Metabolites[JOURNAL]
Sun
200 papers
Comparative Metabolomic Analysis of Different Organs of Understory-Transplanted and Wild .
Shen J, Chen Y, Zhang H … +1 more , Hu T
Metabolites · 2026 May · PMID 42346334 · Full text
: The artificial cultivation of under forest understory conditions offers a sustainable alternative to wild harvesting, yet the metabolic adaptations underlying transplantation stress and recovery remain poorly understo...
: The artificial cultivation of under forest understory conditions offers a sustainable alternative to wild harvesting, yet the metabolic adaptations underlying transplantation stress and recovery remain poorly understood. Objectives: In this study, we performed a comparative metabolomics analysis of different organs (leaves, current-year stems, three-year-old stems, and roots) from wild plants and those transplanted to the understory. and : Metabolite annotation and classification revealed that over 60% of the metabolites fell into the categories of lipids and lipid-like molecules, organoheterocyclic compounds, phenylpropanoids, and polyketides. Further differential analysis of metabolites showed that understory transplantation significantly altered the metabolic profiles of all organs, exhibiting organ-specific response patterns. For the metabolite components in the organs of transplanted and wild , these metabolites were mainly classified into eight categories: alkaloids and derivatives; benzenoids; lignans, neolignans and related compounds; lipids and lipid-like molecules; organic acids and derivatives; organoheterocyclic compounds; phenylpropanoids and polyketides; and organic oxygen compounds. Notably, the contents of (-)-asarinin, (Z)-1-(methylthio)-5-phenyl-1-penten-3-yne, and stearidonic acid (SDA, 18:4n-3) were higher in transplanted plants than in wild plants, indicating the potential of understory cultivation for the targeted extraction of these bioactive compounds. : These findings provide a metabolomics basis for optimizing the artificial cultivation and quality control of . This study highlights the value of metabolomics in understanding the metabolic composition of and offers a reference for its artificial cultivation.
Geographic Variation and Quality Consistency of Toddaliae Asiaticae Radix: A Hybrid Framework Integrating Environmental Feature and Bioactivity-Weighted Modeling.
Wei L, Chen H, Sun M … +3 more , Song Y, Zhang C, Zhou Z
Metabolites · 2026 May · PMID 42346333 · Full text
: Toddaliae Asiaticae Radix (TA) boasts a long history of medicinal application. However, origin traceability and quality assessment of the widely distributed original plant have not been fully elucidated. : A hybrid fr...
: Toddaliae Asiaticae Radix (TA) boasts a long history of medicinal application. However, origin traceability and quality assessment of the widely distributed original plant have not been fully elucidated. : A hybrid framework integrating targeted metabolomics, network pharmacology (NP), and machine learning (ML) was established. By optimizing key parameters, a high-coverage and rapid method for multiple categories compounds was developed using ultra-high performance liquid chromatography-multiple reaction monitoring tandem mass spectrometry (UPLC-MRM MS/MS). Using samples collected across 16 geographical regions, redundancy analysis (RDA) and pattern recognition techniques were applied to explore environment-sensitive metabolites. Taking into account five types of diseases, NP analysis was employed to obtain the bioactive components and their contribution weight in disease treatment. Subsequently, core Quality Markers (Q-Markers) with dual functions of responsive to geographic variations and biologically relevant to therapeutic efficacy were figured out, and were used to establish origin scoring model and discrimination model. : The geographical metabolic characteristics of the TA from broad regions in China were thoroughly analyzed, and 60 geographically sensitive compounds were identified. Through NP analysis, 27 core Q-Markers were locked. The bioactivity-weighted scoring model based on Q-Markers revealed the consistency of regional rankings as well as minor fluctuations across five diseases. ML demonstrated that the Q-Markers preserved regional discrimination performance, and the introducing of practical-oriented weights enhanced overall discriminative confidence. : This research decodes the Geographical metabolic characteristics of TA, and highlights the necessity of function-oriented prioritization of drug resources.
Effects of Long-Term Administration of Ginsenosides on the Structure of Intestinal Microflora and the Absorption and Utilization of Saponins in Rats.
