Changes In Metabolites Research Articles

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

BACKGROUND Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.

Association of Indoleamine 2,3-Dioxygenase (IDO) Activity with Outcome after Cardiac Surgery in Adult Patients.

Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (-2.298, 95% CI -4.028 to -596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients.

Genotoxicity and metabolic changes induced via ingestion of virgin and UV-aged polyethylene microplastics by the freshwater fish Perca fluviatilis

The present study aims to compare and assess the toxicity induced by aged (irradiated with ultraviolet radiation for 120 days) polyethylene microplastics (PE-MPs) in comparison to virgin (non-irradiated) ones, after feeding the freshwater fish Perca fluviatilis. To this end, MPs mediated genotoxicity was assessed by the investigation of micronucleus nuclear abnormalities frequency in fish blood, and the degree of DNA damage in the liver and muscle tissues, while metabolic alterations were also recorded in both tissues. Results showed that both virgin and aged PE-MPs induced signaling pathways leading to DNA damage and nuclear abnormalities, as well as metabolites changes in all tissues studied. Metabolic changes revealed that the metabolism of nucleic acids, energy, amino acids, and neurotransmitters was more disrupted in the liver and by aged PE-MPs compared to muscles. Fish fed with aged PE-MPs exhibited greater DNA damage, while blood cells of fish fed with virgin PE-MPs seemed to be more vulnerable to nuclear abnormalities in relation to those fed with aged PE-MPs. Moreover, aged PE-MPs induced more acute overall effects on the metabolic profiles of fish tissues, and initiated stronger stress responses, inflammation, and cellular damages in fish tissues in relation to virgin ones. Characterization of both virgin and aged MPs revealed that the latter exhibited lower crystallinity and melting point, more irregular shapes and higher moiety of oxygen and carbonyl groups, which could be attributed for their observed higher toxicity. The research outcomes provide significant insights for advancing toxicological investigations in this field.

A high-fat diet induces changes in mesenteric adipose tissue accelerating early-stage pancreatic carcinogenesis in mice

Increased adiposity is a significant risk factor for pancreatic cancer development. Multiple preclinical studies have documented that high-fat, high calorie diets, rich in omega-6 fatty acids (FA) accelerate pancreatic cancer development. However, the effect of a high-fat, low sucrose diet (HFD), on pancreatic carcinogenesis remains unclear. We evaluated the impact of a HFD on early-stage pancreatic carcinogenesis in the clinically relevant KrasLSL-G12D/+; Ptf1aCre/+ (KC) genetically engineered mouse model, and characterized the role of the mesenteric adipose tissue (MAT). Cohorts of male and female KC mice were randomly assigned to a control diet (CD) or a HFD, matched for FA composition (9:1 of omega-6 FA: omega-3 FA), and fed their diets for 8 weeks. After 8 weeks on a HFD, KC mice had significantly higher body weight, fat mass, and serum leptin compared to CD-fed KC mice. Furthermore, a HFD accelerated pancreatic acinar-to-ductal metaplasia (ADM) and proliferation, associated with increased activation of ERK and STAT3, and macrophage infiltration in the pancreas, compared to CD-fed KC mice. Metabolomics analysis of the MAT revealed sex differences between diet groups. In females, a HFD altered metabolites related to FA (α-linolenic acid and linoleic acid) and amino acid metabolism (alanine, aspartate, glutamate). In males, a HFD significantly affected pathways related to alanine, aspartate, glutamate, linoleic acid, and the citric acid cycle. A HFD accelerates early pancreatic ADM through multifaceted mechanisms, including effects at the tumor and surrounding MAT. The sex-dependent changes in MAT metabolites could explain some of the sex differences in HFD-induced pancreatic ADM.

Fecal microbiota and concentrations of long-chain fatty acids, sterols, and unconjugated bile acids in cats with chronic enteropathy.

Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE), inflammatory bowel diseases (IBD), and low-grade intestinal T-cell lymphoma (LGITL). Although changes in intestinal microbiota and fecal metabolites have been reported in dogs and humans with chronic enteropathy, research in cats has been limited. Therefore, this study aimed to evaluate the fecal microbiota and lipid-related fecal metabolites in cats with FCE to a clinically healthy comparison group (CG). A total of 34 cats with FCE (13 FRE, 15 IBD, and 6 LGITL) and 27 cats in the CG were enrolled in this study. The fecal microbiota was evaluated by the qPCR-based feline Dysbiosis Index (DI). The feline DI in cats with CE (median: 1.3, range: -2.4 to 3.8) was significantly higher (p < 0.0001) compared to CG (median: - 2.3, Range: -4.3 to 2.3), with no difference found among the FCE subgroups. The fecal abundances of Faecalibacterium (p < 0.0001), Bacteroides (p < 0.0001), Fusobacterium (p = 0.0398), Bifidobacterium (p = 0.0004), and total bacteria (p = 0.0337) significantly decreased in cats with FCE. Twenty-seven targeted metabolites were measured by gas chromatography-mass spectrometry, including long-chain fatty acids (LCFAs), sterols, and bile acids (BAs). Fecal concentrations of 5 of 12 LCFAs were significantly increased in cats with FCE compared to CG. Fecal concentrations of zoosterol (p = 0.0109), such as cholesterol (p < 0.001) were also significantly increased in cats with FCE, but those of phytosterols were significantly decreased in this group. No differences in fecal BAs were found between the groups. Although no differences were found between the four groups, the fecal metabolomic pattern of cats with FRE was more similar to that of the CG than to those with IBD or LGITL. This could be explained by the mild changes associated with FRE compared to IBD and LGITL. The study showed changes in intestinal microbiota and alteration of fecal metabolites in FCE cats compared to the CG. Changes in fecal lipids metabolites suggest a dysmetabolism of lipids, including LCFAs, sterols, and unconjugated BAs in cats with CE.

Persistence and Sexual Dimorphism of Gut Dysbiosis and Pathobiome after Sepsis and Trauma.

To evaluate the persistence of intestinal microbiome dysbiosis and gut-plasma metabolomic perturbations following severe trauma or sepsis weeks after admission in patients experiencing chronic critical illness (CCI). Trauma and sepsis can lead to gut dysbiosis and alterations in the plasma and fecal metabolome. However, the impact of these perturbations and correlations between gut dysbiosis and the plasma metabolome in chronic critical illness have not been studied. A prospective observational cohort study was performed with healthy subjects, severe trauma patients, and patients with sepsis residing in an intensive care unit for 2 to 3 weeks. A high-throughput multi-omics approach was utilized to evaluate the gut microbial and gut-plasma metabolite responses in critically ill trauma and sepsis patients 14 to 21 days after intensive care unit admission. Patients in the sepsis and trauma cohorts demonstrated strikingly depleted gut microbiome diversity, with significant alterations and specific pathobiome patterns in the microbiota composition compared to healthy subjects. Further subgroup analyses based on sex revealed resistance to changes in microbiome diversity among female trauma patients compared to healthy counterparts. Sex--specific changes in fecal metabolites were also observed after trauma and sepsis, while plasma metabolite changes were similar in both males and females. Dysbiosis induced by trauma and sepsis persists up to 14 to 21 days after onset and is sex-specific, underscoring the implication of pathobiome and entero-septic microbial-metabolite perturbations in post-sepsis and posttrauma chronic critical illness. This indicates resilience to infection or injury in females' microbiome and should inform and facilitate future precision/personalized medicine strategies in the intensive care unit.

Experimental and computational investigation of the kinetic evolution of the glutaminolysis pathway and its interplay with the glycolysis pathway.

