Metabolites[JOURNAL]
Sun
200 papers
Targeting the Gut-Brain Axis: Protective Effects of NMN in Alleviating D-Galactose-Induced Cognitive Deficits.
Zang Z, Chen F, Tang Q … +4 more , Luo W, Lin Y, Li J, Yu Y
Metabolites · 2026 May · PMID 42188023 · Full text
: To evaluate the neuroprotective effect of nicotinamide mononucleotide (NMN), an NAD precursor, in a D-galactose-induced aging mouse model. Chronic D-galactose administration is widely used to establish age-related cogn...
: To evaluate the neuroprotective effect of nicotinamide mononucleotide (NMN), an NAD precursor, in a D-galactose-induced aging mouse model. Chronic D-galactose administration is widely used to establish age-related cognitive impairment driven by oxidative stress. : Mice received subcutaneous D-galactose for six weeks, concomitantly with oral NMN (300 or 500 mg/kg). Cognitive function was assessed using the Y-maze test and the Elevated Plus Maze test. Oxidative stress indicators, inflammatory cytokines, and Nrf2/HO-1 pathway components were measured by ELISA, Western blotting, and Immunohistochemistry. Gut microbiota composition was analyzed via 16S rRNA sequencing. : NMN supplementation improved spatial memory without affecting anxiety-related behavior. NMN enhanced the activities of antioxidant enzymes (SOD, GSH, CAT), reduced malondialdehyde and pro-inflammatory cytokine levels and decreased microglial activation in the hippocampus. Furthermore, NMN remodeled the gut microbiota by increasing butyrate-producing taxa (such as and ) and activated the Nrf2/HO-1 signaling pathway. : NMN alleviates age-related cognitive decline in mice by reducing oxidative stress, suppressing neuroinflammation, and modulating the gut microbiota. Targeting the gut-brain axis and the Nrf2/HO-1 pathway may therefore represent a promising therapeutic strategy for age-related neurodegeneration.
Physiology, Metabolomics, and Transcriptomics Reveal Effects of AMF and Co-Inoculation on Growth and Medicinal Compounds in .
Gong Y, Liu S, Zhao X … +6 more , Zhang W, Li J, Liu M, Zhang X, Jia H, Tang Z
Metabolites · 2026 May · PMID 42188022 · Full text
Microbial inoculants effectively alleviate inhibitory factors during plant cultivation; however, the effects and underlying mechanisms of arbuscular mycorrhizal fungi (AMF) and on the growth, metabolism, and bioactive c...
Microbial inoculants effectively alleviate inhibitory factors during plant cultivation; however, the effects and underlying mechanisms of arbuscular mycorrhizal fungi (AMF) and on the growth, metabolism, and bioactive compound production of are still poorly understood. : In this experiment, different concentrations of (10, 10, 10 spores/mL) (Q1, Q2, Q3), AMF, and their combined treatments (AQ1, AQ2, AQ3) were applied to seedlings via root irrigation, with an equal amount of sterile water as a control (CK). : The results showed that: (1) Under single inoculation with , root colonization rate increased with higher inoculation concentrations, reaching its peak at Q3. Additionally, AQ3 significantly enhanced AMF colonization in , and the presence of promoted AMF root colonization and expansion. (2) AQ3 significantly enhanced the growth and photosynthesis of , while also demonstrating excellent efficacy in alleviating lipid peroxidation-induced damage. (3) AQ3 treatment led to increased accumulation of major bioactive compounds in , including calycosin-7-glucoside, cycloastragenol, and astragalosides I-III. (4) AQ3 treatment significantly upregulated multiple key structural genes involved in phenylalanine metabolism and flavonoid biosynthesis pathways, including , , , and . : This upregulation enhanced the metabolic flux allocation from L-phenylalanine toward downstream flavonoid metabolites, thereby promoting the accumulation of major flavonoid constituents of , such as galangin and luteolin, in both roots and leaves.
Pregnancy Stress Exposures and Postpartum Serum Metabolomic Profiles in Mothers.
Svensson K, India-Aldana S, Saddiki H … +7 more , Petrick LM, Guan H, Hernández-Chávez C, Téllez-Rojo MM, Wright RO, Wright RJ, Colicino E
Metabolites · 2026 May · PMID 42188021 · Full text
BACKGROUND/OBJECTIVES: Women exposed to high psychosocial stress in pregnancy have higher risk of postpartum health conditions, but it still is unknown whether high pregnancy stress exposure alters the maternal metabolom...