Dou G, Bi X, Wang N … +7 more , Li S, Huang Y, Lu S, Wang Z, Ji W, Hong Y, Dong W
Metabolites · 2026 May · PMID 42346332 · Full text
Ginsenosides are active natural compounds with diverse effects, and their interaction with the gut microbiota can influence microbial composition and abundance, though the long-term effects remain unclear. This study ex...
Ginsenosides are active natural compounds with diverse effects, and their interaction with the gut microbiota can influence microbial composition and abundance, though the long-term effects remain unclear. This study examines the impact of long-term oral ginsenoside administration on gut microbiota composition and structure in rats, as well as its pharmacokinetics. Twenty healthy male Wistar rats were divided into a control group (CK, receiving distilled water) and a ginsenoside treatment group (PGE, 100 mg/kg) for 30 days. Fecal samples were analyzed using 16S rRNA high-throughput sequencing on the Illumina HiSeq platform to assess microbial diversity. Concurrently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to determine the concentrations of ginsenosides in the serum and to investigate their pharmacokinetic properties ( < 0.05). The results indicated that the α-diversity indices of the gut microbiota in the PGE group were significantly higher than in the CK group, suggesting that ginsenosides enhance microbial richness and diversity ( < 0.05). At the phylum level, the relative abundance of in the PGE group increased by 10.6% ± 2.72%, while that of decreased by 11.5% ± 3.18%; at the genus level, the proportion of genus rose by 17.78% ± 4.37% ( < 0.05). Pharmacokinetic analysis revealed that the area under the concentration-time curve (AUC) and maximum concentration (C) of ginsenosides were significantly higher in the PGE group than in the CK group. Chronic oral administration of ginsenosides improves their absorption and utilization through gut microbiota modulation, offering experimental evidence for deeper insight into ginsenoside-microbe interactions.
GC-MS-Based Comparative Analysis of Compounds in Host Plants and Insect Gut Extracts.
Dill R, Smith K, Okoth S … +2 more , Cheseto X, Osano A
Metabolites · 2026 May · PMID 42346331 · Full text
: Herbivorous insects feed on plant tissues to obtain nutrients necessary for growth and development while simultaneously ingesting diverse plant secondary metabolites. Understanding the fate of these compounds during di...
: Herbivorous insects feed on plant tissues to obtain nutrients necessary for growth and development while simultaneously ingesting diverse plant secondary metabolites. Understanding the fate of these compounds during digestion is important for advancing knowledge of insect nutritional physiology and diet-associated biochemical processes. This study aimed to comparatively profile metabolites in host plants and corresponding insect gut extracts to generate insights into compound transfer and compositional changes within these systems. : Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics was combined with Ultraviolet-Visible (UV-Vis) quantification of total phenols and flavonoids to compare host plant tissues and insect gut extracts in three systems: fall armyworm () larvae on maize (), desert locust () on wheatgrass (), and silkworm () on mulberry (). The analytical approach targeted semi-volatile and moderate polar compounds within the constraints of the extraction and detection workflow. : UV-Vis analysis revealed consistent enrichment of total phenols in insect guts relative to host plants (1.4- to 0.35-fold), while flavonoids were reduced (2- to 7-fold). GC-MS analyses showed clear separation of gut and plant metabolomes, with <35% shared metabolites and the majority unique to insect guts. Insect extracts were enriched in hydrocarbons, fatty acids, sterols, and terpenoid derivatives, reflecting extensive biochemical transformation. Sex-specific metabolite differences were observed in silkworm and desert locust guts despite identical diets. These findings show differences between plant and gut metabolite profiles, reflecting selective enrichment, depletion, and restructuring of dietary compounds during digestion. Overall, this study provides comparative metabolic data on insect-plant feeding systems and highlights the gut as a dynamic environment associated with changes in dietary metabolite composition. These findings contribute to understanding how plant-derived compounds are represented in insect gut extracts and establish a baseline framework for future studies investigating the biochemical processes underlying insect digestion and nutrient utilization.