Exploring cellular responses necessitates studying real-time metabolic pathway kinetics, considering the adaptable nature of cells. Glycolysis and glutaminolysis are interconnected pathways fundamental to driving cellular metabolism, generating both energy and essential biosynthetic molecules. While prior studies explored glycolysis tracking, this research focuses on monitoring the kinetics of the glutaminolysis pathway by evaluating the effect of glutamine availability on glycolytic kinetics and by investigating the impact of a stimulator (oligomycin) and inhibitor (2DG) on the glycolytic flux in the presence of glutamine. Additionally, we adapted a rate equation model to provide improved understanding of the pathway kinetics. The experimental and simulated results indicate a significant reduction in extracellular lactate production in the presence of glutamine, reflecting a shift from glycolysis towards oxidative phosphorylation, due to the additional contribution of glutamine to energy production through the ETC (electron transport chain), reducing the glycolytic load. Oligomycin, an ETC inhibitor, increases lactate production to the original glycolytic level, despite the presence of glutamine. Nevertheless, its mechanism is influenced by the presence of glutamine, as predicted by the model. Conversely, 2DG notably reduces lactate production, affirming its glycolytic origin. The gradual increase in lactate production under the influence of 2DG implies increased activation of glutaminolysis as an alternative energy source. The model also simulates the varying metabolic responses under varying carbon/modulator concentrations. In conclusion, the kinetic model described here contributes to the understanding of changes in intracellular metabolites and their interrelationships in a way which would be challenging to obtain solely through kinetic assays.

Analysis of heaping-induced decline in olive quality: insights from integrated analysis between phenotypic traits and gene expression profiles.

Heaping is an unavoidable process before olive milling, and its duration significantly affects the olive quality. However, there is limited research on the quality changes of olive fruits on a short-time scale. To gain a better understanding of the molecular mechanisms underlying postharvest deterioration of olives, this study piled olives at room temperature and extracted oil at 0, 8, 24, 48 and 72h to analyze oil quality parameters. Gas/Liquid Chromatography-Mass Spectrometry (GC/LC-MS) techniques were employed to investigate variations in metabolite contents. Concurrently, the transcriptional profiles of olives during heaping were examined. As piling time progressed, quality indicators declined, and stored fruit were categorized into three groups based on their quality characters: '0h' belongs to the first category, '8h' and '24h' to the second category, and '48h' and '72h' to the third category. Metabolite changes were consistent with the expression patterns of genes related to their synthesis pathways. Additionally, ethylene was identified as a crucial factor influencing fruit senescence. These findings establish a foundation for further research on olive deterioration after harvesting and offer insights for optimizing olive oil production.

Changes in gut microbiota and metabolites of mice with intravenous graphene oxide-induced embryo toxicity.

The online version contains supplementary material available at 10.1007/s43188-024-00242-3.

Armillariella tabescens-derived polysaccharides alleviated Ɒ-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Dynamic Interplay between Microbiota Shifts and Differential Metabolites during Dairy Processing and Storage.

Due to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk's initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively.

Characteristics of the gut microbiota and serum metabolites in postmenopausal women with reduced bone mineral density.

Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.

Investigating the proliferative inhibition of HepG2 cells by exosome-like nanovesicles derived from Centella asiatica extract through metabolomics

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

Transcriptomics and metabolomics of the molecular mechanisms of ginseng's response to the continuous cropping obstacle

Ginseng is a plant with a long history of use in traditional Chinese medicine. However, large-scale cultivation of ginseng is limited by widespread issues with continuous cropping. To explore the physiological and molecular mechanisms behind ginseng crop disorders, transcriptomics and metabolomics were combined in this study to analyze the effects of continuous cropping on changes in ginseng metabolites, differential gene expression, and regulation of root secretions. The results showed that 106 metabolites and 1175 genes were significantly altered at the metabolic and transcriptional levels in ginseng from continuous cropping compared with the control group. More organic acids, alkaloids, flavonoids, and phenolics accumulated in the ginseng from continuous cropping than the control ginseng. Furthermore, significant differences were found in the expression of genes involved in phytohormone signaling, phenylpropanoid biosynthesis, and plant–pathogen interaction pathways. The results provide information on the regulation of expression of genes associated with continuous cropping disorders, and suggest that continuous cropping disorders may lead to severe damage to ginseng roots by pathogens and result in slow growth. Our research provides new insight into the response of ginseng to crop disorders, and reveals potential molecular mechanisms of the ginseng response to crop disorders.

