Lipid Metabolism Pathways Research Articles

Impacts of polyhydroxybutyrate (PHB) microplastic exposure on physiology and metabolic profiles of Litopenaeus vannamei

In light of increasing concerns about microplastic pollution, it is crucial to understand the biological impacts of biodegradable PHB microplastics on marine organisms. This study included a 96-h exposure experiment to assess acute toxicity at PHB concentrations of 0 mg/L, 100 mg/L, 500 mg/L and 1000 mg/L. Additionally, a 60-day feeding trial was conducted with PHB concentrations of 0, 0.5, 1.0 and 2.0 g/kg to evaluate the long-term effects on growth, physiological health and metabolic responses of Litopenaeus vannamei. Results from the exposure experiment indicated that PHB microplastics up to 100 mg/L were non-toxic to shrimp. However, the 60-day feeding trial revealed that higher concentrations led to slight reductions in survival rates and growth performance, indicating a concentration-dependent response. Analysis of antioxidant and immune enzymes showed minimal changes across most parameters. However, increases in malondialdehyde content and lysozyme activity at higher PHB levels suggested a stress response. Microbial analysis indicated higher species richness and greater community diversity in the PHB group compared to controls, as evidenced by Chao1, ACE, Shannon and Simpson indices. Linear discriminant analysis revealed that Enterobacteriales and related taxa were more prevalent in the PHB group, while Rhodobacteraceae and associated taxa dominated the control group. Pathway analysis highlighted enhanced signal transduction, cell mobility and metabolic resource reallocation in response to PHB-induced stress. Integrated transcriptomic and metabolomic analyses revealed significant regulatory changes, especially in lipid metabolism pathways. These findings suggest that while PHB microplastics trigger adaptive metabolic responses in shrimp, they do not cause acute toxicity. Significant variations in intestinal microbiome composition reflect potential shifts in gut health dynamics due to PHB ingestion. This study enhances our understanding of the ecological impacts of microplastics and underscores the necessity for further research into the environmental safety of biodegradable alternatives.

Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome

BackgroundChanges in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS.MethodsGene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model.Results19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968–1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses.ConclusionA novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

LC/MS-Based Untargeted Lipidomics Reveals Lipid Signatures of Sarcopenia.

Sarcopenia, a multifactorial systemic disorder, has attracted extensive attention, yet its pathogenesis is not fully understood, partly due to limited research on the relationship between lipid metabolism abnormalities and sarcopenia. Lipidomics offers the possibility to explore this relationship. Our research utilized LC/MS-based nontargeted lipidomics to investigate the lipid profile changes as-sociated with sarcopenia, aiming to enhance understanding of its underlying mechanisms. The study included 40 sarcopenia patients and 40 control subjects matched 1:1 by sex and age. Plasma lipids were detected and quantified, with differential lipids identified through univariate and mul-tivariate statistical analyses. A weighted correlation network analysis (WGCNA) and MetaboAna-lyst were used to identify lipid modules related to the clinical traits of sarcopenia patients and to conduct pathway analysis, respectively. A total of 34 lipid subclasses and 1446 lipid molecules were detected. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified 80 differen-tial lipid molecules, including 38 phospholipids. Network analysis revealed that the brown module (encompassing phosphatidylglycerol (PG) lipids) and the yellow module (containing phosphati-dylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) lipids) were closely associated with the clinical traits such as maximum grip strength and skeletal muscle mass (SMI). Pathway analysis highlighted the potential role of the glycerophospholipid metabolic pathway in lipid me-tabolism within the context of sarcopenia. These findings suggest a correlation between sarcopenia and lipid metabolism disturbances, providing valuable insights into the disease's underlying mechanisms and indicating potential avenues for further investigation.

Unveiling the multifaceted role of adropin in various diseases (Review).

Adropin is a secreted peptide encoded by the energy homeostasis‑associated gene, which also functions as a membrane‑bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non‑alcoholic fatty liver disease/non‑alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.

Metabolic Profiling Analysis of Congenital Adrenal Hyperplasia via an Untargeted Metabolomics Strategy.