Fish Nutrition and Metabolism: From Intestinal Microbiota to Metabolic Homeostasis.
Wang L, Tan P, Zuo R
Metabolites · 2026 May · PMID 42346330 · Full text
Aquaculture continues to be a crucial sector for global food security [...].
Aquaculture continues to be a crucial sector for global food security [...].
Brown Adipocyte Promotes HR+ Breast Cancer Invasiveness Through IRX3-Mediated Mitochondrial Dysfunction.
Hu S, Hu B, Su S … +5 more , Zhou Y, Liu G, Gao Y, Ni Q, Hou J
Metabolites · 2026 May · PMID 42346329 · Full text
Adipocytes play a critical role in the breast cancer tumorigenic microenvironment. However, their effects and underlying mechanisms remain unclear. This study aims to investigate the role of adipocytes in luminal A breas...
Adipocytes play a critical role in the breast cancer tumorigenic microenvironment. However, their effects and underlying mechanisms remain unclear. This study aims to investigate the role of adipocytes in luminal A breast cancer invasiveness at the cellular and molecular levels. Various adipocyte types were co-cultured with MCF7 breast cancer cells in direct and indirect manners. Invasiveness was assessed via proliferation, migration, and invasion, with alterations examined at morphological, cellular, and molecular levels. The role of adipocytes on MCF7 was further explored using an orthotopic breast cancer xenograft mouse model. MCF7 co-cultured with adipocytes, especially brown adipocytes (BAC), showed increased invasiveness and tumorigenic potential. Morphologically, co-cultivation with BAC increased the proliferation, EMT, and stemness of MCF7. Mechanistically, co-culture of MCF7 with BAC exhibited disturbed expression of genes related to adipogenesis and mitochondrial dynamics; notably, IRX3 was the most prominently elevated one. Knockdown of IRX3 restored balanced mitochondrial function and reduced both the invasiveness of breast cancer cells in vitro and tumor growth in vivo. Brown adipocytes promote breast cancer invasiveness by upregulating adipogenesis-related IRX3, which acts via the mitochondrial functional regulation.
Benchmarking Spatial Clustering Methods for Mass Spectrometry-Based Spatial Metabolomics.
Lu Y, Mei Z, Deng H … +3 more , Zhao Y, Feng C, Liu S
Metabolites · 2026 May · PMID 42188057 · Full text
Mass spectrometry imaging (MSI) enables in situ mapping of metabolite distributions within tissues, and spatial clustering is a key step for delineating metabolically distinct regions. Nevertheless, spatial clustering me...
Mass spectrometry imaging (MSI) enables in situ mapping of metabolite distributions within tissues, and spatial clustering is a key step for delineating metabolically distinct regions. Nevertheless, spatial clustering methods have not been systematically benchmarked for spatial metabolomics data. : Here, we evaluated the effects of ion filtering and clustering method selection on clustering performance and established a dual-metric framework that jointly assesses the spatial continuity of cluster labels and inter-cluster metabolic heterogeneity. We benchmarked 30 clustering algorithms across 12 heterogeneous MSI datasets spanning three major ion sources, four mass analyzers, and multiple spatial resolutions, covering approaches from non-spatial methods to advanced spatially aware models. : Noise filtering markedly improved the spatial continuity of results generated by non-spatial methods (mean improvement, approximately 28%) but provided limited benefit for spatially aware methods. Across the 12 datasets, a median of only 11 methods satisfied both evaluation criteria simultaneously, whereas SSC and DRSC met the dual-metric thresholds in at least nine datasets. In the mbrain2_pos50 dataset, the top-ranked method based on the composite dual-metric score achieved 22% higher concordance between cluster assignments and cell-type annotations than the lowest-ranked method. : Together, the proposed evaluation framework and the online platform SMcluster provide a standardized resource for benchmarking and selecting MSI clustering methods. Our results highlight the critical roles of preprocessing and method selection in determining spatial clustering performance and offer practical guidance for spatial metabolomics studies.
Obesity, Low-Grade Chronic Inflammation, and Clinical Outcomes in Spondyloarthritis: A Translational Synthesis.