BACKGROUND/OBJECTIVES: Women exposed to high psychosocial stress in pregnancy have higher risk of postpartum health conditions, but it still is unknown whether high pregnancy stress exposure alters the maternal metabolome at one-month postpartum. METHODS: We analyzed data from 625 women participating in the PROGRESS study, a longitudinal pregnancy cohort. Women answered validated psychometric tests (i.e., EPDS, PSS and NLE) during the second or third trimester of pregnancy and provided serum samples at one-month postpartum for metabolomic assessment. Untargeted metabolomics were analyzed using chromatography high-resolution mass spectrometry (LC-HRMS). We used a metabolome-wide association study, using both traditional robust regressions and variance tests, to evaluate associations between pregnancy psychosocial stress and one-month postpartum serum metabolomics. RESULTS: We found a few nominally significant associations between prenatal psychosocial stress scores and the maternal metabolome. However, these findings did not remain after adjusting for multiple testing, with the only exception of epiandrosterone glucuronide, a steroid hormone metabolite, and lithocholyltaurine, a lipid-like molecule. CONCLUSIONS: We did not find significant associations between prenatal psychosocial stress and postpartum serum metabolomic profiles, except for two metabolites showing suggestive associations warranting further investigation.
HR-LCMS/MS-Based Dereplication of Plant-Derived Autophagy Inducers Revealed as a New Glabrol Producer.
Bolikhova AK, Alferova VA, Izzi AR … +8 more , Nikandrova AA, Kudryakova GK, Zhitlov MY, Guseva EA, Karpov DS, Lukianov DA, Dontsova OA, Sergiev PV
Metabolites · 2026 May · PMID 42188020 · Full text
BACKGROUND/OBJECTIVES: Autophagy is an important cellular self-cleansing process whose normal functioning is essential for preventing many age-related diseases. The search for and study of new autophagy activators allows...
BACKGROUND/OBJECTIVES: Autophagy is an important cellular self-cleansing process whose normal functioning is essential for preventing many age-related diseases. The search for and study of new autophagy activators allows the proposal of novel therapeutic approaches for the treatment of age-related diseases. Medical plants are a rich source of bioactive compounds with variable functions. In this study, we propose an HR-LCMS/MS-based technique for identifying the principal autophagy activators in plant extracts. METHODS: We performed a Western blot analysis of the autophagy-inducing activity of plant extract HPLC fractions on a model of SH-SY5Y cells. The composition of the fractions showing autophagy-activating potential was determined via HR-LCMS/MS. RESULTS: We analyzed five plants known to produce autophagy activators and proved the ability of the method to detect the main bioactive compounds. Additional screening demonstrated for the first time that is a producer of the autophagy-inducer glabrol. CONCLUSIONS: The described HR-LCMS/MS-based method for identifying autophagy activators in multicomponent plant extracts is effective and could be used for further high-throughput screening.
Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review.
Gong H, Miao J, Yuan J … +6 more , Zhu Y, Xiang H, Yu Y, Zhou S, Zhang Q, Han Y
Metabolites · 2026 Apr · PMID 42188019 · Full text
: Research indicates that hepatic gluconeogenesis mediates metabolic coupling between the liver and muscles via the Cori cycle and participates in liver-brain axis communication through its metabolic products and regulat...
: Research indicates that hepatic gluconeogenesis mediates metabolic coupling between the liver and muscles via the Cori cycle and participates in liver-brain axis communication through its metabolic products and regulatory networks, thereby linking it to the pathogenesis of depression. Together, these mechanisms form the molecular basis for the antidepressant effects of exercise-regulated hepatic gluconeogenesis. Regular exercise promotes skeletal muscle contraction, causing the muscles to release more lactate into the circulatory system. Lactate acts as a substrate for gluconeogenesis and activates downstream signaling pathways, thereby enhancing the gluconeogenic response. During exercise, glycogenolysis directly provides energy, while lactate produced by glycolysis enters the liver via the Cori cycle to serve as a substrate for gluconeogenesis. By maintaining blood glucose homeostasis, this process ensures a stable energy supply to the brain, thereby improving cognitive and emotional functions. This study aims to elucidate how key substrates, regulatory factors, and rate-limiting enzymes involved in hepatic gluconeogenesis and exercise influence brain energy supply, cognitive function, and emotional regulation during depression. It seeks to identify the potential targets and mechanisms through which exercise exerts its antidepressant effects via hepatic gluconeogenesis, with the goal of providing a theoretical foundation for research into the mechanisms of depression and for clinical exercise interventions. : This review conducted a comprehensive search of the recent literature on exercise, hepatic gluconeogenesis, and depression in major domestic and international databases. Adopting an interdisciplinary approach that integrates hepatic gluconeogenesis and exercise, it synthesizes existing evidence to explore the metabolic mechanisms by which exercise improves depression through the regulation of hepatic gluconeogenesis pathways. : Research has found that exercise may modulate hepatic gluconeogenic substrates and regulate the expression of cAMP-responsive element-binding protein in states of depression, regulatory factors such as liver kinase B1, forkhead box protein 01, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator activated receptor gamma co activator factor 1 alpha are used to affect key rate limiting enzymes of hepatic gluconeogenesis, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, enhance hepatic gluconeogenesis processes, maintain blood glucose homeostasis, ensure brain energy supply, and improve depression. : Exercise intervention targeting hepatic gluconeogenesis may be a potential therapeutic strategy for depression.