Congenital adrenal hyperplasia (CAH) manifests as an autosomal recessive disorder characterized by defects in the enzymes responsible for steroid synthesis. This work aims to perform metabolic profiling of patients with CAH, screen key differential metabolites compared to the control group, and discover the associated metabolic pathways implicated in CAH. Serum samples obtained from 32 pediatric male patients with CAH and 31 healthy control group candidates were subjected to analysis using non-targeted metabolomics strategy using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 278 differential metabolites were identified and annotated in KEGG. Operating characteristic curves (ROC) measurement exhibited 9 metabolites exhibiting high efficacy in differential diagnosis, as evidenced by an area under ROC curve (AUC) exceeding 0.85. Pathway analysis uncovered notable disruptions in steroid hormone biosynthesis (p <0.0001), purine metabolism and irregularities in lipid metabolism and amino acid metabolism, including tyrosine and alanine, in CAH patients. These findings demonstrate that metabolic pathways of purine, amino acid and lipid metabolism, apart from steroid hormone biosynthesis, may be disrupted and associated with CAH. This study helps provide insight into the metabolic profile of CAH patients and offers a new perspective for monitoring and administering follow-up care to CAH patients.

Effects of ammonia nitrogen stress on the physiological, biochemical, and metabolic levels of the gill tissue of juvenile four-finger threadfin (Eleutheronema tetradactylum)

In this study, the impact of ammonia nitrogen stress on juvenile four-finger threadfin in pond culture was examined. The 96-hour median lethal concentration (LC50-96h) and safe concentration of ammonia nitrogen were assessed in juveniles with a body weight of 7.4 ± 0.6 g using ecotoxicological methods. The study design included a stress group exposed to LC50-96h levels of ammonia nitrogen and a control group without ammonia nitrogen exposure. To examine the physiological, biochemical, and metabolic effects of ammonia nitrogen on gill tissue, gill tissue samples were collected after 12, 24, 48, and 96 h of stress, with a resumption of treatment after 48 h. Compared to the control group, ammonia nitrogen adversely affected juvenile four-finger threadfin, with LC50-96h and safe concentration values of 20.70 mg/L and 2.07 mg/L, respectively. Exposure to ammonia nitrogen resulted in substantial gill damage, including fusion of lamellae, epithelial cell loss, and proliferation of chlorine-secreting cells. This tissue damage persisted even after a 48-h recovery period. Ammonia nitrogen stress triggered an increase in antioxidant enzyme activity (superoxide dismutase, catalase, and glutathione peroxidase) and malondialdehyde levels in gills, indicating oxidative stress from 12 h onwards. Although enzyme activity decreased over time, oxidative stress persisted even after recovery, suggesting an ongoing need for antioxidant defense. Metabolomics analysis showed significant alterations in 423 metabolites under ammonia nitrogen stress. Key metabolites such as L-arginine, taurine, 20-hydroxyarachidonic acid, 11,12-dihydroxy-5Z, 8Z, and 14Z eicosotrienic acid followed an increasing trend; uridine, adenosine, L-glutathione, and thymidine 5′-triphosphate followed a decreasing trend. These changes reflect metabolic adaptations to stress. In enriched metabolic pathways, the main differential pathways are membrane transport, lipid metabolism, and amino acid metabolism. After 48 h, significant differences were observed in 396 metabolites compared to the control group. Notably, L-arginine, choline, and L-histidine increased, while linoleic acid, adenosine, and glutathione decreased. Amino acid and lipid metabolism pathways were key affected pathways. Under ammonia nitrogen stress, juvenile four-finger threadfin increased the synthesis of unsaturated and saturated fatty acids to cope with low temperatures and bolster immune function by consuming spermidine. This adaptation helps to clear peroxides generated during fatty acid synthesis, thereby protecting cells from oxidative damage. This study provides insights for pond aquaculture and breeding of ammonia nitrogen-tolerant fish strains.

High-Protein Mulberry Leaves Improve Glucose and Lipid Metabolism via Activation of the PI3K/Akt/PPARα/CPT-1 Pathway.

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications.