Belančić A, Radić M, Rogoznica Pavlović M … +5 more , Vučković M, Prižmić PŠ, Gkrinia EMM, Radić J, Fajkić A
Metabolites · 2026 May · PMID 42188056 · Full text
This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue...
This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis-the primary pathological site in SpA-potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal-immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose-response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes.
Establishment of Three Different Glycation-Damage Cell Models and Analysis of Their Action Mechanism.
Qian X, Cao C, Liu L
Metabolites · 2026 May · PMID 42188055 · Full text
With rising per capita sugar consumption, skin glycation-related issues including dullness, homeostasis disruption and accelerated wrinkling have gained widespread attention. However, globally standardized and rigorous e...
With rising per capita sugar consumption, skin glycation-related issues including dullness, homeostasis disruption and accelerated wrinkling have gained widespread attention. However, globally standardized and rigorous evaluation criteria for anti-glycation efficacy remain lacking. This study aimed to establish stage-specific glycation injury cell models and elucidate the stage-dependent molecular mechanisms of glycation-induced fibroblast damage, providing a standardized reference for anti-glycation efficacy assessment. Three glycation injury models were constructed in human foreskin fibroblasts (HFF-1): early-stage (glucose-induced), intermediate-stage (glyoxal-induced), and late-stage (advanced glycation end products (AGEs)-induced). Core biomarkers including Nε-(carboxymethyl)lysine (CML), collagen type I (Col I) and elastin (ELN) were used to optimize modeling conditions via Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). Untargeted metabolomics based on ultra-high-performance liquid chromatography (UHPLC)-Q Exactive Orbitrap was applied to identify differential metabolites and perturbed pathways, following Metabolomics Standards Initiative (MSI) Level 2 identification criteria. Optimal conditions were determined as 50 mmol/L glucose for 48 h, 0.5 mmol/L glyoxal for 48 h, and 200 μg/mL AGEs for 24 h. A total of 319, 34 and 148 differential metabolites were identified in the three groups, respectively. Six key pathways were significantly perturbed. Early and intermediate models shared similar mechanisms (purine metabolism disturbance), while the late model showed distinct alterations in pyrimidine, nicotinate, arachidonic acid and steroid hormone metabolism. Three stable stage-specific glycation models were successfully established in HFF-1 cells. Significant differences in metabolic profiles and mechanisms exist across the three stages, providing a rational basis for model selection and theoretical support for anti-glycation efficacy evaluation.
Iodoacetamine-Alkyne Derivatization-Based Liquid Chromatography-Mass Spectrometry Method for Quantification of Thiol Metabolites in Serum Samples of Hepatocellular Carcinoma Patients.
Mei C, Wu XZ, Xiao HM … +4 more , Temerdashev A, An N, Zhu QF, Feng YQ
Metabolites · 2026 May · PMID 42188054 · Full text
: The dysregulation of thiol metabolites is strongly linked to hepatocellular carcinoma (HCC) pathogenesis. However, quantifying these highly polar and oxidation-prone thiols in clinical serum samples via conventional li...
: The dysregulation of thiol metabolites is strongly linked to hepatocellular carcinoma (HCC) pathogenesis. However, quantifying these highly polar and oxidation-prone thiols in clinical serum samples via conventional liquid chromatography-mass spectrometry (LC-MS) remains challenging due to their poor sensitivity and reproducibility. : We developed a sensitive and robust iodoacetamine-alkyne (IAM) derivatization-based LC-MS method for quantification of seven trans-sulfuration pathway thiols in human serum. : IAM derivatization markedly improved the method's specificity due to enhanced chromatographic retention and diagnostic MS/MS fragments containing both the alkyne tag and analyte backbone. Sensitivity increased 33-to-160-fold versus underivatized analytes, with limits of detection of 0.02-0.1 nM. All analytes exhibited good linearity, acceptable precision with intra-day and inter-day relative standard deviations in the range of 1.2-13.8%, and high recovery from 88.6% to 102.9%. : From the thiol quantification in human serum from 40 HCC patients and 40 healthy controls, it was found that levels of cysteine, homocysteine, glutathione, and cysteinylglycine were significantly lower in HCC patients ( < 0.05). A two-variable logistic regression model using cysteine and cysteinylglycine achieved 90.0% specificity and 80.0% sensitivity for robust HCC discrimination between HCC patients and healthy controls to some extent, with an area under the receiver operating characteristic curve of 0.88 (95% confidence interval: 0.792-0.968).