Influence of Co Irradiation on the Volatile Organic Compounds of Cnidii Fructus.
Huang J, Liu Y, Liu Y … +3 more , Yan J, Li S, Huang D
Metabolites · 2026 Apr · PMID 42188018 · Full text
BACKGROUND/OBJECTIVES: As a traditional Chinese medicinal herb, Cnidii Fructus is widely used in clinical practice. Its volatile organic compounds (VOCs) are closely related to its antipruritic effect and insecticidal pr...
BACKGROUND/OBJECTIVES: As a traditional Chinese medicinal herb, Cnidii Fructus is widely used in clinical practice. Its volatile organic compounds (VOCs) are closely related to its antipruritic effect and insecticidal properties. Due to the susceptibility of this medicinal herb to mold contamination, adopting appropriate sterilization measures is of great significance for its storage. Co irradiation is widely used for this purpose due to its various advantages. METHODS: This study employed Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) combined with multivariate statistical analysis to systematically investigate the influence of different Co irradiation doses (0, 3, 6, 9 kGy) on the VOCs of Cnidii Fructus and associated metabolic regulatory mechanisms. RESULTS: A total of 115 VOCs were tentatively identified. Statistical analysis revealed dose-dependent effects: 3 kGy irradiation caused the least compositional perturbation, best preserving original chemical characteristics; 6 kGy induced more pronounced compositional changes; and 9 kGy triggered substantial chemical composition reconstruction. Differential metabolite enrichment analysis indicated that medium and high doses of irradiation primarily perturbed central carbon metabolic pathways, including pyruvate metabolism, glycolysis/gluconeogenesis, and glyoxylate and dicarboxylate metabolism. Key differential components were tentatively identified (e.g., α-Thujone, α-Pinene, β-Pinene) that possess pharmacological activities closely associated with the traditional efficacy of Cnidii Fructus. CONCLUSIONS: When the irradiation dose is 3 kGy, the VOCs profile of Cnidii Fructus is most similar to that of the non-irradiated control group, suggesting that its compositional profile may be closer to that of traditional high-quality medicinal materials. Meanwhile, the differential metabolites and core metabolic pathways identified in this study can provide a chemical reference for the quality control of irradiated Cnidii Fructus. The findings provide a theoretical basis and technical support for the rational application of Co irradiation sterilization in the processing of Chinese medicinal materials and their powders.
Circulating Wnt Signaling Inhibitors and Osteoprotegerin in Women with Newly Diagnosed Overt Thyroid Dysfunction.
Miteva MZ, Orbetzova MM, Nonchev BI … +2 more , Davcheva DM, Gigov K
Metabolites · 2026 Apr · PMID 42188017 · Full text
: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotege...
: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. : This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. : Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls ( < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, = 0.001) and FT4 (r = 0.43, = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, = 0.007). A strong positive correlation was found between DKK-1 and SOST ( < 0.001), while DKK-1 was negatively associated with age ( < 0.05). : Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune-bone interactions in thyroid-related changes in bone metabolism.
Association Between Sperm Metabolites and Field Fertility in Angus Bulls.
Roberts SR, Moorey SE, Lonas AB … +5 more , Hessock EA, Abiodun BA, Campagna SR, Schrick FN, Menegatti Zoca S
Metabolites · 2026 Apr · PMID 42188016 · Full text
BACKGROUND/OBJECTIVES: Understanding the causes of bull subfertility and developing reliable diagnostic tools are critical to reducing economic losses caused by reproductive failure in beef cattle. Metabolomic analysis o...