Phenolic metabolites changes during baijiu fermentation through non-targeted metabonomic

To investigate the changes of phenolic metabolite during different grains fermentation stages of Chinse Baijiu, the ultra-performance liquid chromatography-quadrupole time of-flight mass spectrometry (UHPLC-QTOF-MS) was applied to identify and analyze the different phenolic metabolites, combined with principal component analysis and partial least squares discriminant analysis. Results indicated that significant differences in phenolic metabolites during different fermentation stages were found. Among the 231 phenolic metabolites detected, 36, 31, 19, 23, 14, and 50 differential phenolic metabolites were screened between different groups using partial least squares discriminant analysis. Twelve metabolic pathways with high correlation of differential phenolic metabolites and 23 main participating differential metabolites were identified through KEGG metabolic pathway enrichment analysis. The present study preliminarily revealed the differences of phenolic metabolites at different fermentation stages, and providing a theoretical basis for the further improving of the taste and quality of Chinese Baijiu.

Metabolomics-based study on the significance of differential metabolite binding IgG isoforms in Hemolytic disease of newborn

ABSTRACT Background: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. Methods: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. Results: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. Conclusion: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia

Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998–1999 (mean age = 75.2 ± 2.9 years old, 37.8% Black, 50% women) from the Health, Aging and Body Composition study. Dementia diagnosis was determined by race-specific decline in 3MS scores, medication use, and hospital records through 2014. Cognition and mobility were repeatedly measured using 3MS and a 20-m walking test up to 10 years, respectively. We examined metabolite associations with changes in 3MS (n = 2046) and gait speed (n = 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted p < 0.05). Twenty-six metabolites were associated with both cognitive and gait declines. Eighteen of 26 metabolites were associated with dementia risk (p < 0.05), notably amino acids, glycerophospholipids (lysoPCs, PCs, PEs), and sphingolipids. Results remained similar after adjusting for cardiovascular disease or apolipoprotein E ɛ4 carrier status. During aging, metabolomic profiles of cognitive decline and mobility decline show distinct and shared signatures. Shared metabolomic profiles suggest that inflammation and deficits in mitochondria and the urea cycle in addition to the central nervous system may play key roles in both cognitive and mobility declines and predict dementia. Future studies are warranted to investigate longitudinal metabolite changes and metabolomic markers with dementia pathologies.

Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters.

Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD. Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD. The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups. This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.

Changes in various secondary metabolites by crossing modern rose cultivars

ABSTRACT The aim of the study was to determine the content and composition of phenolic compounds in autochthonous rose hips (R. pendulina, R. spinosissima and R. gallica) and to compare them with the content of phenolic compounds in their cultivars (‘Harstad’, ‘Bourgogne’, ‘Mount Everest’, ‘Poppius’, ‘Frühlingsduft’, ‘Single Cherry’, ‘Frühlingsmorgen’, ‘ Violacea’ and ‘Splendens’) collected in Arboretum Volčji Potok in Slovenia. The total content of phenolic compounds in the flesh with skin was lowest in ‘Mount Everest’ (3603.57 mg · kg−1 f.w.), which is derived from R. pendulina, and highest in ‘Splendens’ (68789.39 mg · g−1 f.w.), which is derived from R. gallica. In seeds, the phenolic compound content was lower, as expected, ranging from 757.02 mg · kg−1 f.w. (‘Mount Everest’) to 6823.21 mg · kg−1 f.w. (‘Single Cherry’). It can be concluded that the cultivars differ significantly from each other due to the content of different bioactive compounds. Based on the obtained results, we cannot determine to which basic rose plant the cultivar belongs based only on the content of one analysed compound. The contents were very different because only one parent plant is known for a given cultivar and breeding programmes in roses were very narrowly focussed on specific targets.

Glucose metabolism partially regulates β-cell function through epigenomic changes.

The β-cell relies predominantly on glucose utilization to generate adenosine triphosphate, which is crucial for both cell viability and insulin secretion. The β-cell has evolved remarkable metabolic flexibility to productively respond to shifts in environmental conditions and changes in glucose availability. Although these adaptive responses are important for maintaining optimal cellular function, there is emerging evidence that the resulting changes in cellular metabolites can impact the epigenome, causing transient and lasting alterations in gene expression. This review explores the intricate interplay between metabolism and the epigenome, providing valuable insights into the molecular mechanisms leading to β-cell dysfunction in diabetes. Understanding these mechanisms will be critical for developing targeted therapeutic strategies to preserve and enhance β-cell function, offering potential avenues for interventions to improve glycemic control in individuals with diabetes.