Exploring molecular mechanisms underlying changes in lipid fingerprinting of salmon (Salmo salar) during air frying integrating machine learning-guided REIMS and lipidomics analysis

Lipid oxidation in air-fried seafood poses a risk to human health. However, the effect of a prooxidant environment on lipid oxidation in seafood at different air frying (AF) temperatures remains unknown. An integrated machine learning (ML) - guided REIMS and lipidomics method was applied to explore lipid profiles, lipid oxidation, and lipid metabolic pathways of salmons under different AF temperatures (140, 160, 180, and 200 °C). A significant difference in the lipidomic fingerprinting of air-dried salmon at different temperatures was shown by the main ML methods (neural networks, support vector machines, ensemble learning, and naïve bayes). In total, 773 differential expression metabolites (DEMs) were identified, including glycerophospholipids (GPs), glycerides (GLs), and sphingolipids. A total of 34 DEMs with p values <0.05 and variable importance of projection values >1.0 were analyzed, belonging to linoleic acid metabolism, GL metabolism, and GP metabolism pathways. Correlation network analysis revealed that some characteristic DEMs (phosphatidylcholine, lyso-phosphatidylcholine, triglycerides, fatty acids, and phosphatidylethanolamine) were highly correlated with lipid oxidation. In addition, variations of volatile compounds, color values, texture characteristics, and thiobarbituric acid-reactive substance values were analyzed to corroborate the oxidation characteristics.

Proteomic Profiling of Cocos nucifera L. Zygotic Embryos during Maturation of Dwarf and Tall Cultivars: The Dynamics of Carbohydrate and Fatty Acid Metabolism.

There is a limited number of studies analyzing the molecular and biochemical processes regulating the metabolism of the maturation of Cocos nucifera L. zygotic embryos. Our research focused on the regulation of carbohydrate and lipid metabolic pathways occurring at three developmental stages of embryos from the Mexican Pacific tall (MPT) and the Yucatan green dwarf (YGD) cultivars. We used the TMT-synchronous precursor selection (SPS)-MS3 strategy to analyze the dynamics of proteomes from both embryos; 1044 and 540 proteins were determined for the MPT and YGD, respectively. A comparison of the differentially accumulated proteins (DAPs) revealed that the biological processes (BP) enriched in the MPT embryo included the glyoxylate and dicarboxylate metabolism along with fatty acid degradation, while in YGD, the nitrogen metabolism and pentose phosphate pathway were the most enriched BPs. Findings suggest that the MPT embryos use fatty acids to sustain a higher glycolytic/gluconeogenic metabolism than the YGD embryos. Moreover, the YGD proteome was enriched with proteins associated with biotic or abiotic stresses, e.g., peroxidase and catalase. The goal of this study was to highlight the differences in the regulation of carbohydrate and lipid metabolic pathways during the maturation of coconut YGD and MPT zygotic embryos.

Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia.

Macrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia. Single-cell RNA-seq of CD45+ transition zone leukocytes from 10 large (>90 grams) and 10 small (<40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes. BPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature preferentially accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated by TREM2 and MARCO expression, significantly accumulate with increased prostate volume. TREM2+ and MARCO+ macrophage abundance positively correlates with patient body mass index and urinary symptom scores. TREM2+ macrophages have significantly higher neutral lipid than TREM2- macrophages from BPH tissues. Lipid-rich macrophages were observed to localize within the stroma in BPH tissues. In vitro studies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages. These data define two new BPH immune subpopulations, TREM2+ and MARCO+ macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.

Single-cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism-related mechanisms.

The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1-type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. By utilising single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co-culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage-derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage-derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage-derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation-associated proteins in tumour tissues was examined using immunohistochemistry. Through combined analysis of scRNA-seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage-derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.

Unlocking Secrets: Lipid Metabolism and Lipid Droplet Crucial Roles in SARS-CoV-2 Infection and the Immune Response.

Lipid droplets (LD) are crucial for maintaining lipid and energy homeostasis within cells. LDs are highly dynamic organelles that present a phospholipid monolayer rich in neutral lipids. Additionally, LDs are associated with structural and non-structural proteins, rapidly mobilizing lipids for various biological processes. Lipids play a pivotal role during viral infection, participating during viral membrane fusion, viral replication, and assembly, endocytosis, and exocytosis. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection often induces LD accumulation, which is used as a source of energy for the replicative process. These findings suggest that LDs are a hallmark of viral infection, including SARS-CoV-2 infection. Moreover, LD participates in the inflammatory process and cell signaling, activating pathways related to innate immunity and cell death. Accumulating evidence demonstrates that LD induction by SARS-CoV-2 is a highly coordinated process, aiding replication and evading the immune system, and may contribute to the different cell death process observed in various studies. Nevertheless, recent research in the field of LDs suggests these organelles according to the pathogen and infection conditions may also play roles in immune and inflammatory responses, protecting the host against viral infection. Understanding how SARS-CoV-2 influences LD biogenesis is crucial for developing novel drugs or repurposing existing ones. By targeting host lipid metabolic pathways exploited by the virus, it is possible to impact viral replication and inflammatory responses. This review seeks to discuss and analyze the role of LDs during SARS-CoV-2 infection, specifically emphasizing their involvement in viral replication and the inflammatory response.