BACKGROUND/OBJECTIVES: Understanding the causes of bull subfertility and developing reliable diagnostic tools are critical to reducing economic losses caused by reproductive failure in beef cattle. Metabolomic analysis of sperm from bulls with diverging field fertility may provide insights on sperm metabolism that are associated with fertility. The objective was to determine metabolomic differences in sperm from bulls with differing field fertility. METHODS: Angus bulls ( = 15) were classified based on a composite field fertility index (CFI). Frozen-thawed semen straws ( = 10 per bull) underwent a Percoll gradient sperm purification process. Metabolomic analysis was performed through ultra-high performance liquid chromatography coupled high resolution mass spectrometry at the University of Tennessee Biological and Small Molecule Mass Spectrometry Core. The general linear model (GLM) procedure of Statistical Analysis System (SAS) was used to evaluate linear and quadratic relationships between metabolites and CFI. Furthermore, the MIXED procedure was used to determine differences in metabolite abundance between the four highest and lowest fertility bulls. Significance was determined when ≤ 0.05 and tendency was declared when ≤ 0.10. RESULTS: A total of 75 metabolites were detected. Quadratic relationships with fertility were observed for kynurenine, xanthine, and ophthalmate. Tricarballylic acid and creatinine showed a negative linear relationship with fertility. When differences in metabolite abundance were assessed between the four highest and lowest fertility bulls, -acetylglutamate and -acetylglutamine had greater abundance in low fertility bulls. CONCLUSIONS: Metabolites kynurenine, xanthine, ophthalmate, tricarballylic acid, and creatinine are potential fertility markers to identify subfertile bulls from a breeding population. These metabolites have promising future implications in the diagnosis and treatment of beef bull subfertility.
Nutrition, Metabolism, and Physiology in Aquatic Animals: Current Advances and Future Directions.
Li X, Ji RL
Metabolites · 2026 Apr · PMID 42188015 · Full text
Aquaculture nutrition research is undergoing a substantive conceptual transition [...].
Aquaculture nutrition research is undergoing a substantive conceptual transition [...].
Prolonged Deltamethrin Exposure Induces Dose-Dependent Glycerol Overproduction and Efficient Deltamethrin Removal by .
Yavuz M, Yavuz HG, Kaya RA … +3 more , Eren O, Bereketoglu C, Turanli B
Metabolites · 2026 Apr · PMID 42188014 · Full text
: Pest management strategies rely on insecticides such as deltamethrin (DM), a commonly applied type II pyrethroid. As a natural component of food-associated microflora, inevitably encounters DM residues in crops used f...
: Pest management strategies rely on insecticides such as deltamethrin (DM), a commonly applied type II pyrethroid. As a natural component of food-associated microflora, inevitably encounters DM residues in crops used for fermentation processes, including dough leavening and winemaking. However, the prolonged effect of DM exposure on yeast fermentation performance and its capacity to remove DM remained unclear. : In this study, was continuously exposed to a non-lethal concentration (10 mg/L) and a low-inhibition toxic concentration (30 mg/L) of DM for 30 days. : Yeast exhibited high removal capacity, removing 98.05 ± 1.2% and 98.28 ± 0.4% of DM at 10 mg/L and 30 mg/L, respectively. Prolonged exposure to DM at both concentrations did not significantly affect biomass formation, glucose consumption, ethanol production, or acetic acid levels. In contrast, glycerol production increased markedly, reaching 1.1 g/L and 1.5 g/L in cultures exposed to 10 mg/L and 30 mg/L DM, respectively. Consistent with these changes, the expression levels of GPD1 and GPD2, which encode rate-limiting enzymes in glycerol biosynthesis, were upregulated in a dose-dependent manner. : Given the fact that is a workhorse for the biotechnological industry and has a wide range of applications, including in the food industry, elevated glycerol production in yeast under DM exposure is noteworthy in terms of yeast-based applications.
A Receptor Activation Restores Lipid and Mitochondrial Homeostasis, Limiting Persistence in Human Monocytes.
Pereira AMR, Santos PMFD, Rosa TLSA … +13 more , Díaz Acosta C, Vasconcelos KGC, Gutierres LD, Costa FMR, Lery LMS, Garrett R, Alves MA, Dias AA, Lara FA, Rodrigues LS, Pinheiro RO, Pessolani MCV, Berrêdo-Pinho M
Metabolites · 2026 Apr · PMID 42188013 · Full text
Leprosy is a chronic infection caused by that, in addition to Schwann cells, macrophages, and adipocytes, also infects human peripheral blood monocytes and subverts their metabolism in its favor. Infection is marked by...
Leprosy is a chronic infection caused by that, in addition to Schwann cells, macrophages, and adipocytes, also infects human peripheral blood monocytes and subverts their metabolism in its favor. Infection is marked by cholesterol and fatty acid accumulation in lipid droplets (LDs), and a reduction in mitochondrial membrane potential (Δψm). Previous studies showed that downregulates adenosine receptor A (AR) expression in Schwann cells, while activation reduces LD accumulation and bacterial viability. Since AR controls immunometabolic response, we investigated whether AR signaling restrains -driven reprogramming in monocytes. Peripheral blood mononuclear cells from healthy donors were enriched for monocytes and infected with in the presence or absence of adenosinergic modulators (5'AMP, adenosine (ADO), AR agonist CGS21680, the antagonist ZM241385, or AR antagonist, MRS1754). We used flow cytometry, fluorescence microscopy, and RT-qPCR to evaluate purinergic components expression and bacillary viability. LDs and Δψm were measured by fluorescence microscopy, and extracellular levels of inosine (INO) and hypoxanthine (HPX) by LC-MS/MS. The results show that infection increased CD39, ADA, AR and AR expression, decreased ENT1, AR and AR, and raised extracellular INO and HPX. In addition, 5'AMP, ADO and CGS21680 reversed infection-induced LD accumulation. CGS21680 also restored Δψm and decreased intracellular viability. Our data suggest that suppresses AR signaling to favor its survival in monocytes, indicating that the extracellular ADO-AR pathway may be a potential target to limit early infection.
