylceramide (Hex2Cer), monohexosylceramide (Hex1Cer), lysophosphatidylcholine (LPC), and acylcarnitine (AcCa) species. Elevated Hex2Cer combined with reduced SPH represented a distinctive exploratory PM_A pattern. Receiver operating characteristic (ROC) analysis identified LPC(20:3) and Hex2Cer(d42:3) as exploratory candidate features for distinguishing PM_A from N (apparent AUC = 0.833 for each marker; leave-one-out jackknife AUC range 0.750-1.000, mean 0.833). Multi-feature composite AUCs were not reported because, at = 7, any composite would be highly susceptible to overfitting. The VM_A group showed limited deviation from N (4 increased, 6 decreased metabolites) but differed from PM_A in 32 increased and 15 decreased metabolites, primarily within SPH, phosphatidylserine (PS), MePC, LPC, and AcCa subclasses. SM(d35:2) emerged as an exploratory candidate distinguishing VM_A from both N and PM_A, but at = 3 vs. 4 the apparent AUC = 1.000 is statistically expected for some of the 344 screened metabolites by chance alone, and the candidate is therefore hypothesis-generating only. Cerebrospinal fluid lipidomics revealed disease-stage-specific alterations in pediatric PM and VM. These findings should be regarded as hypothesis-generating in this small proof-of-concept cohort and require validation in larger pediatric studies.

Background: Glycyrrhizic acid (GA) has been reported to be liver protective; however, the characters and underlying mechanisms of GA against tripterygium glycoside tablet (TGT)-induced acute liver injury remain unelucidated. Hypothesis/Purpose: We assumed that GA could relieve TGT-induced acute liver injury by regulating liver function-related genes and lipid metabolites. Study Design: TGT-induced acute liver injury models were constructed in vivo and in vitro . Then the liver protective effect and mechanisms of GA were investigated by a combination of transcriptome, lipid metabolomics, and experimental validation. Methods: Intraperitoneal injection of GA was given in advance for six successive days. Then, the TGT-induced acute liver injury model was constructed by a single oral administration of TGT at 270 mg/kg, except for the normal group. All animals were sacrificed 18 h later. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) were quantified. Liver tissues were used to observe pathological changes through hematoxylin–eosin (HE) staining and selected for transcriptome and metabolome sequencing. The underlying mechanisms were analyzed and further validated both in vivo and in vitro . Results: Pre-administration of GA markedly decreased the serum concentrations of AST, ALT, ALP, and TBIL but increased those of SOD and GSH-Px, improving the liver morphology of mice with TGT-induced acute liver injury. In addition, GA significantly increased the gene levels of Cyp2b13, Cyp2c69, Cyp3a16, Cyp3a44, Fmo3, and Nipal1. Differentially accumulated metabolites were screened and classified as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The in vitro results indicated that pre-administration of GA markedly alleviated the inhibitory effect of TGT on BRL-3A activity. Conclusion: This study combined transcriptome, lipid metabolomics, and experimental validation to offer convincing evidence that GA alleviates TGT-induced acute liver injury partially by regulating the activities of CYP and the metabolism of PC and PE.

Background Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity. Methods Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected. Results The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2 + Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2 + Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2 . The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2 + Mono/Mac during ACLF. Conclusions The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2 + macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.

Heat stress (HS) by high-temperature environment reduced the production performance of poultry and caused losses to the breeding industry. The present study was conducted to investigate the effects of HS on serum lipidomics in Chinese indigenous slow-growing broiler chickens (Huaixiang chickens). A total of 40 8-week-old female Huaixiang chickens were randomly allocated to two groups, including normal temperature (NT, fed basal diet) and HS (fed basal diet), and each group consisted of five replicates with four birds per replicate. NT and HS groups were exposed to 21.3 ± 1.2 °C and 32.5 ± 1.4 °C for 4 weeks, respectively. Serum lipidomics in broilers was determined by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. The results indicated that there were significant differences in metabolic spectra between the groups, and a total of 17 differential metabolites were screened. Compared with NT group, HS group reduced the serum ceramide (cer) (d18:1/22:0), cer (d18:1/24:1), cer (d20:2/22:2), lyso-phosphatidylcholine (LPC) (18:0), phosphatidylcholine (PC) (18:0/20:4), PC (15:0/23:4), PC (18:0/22:6), PC (18:2/18:2), phosphatidylethanolamine (PE) (18:1/18:1), polyethylene terephthalate (PEt) (37:3/8:0), phosphatidylglycerol (PG) (32:1/16:2), phosphatidyl methyl ethanolamine (PMe) (19:3/13:0), PMe (26:1/9:0), sphingomyelin (SM) (d16:0/18:1), triglycerides (TG) (18:0/18:1/18:2), and TG (19:4/21:6/21:6) levels [variable importance in the projection ( VIP > 1 and P < 0.05)], while HS group increased serum PC (17:0/17:0) content ( VIP > 1 and P < 0.05). Also, metabolic pathway analysis showed that the pathways of glycerolphospholipid, linoleic acid and α-linolenic acid metabolism, and glycosylphosphatidylinositol (GPI)-anchored biosynthesis were changed ( P < 0.05). In conclusion, HS led to the disorders of serum lipid metabolism in broilers, and mainly downregulated serum content of phospholipids. These findings provide novel insights into the effects of HS on serum lipidomics in indigenous slow-growing chickens.