Alterations in the Salivary Microbiome and Metabolism in Patients With Carotid Atherosclerosis from Rural Northeast China.

Periodontitis and atherosclerosis are both chronic inflammatory diseases with a high prevalence. Increasing evidence supports the independent association between severe periodontitis and atherosclerotic cardiovascular disease, in which oral microorganisms may play an important role. We aimed to evaluate the characteristic changes of salivary microbiome and metabolome in patients with carotid atherosclerosis (CAS) and periodontitis. The subjects were obtained from a cross-sectional study that included 1933 participants aged 40 years or older from rural northeast China. The study enrolled 48 subjects with CAS and 48 controls without CAS matched by sex, age, body mass index, and prevalence of hypertension, diabetes, and dyslipidemia. We performed full-length 16S rDNA gene sequencing and untargeted metabolomics of saliva samples from 96 subjects. We found that CAS was closely associated with an increased abundance of Streptococcus, Lactobacillus, and Cutibacterium. Furthermore, patients with CAS had higher prevalence of severe periodontitis than the control group. Notably, periodontal pathogens such as Tannerella and Anaeroglobus were not only associated with periodontitis but also enriched in patients with CAS, whereas periodontal health-associated Neisseria was more abundant in those without CAS. We also identified 2 lipid metabolism pathways, including glycerophospholipid and sphingolipid metabolism, as associated with CAS. The levels of trimethylamine N-oxide and inflammatory mediator leukotriene D4 were significantly higher in patients with CAS, whereas the levels of carnosine were significantly lower, than those in controls. Additionally, serum levels of inflammatory marker high-sensitivity C-reactive protein were significantly increased in CAS and positively correlated with the abundance of Anaeroglobus and leukotriene D4 in saliva. Our study suggests that characteristic changes in salivary microbiota and metabolites are closely related to CAS, and periodontitis and associated microorganisms may be involved in the initiation and progression of CAS.

The PAH1-encoded phosphatidate phosphatase of Yarrowia lipolytica differentially affects gene expression and lipid biosynthesis

Yarrowia lipolytica is a model oleaginous yeast with a strong capacity for lipid accumulation, yet its lipid metabolic pathways and regulatory mechanisms remain largely unexplored. The PAH1-encoded phosphatidate (PA) phosphatase governs lipid biosynthesis by its enzymatic activity and regulating the transcription of genes involved in phospholipid biosynthesis. In this work, we examined the effect of the loss of Pah1 (i.e., pah1Δ) on cell metabolism in cells growing in low- and high-glucose media. Multi-omics analyses revealed the global effect of the pah1Δ mutation on lipid and central carbon metabolism. Lipidomics analyses showed that the pah1Δ mutation caused a massive decrease in the masses of triacylglycerol (TAG) and diacylglycerol (DAG), and these effects were independent of glucose concentration in the media. Conversely, phospholipid levels declined in low-glucose media but increased in high-glucose media. The loss of Pah1 affected the expression of genes involved in key pathways of glucose metabolism, such as glycolysis, citric acid cycle, oxidative phosphorylation, and the pentose phosphate pathway, and these effects were more pronounced in high-glucose media. In lipid biosynthesis, the genes catalyzing phosphatidylcholine (PC) synthesis from phosphatidylethanolamine (PE) were upregulated within the CDP-DAG pathway. In contrast, PC synthesis through the Kennedy pathway was downregulated. The ethanolamine branch of the Kennedy pathway that synthesizes PE was also upregulated in pah1Δ. Interestingly, we noted a massive increase in the levels of lysophospholipids, consistent with the upregulation of genes involved in lipid turnover. Overall, this work identified novel regulatory roles of Pah1 in lipid biosynthesis and gene expression.