Nutraceutical Profiles and FTIR Fingerprints of Comorian and var. .
Irchad A, Kassimi CE, Salmata I … +8 more , Mansouri H, Thabiti Y, Hadday S, Mohamed FA, Aboutayeb R, Abdou Azali H, Delsart C, Hssaini L
Metabolites · 2026 Apr · PMID 42188012 · Full text
BACKGROUND/OBJECTIVES: (robusta) and var. (excelsa) cultivated in the Comoros islands represent understudied coffee varieties grown in a unique volcanic terroir. Despite their agricultural significance and potential b...
BACKGROUND/OBJECTIVES: (robusta) and var. (excelsa) cultivated in the Comoros islands represent understudied coffee varieties grown in a unique volcanic terroir. Despite their agricultural significance and potential bioactive value, no comprehensive biochemical or nutritional characterization of these Comorian coffees had previously been conducted. This study therefore aimed to provide the first integrated biochemical and nutritional characterization of both varieties and to evaluate the influence of the islands' specific edaphoclimatic conditions on their chemical composition. METHODS: An integrated analytical approach was employed, combining UV-Vis spectrophotometry, HPLC, ionomics, and FTIR-ATR spectroscopy to quantify polyphenols, flavonoids, caffeine, soluble sugars, antioxidant activity, mineral profiles, and macromolecular composition of green coffee beans from both species. RESULTS: Robusta exhibited significantly higher levels of total polyphenols (121.79 ± 2.73 mg GAE/g), total flavonoids (29.43 ± 2.20 mg QE/g), caffeine (1.52% /), total soluble sugars (60.47 ± 3.37 mg GE/g), and antioxidant activity (64.97 ± 6.25 mM Trolox eq/g). Conversely, excelsa demonstrated a distinct mineral profile, with significantly higher concentrations of magnesium, calcium, sodium, zinc, and copper. FTIR spectroscopy confirmed distinct vibrational fingerprints between the two species, particularly in lipid and carbohydrate signatures. CONCLUSIONS: These findings position Comorian robusta as a potent source of antioxidants and stimulants, while excelsa offers a nutritionally balanced profile with nutraceutical potential, providing a scientific basis for valorizing both varieties as high-value niche products and contributing to the preservation of coffee agro-biodiversity.
Revealing the Formation Mechanism of Key Metabolites During Japonica Rice Storage Driven by Microbial Functional Genes.
Li X, Deng W, Zhang Z … +2 more , Tong H, Cao Y
Metabolites · 2026 Apr · PMID 42188011 · Full text
BACKGROUND: To elucidate the evolution of metabolites and fungal communities during storage of fragrant japonica rice (Liaoxiangjing 1396), and to investigate the biosynthetic mechanisms of key compounds and their associ...
BACKGROUND: To elucidate the evolution of metabolites and fungal communities during storage of fragrant japonica rice (Liaoxiangjing 1396), and to investigate the biosynthetic mechanisms of key compounds and their association with quality deterioration, this study examined rice samples stored under simulated conditions for 16 months. METHOD: Samples were collected at 4-month intervals (designated R20, R14, R13, R12, and R11). Metabolites were identified using GC-MS non-targeted metabolomics, while fungal community structure was analyzed through metagenomics. Core mechanisms were further elucidated via PLS-DA, KEGG pathway enrichment, and multiomics association analysis. RESULT: Results demonstrated that the fatty acid content of rice increased initially and then stabilized (from 12.24 mg/g in R20 to 17.63 mg/g in R12). A total of 263 metabolites were identified, with oxygenated organic compounds (38 species) and lipids/lepidid molecules (24 species) as the predominant categories. Twelve key differential metabolites were screened from the R20 and R12 groups, involving five major metabolic pathways, including amino acid metabolism and lipid metabolism. In the fungal community, (60.2%) and (38.19%) were dominant taxa, with a specific species ( sp.) identified as a core potential biomarker. Multiomics association analysis revealed that dominated the ndhB energy metabolism pathway, while multiple bacteria cooperatively regulated the mcp chemotaxis pathway, interacting with monosaccharide and amino acid accumulation. CONCLUSIONS: This study reveals that the storage quality deterioration of fragrant japonica rice is driven by the "metabolite-microbe-pathway" chain regulation, and the dynamic changes in key metabolites and fungal communities can serve as quality early warning targets.