Integrated Redox Profiling: Simultaneous Determination of Ubiquinol-10, Ubiquinone-10, and Alpha-Lipoic Acid in Serum by LC-MS/MS.
Gallou D, Begou O, Theodoridis G … +1 more , Gika H
Metabolites · 2026 May · PMID 42188053 · Full text
: Coenzyme Q and Alpha-lipoic acid are two essential antioxidants involved in numerous physiological processes, including cellular energy production and the mitigation of oxidative stress. Their accurate quantification i...
: Coenzyme Q and Alpha-lipoic acid are two essential antioxidants involved in numerous physiological processes, including cellular energy production and the mitigation of oxidative stress. Their accurate quantification is critical for understanding their biological roles and therapeutic potential. Herein, an RPLC-MS/MS method for the rapid and simultaneous determination of ubiquinone-10 (CoQ), the reduced form ubiquinol-10 (CoQH), and Alpha-lipoic acid (ALA) in human serum was developed and validated. : Chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 150 mm, i.d. 1.7 μm). Detection was performed on a SCIEX Triple Quad 6500+ system, applying multiple reaction monitoring (MRM). Single-phase protein precipitation was selected as the sample preparation protocol, providing satisfactory recovery for the analytes. : The method was linear over the concentration of 53.8-613 ng/mL for CoQH, 23.1-263 ng/mL for CoQ and 7.7-87.6 ng/mL for ALA. Intra- and inter-day accuracy was found to be between 81.8 and 109% and 84.4 to 106%, respectively, for all analytes, while intra- and inter-day precision was found to vary from 0.8% to 9.9% %RSD and 2.0% to 7.7% %RSD, respectively. A limit of quantitation (LOQ) of 4.2 ng/mL was found for CoQH, 1.7 ng/mL for CoQ and 0.7 ng/mL for ALA. : The developed LC-MS/MS method enables rapid, sensitive and simultaneous quantification of CoQH, CoQ and ALA in human serum with satisfactory accuracy, precision and sensitivity. The method is suitable for bioanalytical applications and was successfully applied to the analysis of 10 real samples obtained from healthy volunteers.
Metabolomic Signature of Visceral Adiposity: Insights from a Population-Based Cohort.
Naja K, Anwardeen N, Almuraikhy S … +2 more , Elrayess MA, Malki A
Metabolites · 2026 May · PMID 42188052 · Full text
Visceral adipose tissue (VAT) is a key determinant of cardiometabolic risk, yet its underlying molecular mechanisms remain incompletely characterized. Metabolomics offers an opportunity to identify circulating biomarkers...
Visceral adipose tissue (VAT) is a key determinant of cardiometabolic risk, yet its underlying molecular mechanisms remain incompletely characterized. Metabolomics offers an opportunity to identify circulating biomarkers that capture VAT-related biology beyond conventional clinical measures. : We conducted a cross-sectional analysis of 2526 participants from the Qatar Biobank using untargeted serum metabolomics profiling. VAT was quantified using DXA-derived estimates and analyzed both as a continuous variable and by comparing individuals in the highest quartile to the remainder quartiles. Associations between metabolites and VAT were assessed using multivariate partial least squares discriminant analysis and adjusted linear regression models controlling for age, sex, and BMI, with Bonferroni correction for multiple testing. : Continuous VAT was associated with 106 metabolites, while the Q4 versus Q1-Q3 contrast identified 23 metabolites, with overlapping metabolites defining a robust core VAT signature. Higher VAT was characterized by coordinated elevation of branched-chain amino acids and their keto/hydroxy acid derivatives, glutamate, and central carbon intermediates, consistent with impaired mitochondrial oxidative decarboxylation. We further identified 4-hydroxyglutamate as a novel collagen-derived metabolite positively associated with VAT, suggesting a potential link between extracellular matrix remodeling and glutamate-centered metabolism. Additionally, greater VAT was associated with lower concentrations of glycine and glycine conjugates and reduced levels of unsaturated sphingomyelins and plasmalogens. : These findings provide potential mechanistic insights into VAT-related metabolic dysfunction and identify candidate circulating biomarkers that may enable non-invasive assessment of visceral fat-associated cardiometabolic risk. Longitudinal and mechanistic studies are warranted to establish causality and clinical utility.