Background Acne vulgaris (AV) is a common inflammatory skin disease during adolescence. Metformin (MET) has recently been found to have the effects of regulating lipid disorders, suggesting its potential benefits in the treatment of AV patients. Method Recruited 18 patients with moderate to severe AV, and then received MET treatment (AVM group) for a continuous period of 12 weeks, while 20 healthy controls (HC group) served as the control group. The Global Acne Grading System (GAGS) score and VISIA‐CRTM imaging system were used to evaluate the severity of AV patients before and after treatment, and the serum lipid metabolomics differences were detected by liquid chromatograph mass spectrometer (LC–MS) before and after treatment. Multivariate statistical analysis of differentially expressed lipid metabolites was performed using partial least squares discriminant analysis (PLS‐DA) and orthogonal partial least squares discriminant analysis (OPLS‐DA). The Mann–Whitney U test was used to analyze the differences in lipid metabolites between groups. Spearman correlation analysis was conducted to examine the correlation between differentially expressed serum lipid metabolites and the acne severity index. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to predict the metabolic pathways involved in the differentially expressed lipid metabolites in the AVM group. Results Compared to before treatment, the GAGS score (p < 0.001), red zone (p < 0.001) and Porphyrin (p < 0.01) indices of AV patients significantly improved after oral administration of MET. The results of PLS‐DA and OPLS‐DA indicated a clear separation in the composition of lipid metabolites between AV patients and the HC group; however, after MET treatment, the composition of lipid metabolites in AV patients showed a trend towards resembling that of the HC group. The 25 lipid metabolites with the most significant differences between AV patients and the HC group were all restored to the levels of the HC group after MET treatment. The Spearman correlation results showed that the serum PC (16:1/22:6) concentration in AV patients before treatment was positively correlated with the porphyrin area index (r = 0.47, p = 0.049). The KEGG analysis revealed 6 metabolic pathways that showed significant downregulation after treatment with MET. Conclusion The therapeutic effect of MET on patients with moderate to severe AV may be achieved through the positive regulation of lipid metabolism. Its molecular mechanism may be related to the downregulation of inflammatory mediators associated with choline metabolism and arachidonic acid metabolism.

Fat deposition traits are influenced by genetics and environment, which affect meat quality, growth rate, and energy metabolism of domestic animals. However, at present, the molecular mechanism of fat deposition is not entirely understood in beef cattle. Therefore, the current study conducted transcriptomics and lipid metabolomics analysis of subcutaneous, visceral, and abdominal adipose tissue (SAT, VAT, and AAT) of Huaxi cattle to investigate the differences among these adipose tissues and systematically explore how candidate genes interact with metabolites to affect fat deposition. These results demonstrated that compared with SAT, the gene expression patterns and metabolite contents of VAT and AAT were more consistent. Particularly, SCD expression, monounsaturated fatty acid (MUFA) and triglyceride (TG) content were higher in SAT, whereas PCK1 expression and the contents of saturated fatty acid (SFA), diacylglycerol (DG), and lysoglycerophosphocholine (LPC) were higher in VAT. Notably, in contrast to PCK1, 10 candidates including SCD, ELOVL6, ACACA, and FABP7 were identified to affect fat deposition through positively regulating MUFA and TG, and negatively regulating SFA, DG, and LPC. These findings uncovered novel gene resources and offered a theoretical basis for future investigation of fat deposition in beef cattle.