Network Pharmacology Analysis of Glycyrrhetinic Acid in Metabolic Dysfunction-Associated Steatotic Liver Disease.
Jaramillo-Morales OA, Cruz-Trujillo R, De la Torre-Sosa CN … +5 more , Corzo-Gómez JC, Domínguez-Cruz DC, Cruz-Cadena RE, Vega-Cabrera NV, Espinosa-Juárez JV
Metabolites · 2026 Apr · PMID 42188010 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder driven by tightly interconnected metabolic, inflammatory, and lipid dysregulation pathways. Glycyrrhetinic acid, a pentacyclic...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder driven by tightly interconnected metabolic, inflammatory, and lipid dysregulation pathways. Glycyrrhetinic acid, a pentacyclic triterpenoid derived from species, has demonstrated anti-inflammatory and hepatoprotective activities in previous experimental studies. : This study aimed to systematically investigate the potential molecular targets and signaling pathways of glycyrrhetinic acid in MASLD using an integrated network pharmacology and molecular docking strategy. : Predicted protein targets of glycyrrhetinic acid and MASLD-associated genes were collected from public databases. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the maximal clique centrality algorithm in Cytoscape. Functional annotation was performed through Gene Ontology and KEGG pathway enrichment analyses. Molecular docking simulations were subsequently conducted to assess the binding affinity of glycyrrhetinic acid with biologically prioritized targets derived from the network analysis. : Intersection analysis identified 26 shared targets between glycyrrhetinic acid and MASLD. PPI network analysis highlighted IL6, TNFα, AKT1, and PPARγ as central hub genes. Functional enrichment indicated that these targets were mainly involved in NF-κB, TNFα, and PI3K-Akt signaling pathways. Molecular docking results revealed favorable predicted binding affinities, with glycyrrhetinic acid exhibiting the strongest binding toward PPARγ among the evaluated targets. : This integrative in silico analysis suggests that glycyrrhetinic acid may interact with multiple MASLD-related targets involved in inflammatory and metabolic regulation. These findings provide a computational framework for target prioritization and support further experimental investigations to elucidate the pharmacological relevance of glycyrrhetinic acid in MASLD.
Age- and Sex-Specific Patterns of Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Apparently Healthy Chinese Adults: A Cross-Sectional Study.
Hu KW, Cheng BL, Ni PS … +2 more , Wang ZZ, Li FH
Metabolites · 2026 Apr · PMID 42188009 · Full text
This study examined age- and sex-specific correlates of arterial stiffness, assessed by the cardio-ankle vascular index (CAVI), in apparently healthy Chinese adults using an anthropometric-metabolic-inflammatory framewor...
This study examined age- and sex-specific correlates of arterial stiffness, assessed by the cardio-ankle vascular index (CAVI), in apparently healthy Chinese adults using an anthropometric-metabolic-inflammatory framework, and descriptively compared subgroup association patterns across these domains. In this cross-sectional study, 525 apparently healthy Chinese adults aged 20-78 years were included. Regression models with age-by-indicator interaction terms were used to test whether the age-CAVI association varied across anthropometric, metabolic, and inflammatory indicators. Sex-adjusted analyses were applied to the overall sample, sex-stratified analyses were used to characterize sex-specific patterns, and the Benjamini-Hochberg false discovery rate correction was applied for multiple interaction tests. CAVI increased progressively with age, with a steeper age-CAVI association after 50 years ( < 0.05). Notably, females showed a transient midlife elevation. Association patterns appeared to differ by sex. In the sex-stratified interaction analyses, anthropometric signals were more prominent in men, particularly for height ( < 0.01), whereas metabolic-related interaction signals were more evident in women, with triglycerides providing the clearest corresponding signal and low-density lipoprotein cholesterol (LDL-C) showing a weaker accompanying pattern; the C-reactive protein (CRP)-related contrast was not retained after additional adjustment for blood pressure and smoking. CAVI increased with age, with a steeper rise after midlife and a transient midlife elevation in women. The association patterns across anthropometric, metabolic, and inflammatory indicators appeared to differ by sex, with signals from the anthropometric domain appearing more evident in men and metabolic-related signals appearing more evident in women. These findings suggest that age- and sex-specific interpretation of CAVI may be informative in preventive health check-up settings.
Cross-Sectional Associations of Metabolically Healthy Obesity, Lifestyle Factors, and Steatotic Liver Disease in Adults from the Fels Longitudinal Study.