TCM-Derived Natural Compounds Targeting the Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease: Gut-Liver Axis Mechanisms, Safety Considerations, and Translational Challenges.
Deng H, Zhang R
Metabolites · 2026 May · PMID 42188051 · Full text
The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to thei...
The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising application prospects in the prevention and treatment of MASLD. However, basic research on their toxicity still lags behind, and issues related to safety and clinical translation urgently need attention. This article systematically reviews the research progress on how flavonoids, triterpenoids, alkaloids, and polysaccharides improve hepatic steatosis, inflammatory responses, and metabolic disorders from a toxicological perspective by reshaping the intestinal microbiota, repairing the intestinal mucosal barrier, regulating short-chain fatty acid and bile acid metabolism, and synergistically acting on signaling pathways such as TLR4/NF-kB, FXR, TGR5, SIRT1, and the NLRP3 inflammasome. Furthermore, by combining methods such as 16S rRNA sequencing, metagenomics, metabolomics, and multi-omics integration, the article analyzes their application value and limitations in toxicological mechanism research, and discusses the translational bottlenecks faced by Chinese herbal monomers in pharmacokinetics, bioavailability, quality standardization, targeted delivery, and toxicological safety. Existing evidence indicates that Chinese herbal monomers have a three-in-one intervention advantage of microecological remodeling-metabolic regulation-inflammation inhibition, but their long-term medication safety, toxic target organs, dose-effect/toxicity relationships, and potential drug interactions still need further clarification. This article aims to provide a systematic reference for the safety evaluation and clinical translational research of Chinese herbal monomers in the prevention and treatment of MASLD.
The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review.
Zubrzycki M, Kuśmierczyk M, Gummert JF … +6 more , Costard-Jäckle A, Paluszkiewicz L, Hecht T, Birschmann I, Zubrzycka A, Zubrzycka M
Metabolites · 2026 May · PMID 42188050 · Full text
Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described...
Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management.
Pyrroloquinoline Quinone Mitigates Type 2 Diabetes-Induced Cardiac Injury Through Mitochondrial Quality Control and Inhibition of NLRP3-Dependent Pyroptosis.
Zhang X, Liu W, Fu Z … +8 more , Chen Z, Chen Q, Shen Y, Jin Y, Xu D, Wang Y, Qu X, Zhang Y
Metabolites · 2026 May · PMID 42188049 · Full text
: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in dia...
: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in diabetic cardiomyopathy (DCM) induced by Type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood. : A T2DM mouse model was established via a high-fat diet and low-dose STZ. We investigated the cardioprotective effects of 12-week oral PQQ administration, assessing fasting blood glucose, oral glucose tolerance, cardiac function, myocardial histopathology, blood biochemistry, mitophagy, and NLRP3 inflammasome activation. In vitro experiments using AC16 cardiomyocytes exposed to palmitic acid and high glucose were also conducted. : Results showed PQQ significantly improved cardiac function, attenuated remodeling, and reduced proinflammatory cytokines in mice with T2DM, regulated key mitophagy-related proteins (Parkin, Beclin-1, LC3B-II, p62), and downregulated NLRP3 inflammasome pathway components (Caspase-1, NLRP3, IL-1β, IL-18). In vitro experiments demonstrated that PQQ reduced reactive oxygen species (ROS) production, improved mitochondrial membrane potential, promoted mitophagy, and inhibited NLRP3 inflammasome-mediated pyroptosis. : PQQ alleviates DCM in mice with T2DM by improving mitochondrial quality control, promoting mitophagy, and subsequently inhibiting NLRP3 inflammasome-mediated pyroptosis, highlighting its potential as a promising therapeutic agent for T2DM-associated cardiomyopathy.