Viral metagenomics combined with non-targeted serum metabolomics reveals the role of enteroviruses in a mouse model of coronary heart disease

BackgroundCoronary heart disease (CHD) is a common cardiovascular disease that is associated with altered gut microbiota. Enteroviruses, an essential component of the gut microbiome, may play an important role in disease progression. However, the relationship between enteroviruses and CHD remains unclear. The development of high-throughput sequencing technologies has facilitated research on the interconnections between viruses and disease-related metabolites.Methods and resultsMice were fed a high-fat diet (CHD group) or chow diet (Sham group) for 12 weeks, and ligation of the left anterior descending coronary artery was performed at the end of week 8. After 4 weeks, all animals were euthanised. Subsequently, the animals were evaluated for basic haemato-biochemical parameters and cardiac function, and aorta staining was performed. Based on enteroviral metagenomics and serum UPLC–MS/MS metabolomics analyses, we evaluated the association between enteroviral groups and serum metabolites of CHD mouse model. A high-fat diet and coronary ligation enabled the establishment of the CHD mouse model. Notably, the enterovirus spectrum of the sham group was significantly different from that of the CHD group, with 24 viral communities of different family and species classification, such as Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus, exhibiting significant differences. In addition, 731 Differential metabolites were detected in the serum of both groups of mice. Correlation network analysis revealed a close relationship between various metabolites related to lipid metabolism and different viruses, including Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus.ConclusionsAn animal model of CHD, characterised by lipid disturbance and myocardial ischaemia, was established using a high-fat diet and ligation of the left anterior descending branch of the coronary artery. Tsarbombavirus, Firehammervirus, Mingyongvirus, and Claudivirus were associated with metabolites in the lipid metabolism pathway. The results indicate that Tsarbombavirus may be the main genus interacting with CHD-related metabolites in mice. Conclusively, the findings of our study provide novel insights into the potential relationship enterovirus groups and metabolites associated with CHD.

Response signatures of intestinal microbiota and gene transcription of yellow catfish (Pelteobagrus fulvidraco) to Aeromonas hydrophila infection

Bacterial intestinal inflammation is a common disease of yellow catfish (Pelteobagrus fulvidraco) in high-density aquaculture. Understanding the interactions between host and intestinal bacteria is helpful to intestinal inflammatory disease control. Here, we constructed a model of intestinal inflammation after Aeromonas hydrophila infection in yellow catfish, and characterized variations in gene expression and microbiome in the gut through high-throughput sequencing. Furthermore, host gene-microbiome interactions were identified. Histology observation showed disordered distribution of columnar epithelial cells and decrease of goblet cells in intestine. A total of 4741 genes showed differentially expression, mostly in comparisons between 12 hpi group with each other groups respectively, including control, 24 hpi and 48 hpi groups. These genes were enriched in immune-related pathways including the IL-17 signaling pathway, triggering strong inflammatory response at the invading stage within 12 h. Subsequently, the host strengthened energy consumption by activating carbohydrate and lipid metabolism pathways to repair the intestinal mucosal immune defense line. In addition, fish with A. hydrophila infection show decreased richness of gut microbial, reduced relative abundance of probiotics including Akkermansia, and elevated pathogenic bacteria such as Plesimonas. An integrative analysis identified A. hydrophila-related genes, such as il22 and stat3, for which expression level is close associated with the shift of A. hydrophila-related bacteria relative abundance, such as Akkermansia and Cetobacterium. Aside from picturing the variations of intestine gene expression and mucosal microbiome of yellow catfish coping with A. hydrophila infection, our study probed the underlying host-microbe interactions in A. hydrophila infection induced intestinal inflammatory, providing new insights for disease control in aquaculture.

Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study

BackgroundThe relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD.MethodsWe established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis.ResultsAlthough H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.”ConclusionsClinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

A comprehensive foodomics analysis of rambutan seed oils: Focusing on the physicochemical parameters, lipid concomitants and lipid profiles

A foodomics approach was employed to systematically characterize and compare the quality parameters, antioxidant activity, minor-components, fatty acid composition, and lipid profiles of the seed oils from the three most popular rambutan varieties in China. The total lipid content ranged from 23.40 to 25.77 g/100 g. The fatty acids 9cC18:1 (39.84%–40.92%) and C20:0 (28.45%–30.23%) were identified as the dominant ones, which are uncommon among higher plants. All oil samples exhibited low AI and TI values. BR-7 exhibited the highest levels of squalene (21.48 mg/kg), cholesterol (144.43 mg/kg), and tocopherol (17.42 mg/kg), and the lowest levels of polyphenols (24.21 mg GAE/kg). Additionally, a total of 807 lipid species were identified, with TAG, DGTS, and PE being the predominant ones. Multivariate statistical analyses revealed significant variations in lipid profiles among the varieties, particularly in glycerophospholipids and sphingolipids. Fifty-seven distinct lipids were identified as potential markers for distinguishing between rambutan varieties. Furthermore, a hypothetical scenario was developed by linking relevant lipid metabolism pathways. These findings establish a theoretical framework for comprehending rambutan seed oil in depth and unlocking its high-value potential.

Mechanisms of Puerariae Lobatae Radix in regulating sebaceous gland secretion: insights from network pharmacology and experimental validation.

This research aims to explore how Puerariae Lobatae Radix regulates sebaceous gland secretion using network pharmacology, and validate its effects on important targets through animal studies. This study utilized UPLC-EQ-MS to analyze Puerariae Lobatae Radix extract and identify potential bioactive compounds. Predicted targets of these compounds were obtained from the Swiss Target Prediction database, while targets associated with sebaceous gland secretion were obtained from the GeneCards database. Common targets between the databases were identified and a protein-protein interaction (PPI) network was established using the STRING platform. The PPI network was further analyzed using Cytoscape software. Pathway enrichment analysis was performed using Reactome, and molecular docking experiments targeted pivotal pathway proteins. Animal experiments were then conducted to validate the regulatory effects of the primary active compounds of Puerariae Lobatae Radix on key pathway proteins. This research identified 17 active compounds in Puerariae Lobatae Radix and 163 potential targets associated with the regulation of sebum secretion. Pathway enrichment analysis indicates that these targets may modulate lipid metabolism pathways through involvement in peroxisome proliferator-activated receptor α, SREB, steroid metabolism, and arachidonic acid metabolism pathways. Molecular docking analysis demonstrates that puerarin and daidzein show favorable binding interactions with key targets in these pathways. Animal experiments demonstrated that the administration of Puerariae Lobatae Radix resulted in a significant reduction in the area of sebaceous gland patches compared to the control group. Histological analysis revealed notable alterations in the structure of sebaceous glands, including reductions in size, thickness, and density. Furthermore, the expression levels of TG, DHT, and IL-6 were significantly decreased in the Puerariae Lobatae Radix group (p < 0.05), and immunoblotting indicated a significant decrease in the expression of PPARG and ACC1 (p < 0.05). This study demonstrates that Puerariae Lobatae Radix can regulate skin lipid metabolism by targeting multiple pathways. The primary mechanism involves inhibiting sebaceous gland growth and reducing TG secretion by modulating the expression of PPARG and ACC1. Puerarin and Daidzein are identified as key bioactive compounds responsible for this regulatory effect. These findings highlight the therapeutic potential of Puerariae Lobatae Radix in addressing sebaceous gland-related conditions.

Metabolomics analysis based on UHPLC-QTOF-MS/MS to explore the synthesis mechanism and culture conditions optimization of Penicillium EF-2 exopolysaccharide

Penicillium exopolysaccharide (EPS) inhibits galactose lectins and enhances immunity. However, EPS production is low and its synthesis mechanism remains unclear. Penicillium EF-2 strains with high EPS production were selected for this study, and Penicillium fermentation conditions were subsequently improved. The optimal culture conditions were 30 g/L lactose, 6 g/L yeast extract powder, 4 d seed age, 10 % inoculation amount, 3 d of secondary fermentation time, and the final EPS yield was 3.97 g/L. UHPLC-Q-TOF-MS/MS was used to explore the mechanism of EPS synthesis at the metabolic level. Optimal carbon source: lactose and optimal nitrogen source: yeast extract can provide precursors for EPS synthesis through related metabolic pathways. Moreover, regulating the energy, vitamin, and lipid metabolic pathways created favourable conditions for EPS synthesis and secretion. These findings explain the mechanism of EPS synthesis at the metabolic level and provide a theoretical basis for optimising and industrialising EPS production.