Garza AL, Choh AC, Blangero J … +3 more , Bauer CX, Czerwinski SA, Lee M
Metabolites · 2026 Apr · PMID 42188008 · Full text
OBJECTIVE: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults. METHODS: We analyzed 676 non-Hispanic white adults (18-95 years; 55.8% female...
OBJECTIVE: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults. METHODS: We analyzed 676 non-Hispanic white adults (18-95 years; 55.8% female) from the Fels Longitudinal Study using a cross-sectional design. Participants were classified into metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO) phenotypes. Metabolically unhealthy status was defined as the presence of ≥1 metabolic dysfunction, consistent with prior epidemiological definitions; secondary analyses using ≥2 were also performed. Obesity was defined using DXA-derived body fat percentage. Liver fat (%) was quantified using magnetic resonance imaging, and hepatic steatosis was defined as liver fat > 5.56%. Multivariable linear and probit regression models were used to evaluate associations, adjusting for demographic and lifestyle covariates; secondary models additionally examined dietary intake. RESULTS: Mean liver fat was 5.95% (SE = 0.23), and steatosis was present in 29.8% of participants. Compared to MHNW individuals, liver fat was significantly higher in MHO (mean 3.77% vs. 2.67%), MUNW (4.63%), and MUO (8.47%) phenotypes. After covariate adjustment, liver fat was 33.8% (95% CI: 13.7-57.5%) higher in MHO, 28.1% (10.1-49.0%) higher in MUNW, and 113.0% (85.3-144.7%) higher in MUO relative to MHNW. Corresponding increases in steatosis probabilities were observed across phenotypes. No individual dietary component or dietary pattern was significantly associated with liver fat after adjustment. CONCLUSIONS: Metabolically healthy obesity was associated with higher liver fat and steatosis probability compared with metabolically healthy normal weight, with levels comparable to metabolically unhealthy normal weight individuals. These findings suggest that the absence of overt metabolic abnormalities does not necessarily indicate a metabolically benign state with respect to liver fat accumulation. Given the cross-sectional design, these results should be interpreted as associations rather than causal relationships.
The Effect of Heat Stress on Broiler Meat Quality and the Mechanisms Underlying Muscle Acidification: An In Vivo and In Vitro Study.
Xu Y, Weng Z, Huang X … +4 more , Chao X, Zhang X, Zhang X, Luo Q
Metabolites · 2026 Apr · PMID 42188007 · Full text
This study investigated how chronic heat stress affects meat quality and post-slaughter muscle acidification in slow-growing yellow-feathered broilers, focusing on the roles of ALDOB and HSP90B1 in glycometabolism. From...
This study investigated how chronic heat stress affects meat quality and post-slaughter muscle acidification in slow-growing yellow-feathered broilers, focusing on the roles of ALDOB and HSP90B1 in glycometabolism. From 100 to 120 days of age, broilers were kept either under thermoneutral conditions (25 ± 1 °C, N group) or cyclic heat stress (32 ± 1 °C for 9 h/day, H group). Meat quality traits (pH, shear force, drip loss, color) were measured at 0, 24, and 48 h of refrigeration (4 °C). Free amino acid and fatty acid profiles were analyzed. DF-1 cells were exposed to 43 °C for functional assays of and . Chronic heat stress reduced body weight, altered flavor precursors, and induced PSE-like characteristics (lower pH, higher shear force, increased drip loss, paler color), especially in leg muscles. and were upregulated in both tissues and cells. overexpression promoted glucose consumption, while suppressed lactic acid production. Chronic heat stress impairs growth and flavor precursors and exacerbates post-slaughter muscle acidification (primarily driven by ATP hydrolysis, with lactic acid as a secondary contributor). and may dually regulate glycometabolism under heat stress.
Lysolecithin Improves Lipid Metabolism and Gut Microbiota: An Integrated Transcriptome and Microbiome Analysis in Largemouth Bass () Fed Stearin-Based High-Lipid Diets.
Zhang Y, Feng T, Dong Z … +5 more , Ke T, Storebakken T, Cai W, Shi B, Huang L
Metabolites · 2026 Apr · PMID 42188006 · Full text
Supplementing aquafeeds with emulsifiers can enhance lipid utilization, yet the physiological effects of lysolecithin, derived from enzymatic lecithin conversion, remain under-explored. This study examined the effects o...