Polysaccharide from Seed Endosperm Ameliorates Type 2 Diabetes and Its Associated Cardiorenal Injuries by Modulating TLR4/MyD88/NF-κB Pathway and Gut Microbiota.
Liu M, Liao W, Liu H … +4 more , Xu F, Zhang Y, Wang X, Wu H
Metabolites · 2026 May · PMID 42188048 · Full text
BACKGROUND: Type 2 diabetes mellitus (T2DM) represents a pressing global health challenge, underscoring the urgency of developing effective dietary interventions derived from natural resources. Zaojiaomi polysaccharide (...
BACKGROUND: Type 2 diabetes mellitus (T2DM) represents a pressing global health challenge, underscoring the urgency of developing effective dietary interventions derived from natural resources. Zaojiaomi polysaccharide (ZJMP) from the endosperm of seeds (zaojiaomi), a traditional edible product, exhibits largely underexplored potential in T2DM management. METHODS: In the present study, the antidiabetic effects and underlying mechanisms of ZJMP were investigated using a rat model of T2DM induced by a high-fat diet (HFD) combined with streptozotocin (STZ). Relevant biochemical indicators were detected, and histopathological examination was performed. The expression levels of key components of the TLR4/MyD88/NF-κB signaling pathway, as well as the inflammatory cytokines IL-6 and IL-1β in renal tissues, were further analyzed. Additionally, gut microbiota composition and the levels of short-chain fatty acids were determined. RESULTS: ZJMP treatment significantly ameliorated hyperglycemia and dyslipidemia, elevated serum insulin levels, reduced intestinal mucosal permeability, and attenuated histopathological lesions in the heart, kidney, and pancreas of T2DM rats. Meanwhile, ZJMP notably alleviated renal inflammation by suppressing the production of IL-1β and IL-6, as well as inhibiting the TLR4/MyD88/NF-κB pathway. Furthermore, ZJMP administration effectively modulated gut microbiota composition and increased fecal concentrations of acetic acid and propionic acid. CONCLUSIONS: Collectively, these findings elucidate the novel bioactivity of ZJMP and highlight its potential as a promising functional food ingredient or dietary supplement for T2DM management.
Targeting NAD Homeostasis: Compartmentalization, Quantification, and Modulation.
Nobile M, Fontanini V, Serrao S … +3 more , Burtscher J, Re F, Paglia G
Metabolites · 2026 May · PMID 42188047 · Full text
Nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are essential coenzymes that play central roles in cellular redox homeostasis, energy metabolism, DNA repair, and signaling. Cellular NAD levels are mai...
Nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are essential coenzymes that play central roles in cellular redox homeostasis, energy metabolism, DNA repair, and signaling. Cellular NAD levels are maintained by a dynamic balance between the de novo Preiss-Handler, and salvage synthesis pathways, and consumption by enzymes like sirtuins, PARPs, and CD38. Among these, the nicotinamide Phosphoribosyltransferase (NAMPT)-driven salvage pathway represents the predominant route of NAD+ synthesis. The specific regulation of NAD (NAD and NADH) levels across distinct subcellular compartments has emerged as a critical determinant of cellular function but it remains poorly understood. Dysregulation of NAD metabolism is a hallmark of aging and various pathologies, including cancer, neurodegenerative disorders, and metabolic diseases, making strategies to modulate NAD levels a promising therapeutic frontier. This review provides the first integrated overview of NAD concentrations across cellular compartments (cytosol, mitochondria, nucleus, endoplasmic reticulum, Golgi, peroxisomes, and the extracellular space) together with measurement and modulation strategies. We summarize current knowledge on NAD distribution within organelles, address key challenges in accurate quantification, and highlight established and emerging approaches for both global and compartment-specific analysis. Finally, we discuss therapeutic strategies, from NAD precursor supplementation to enzyme modulators and gene therapy, highlighting both their translational potential and current limitations in treating diverse diseases and prolonging life and health span.
Hypothesis of the Causal Mechanisms Between Gut Microbiota and Neurodegenerative Diseases: An Elucidation from Evolutionary Perspective and Metabolic Consideration.
Tang G, Guo L, Liu Z … +1 more , Quan Y
Metabolites · 2026 May · PMID 42188046 · Full text
Growing evidence links gut microbiota dysbiosis to neurodegenerative diseases (NDs) such as Alzheimer's disease and Parkinson's disease, yet the field remains dominated by correlational observations rather than experimen...
Growing evidence links gut microbiota dysbiosis to neurodegenerative diseases (NDs) such as Alzheimer's disease and Parkinson's disease, yet the field remains dominated by correlational observations rather than experimentally validated causal mechanisms. In this hypothesis-generating Perspective, we propose that causal inference in microbiota-associated neurodegeneration may be strengthened by combining two complementary lenses: evolutionary biomedicine and microbial metabolism. Because evolutionary information carries intrinsic temporal and causal structure, it can provide biological prior knowledge for inferring causal mechanisms of diseases. Human Accelerated Regions (HARs), genomic loci conserved across mammals but rapidly divergent in the human lineage, offer an anchor for identifying human-specific host-microbe co-evolutionary units relevant to NDs. We further hypothesize that microbial metabolites represent one class of mechanistically testable intermediates linking host genetic background, gut microbial ecology, and neurodegenerative phenotypes. This integrated evolutionary-metabolic perspective offers a tractable path from correlation toward mechanism in gut microbiota-ND research.
GDF15 Improves Renal Injury Induced by Ectopic Lipid Deposition via AMPK/SIRT1 Pathway-Mediated Autophagy.
Zhang Q, Yang X, Yang Y … +6 more , Wang M, Wu Y, Xie X, Jin Y, Yang M, Yang M
Metabolites · 2026 May · PMID 42188045 · Full text
OBJECTIVES: Obesity precipitates excessive lipid accumulation within the kidney, culminating in ectopic lipid deposition that compromises target organ function through lipotoxicity. Given the pivotal role of GDF15 in lip...
OBJECTIVES: Obesity precipitates excessive lipid accumulation within the kidney, culminating in ectopic lipid deposition that compromises target organ function through lipotoxicity. Given the pivotal role of GDF15 in lipid metabolism, this study aims to determine whether GDF15 can ameliorate ectopic lipid deposition and mitigate the resulting renal injury. METHODS: C57BL/6J mice were used to establish a high-fat diet-induced obesity model. Based on Lee's index, the mice were categorized into a diet-induced obesity group and an obesity-resistant group. Subsequently, the diet-induced obesity group received an injection of AAV-shGFRAL to knock down the GFRAL receptor. RESULTS: In obesity resistant mice, ectopic lipid deposition in the kidneys was markedly reduced, accompanied by decreased expression of the renal injury marker KIM-1 and significantly elevated levels of GDF15. Modulation of the GDF15-GFRAL axis demonstrated that reduced autophagy levels led to increased lipid accumulation and exacerbated renal injury. Conversely, GDF15 activates the AMPK/SIRT1 signaling pathway to promote cellular autophagy, thereby mitigating renal damage induced by ectopic lipid deposition. Consistent with this mechanism, the suppression of autophagy results in the aggravation of renal injury caused by ectopic lipid accumulation. CONCLUSIONS: GDF15 ameliorates renal injury induced by ectopic lipid deposition in the kidney primarily through activation of autophagy via the AMPK/SIRT1 signaling pathway.
The Effect of Angiotensin (1-7) on Serum Metabolomics in Obese Type 2 Diabetic Mice.
Chen Q, Sun M, Wang H … +1 more , Lu C
Metabolites · 2026 May · PMID 42188044 · Full text
: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. : Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with stre...
: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. : Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. : 1. Ang-(1-7) intervention decreased blood glucose ( < 0.05) and CRP levels ( < 0.01), and alleviated dyslipidemia ( < 0.05 or < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. : Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism.
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