Supplementing aquafeeds with emulsifiers can enhance lipid utilization, yet the physiological effects of lysolecithin, derived from enzymatic lecithin conversion, remain under-explored. This study examined the effects of lysolecithin supplementation on hepatopancreatic transcriptome and gut microbiota in largemouth bass () fed stearin-based high-lipid diets. Two diets were formulated: a control containing 130 g kg stearin fish oil (SO), and in the experimental diet (SL), 3.1 g kg rapeseed oil was replaced with 3.1 g kg lysolecithin oil. Each diet was fed to three replicate groups for 56 days. Hepatopancreas and distal intestine were sampled for transcriptome profiling, and gut microbiota were characterized at 28 and 56 days. Lysolecithin supplementation resulted in 424 differentially expressed genes compared with the control (322 up- and 102 downregulated). KEGG enrichment indicated major effects on lipid metabolic processes, notably activation of the PI3K-AKT signaling pathway, enhanced adipocyte lipolysis, and modulation of adipocytokine signaling, suggesting improved insulin sensitivity and lipid mobilization. Histological analysis showed mild distal intestinal inflammation in the SO group. Gut microbiota composition shifted over time; lysolecithin increased the relative abundance of and reduced potential opportunistic taxa compared with the control. Overall, dietary inclusion of lysolecithin improved lipid utilization in largemouth bass, likely by enhancing lipid metabolism and promoting beneficial gut microbial profiles. These findings support lysolecithin as a promising feed additive for optimizing high-lipid aquafeeds.
The Hormonal-Metabolic Puzzle of PCOS: Linking AMH Levels, Body Fat Distribution, and Insulin Resistance in Overweight and Obese Women.
Gorzko A, Nawrocka-Rutkowska J, Brodowska A … +3 more , Śliwak E, Starczewski A, Szydłowska I
Metabolites · 2026 Apr · PMID 42188005 · Full text
: The relationship between AMH (anti-Müllerian hormone) levels, fat distribution, and insulin resistance in women with PCOS has been widely studied, yet findings remain inconsistent. Recent guidelines emphasize the growi...
: The relationship between AMH (anti-Müllerian hormone) levels, fat distribution, and insulin resistance in women with PCOS has been widely studied, yet findings remain inconsistent. Recent guidelines emphasize the growing role of AMH in PCOS diagnosis and suggest its potential inclusion among diagnostic criteria, highlighting its relevance for guiding therapeutic management. : This retrospective study aimed to evaluate the association between AMH levels and metabolic parameters in overweight and obese reproductive-age women with PCOS. Ethical approval was obtained from the bioethics committee. : Two groups of 52 women each were selected from PCOS patients treated at our clinic between 2024 and 2025: one with a waist-to-hip ratio (WHR) ≤ 0.85 and the other with a WHR > 0.85. Venous blood samples were collected to measure AMH, fasting glucose, and fasting insulin. Body height and weight were recorded to calculate body mass index (BMI), and insulin resistance was assessed using HOMA-IR. Waist and hip circumferences were measured to determine WHR. : The association between central adiposity and AMH in overweight and obese women with PCOS depended on insulin resistance. In insulin-resistant women, higher WHR was linked to lower AMH, whereas in women without insulin resistance, higher WHR corresponded to higher AMH levels. : Insulin resistance appears to influence AMH in opposite directions depending on a woman's WHR, suggesting its potential role in tailoring individualized treatment strategies.
High-Resolution Magic Angle Spinning Metabolomic Profiling of IDH-Wild-Type Glioblastoma Reveals a Composite Surgical Sampling Signature Shaped by Clinical and Anatomical Tumor Features.
Todeschi J, Bund C, Outilaft H … +2 more , Cebula H, Namer IJ
Metabolites · 2026 Apr · PMID 42188004 · Full text
BACKGROUND/OBJECTIVES: Tissue-based metabolomic readouts in IDH-wild-type glioblastoma may be strongly shaped by how tumor tissue is surgically accessed and sampled. We aimed to determine whether, and to what extent, sur...
BACKGROUND/OBJECTIVES: Tissue-based metabolomic readouts in IDH-wild-type glioblastoma may be strongly shaped by how tumor tissue is surgically accessed and sampled. We aimed to determine whether, and to what extent, surgical sampling context structures the HRMAS metabolic landscape, and to disentangle sampling-related contributions from clinico-anatomical confounders. METHODS: We retrospectively analyzed 99 patients with de novo IDH-wild-type glioblastoma (35 biopsy-only, 64 resection: 40 gross-total, 21 near-total, 3 subtotal), yielding 166 HRMAS spectra and 47 quantified metabolites (nmol/mg). Patient-level profiles were compared using PCA, metabolite-wise testing, pathway-level aggregation (10 pathways), and variance partitioning by PERMANOVA, both unadjusted and adjusted for age, WHO PS, deep-seated location, midline involvement, multifocality, MGMT methylation, and eloquent area. Sensitivity analyses included clinico-anatomically restricted subgroups, 15 canonical metabolite ratios, and Probabilistic Quotient Normalization. Intratumoral heterogeneity was assessed in 44 multi-sampled patients. RESULTS: Biopsy-only and resection-derived cases separated along PC1 in unsupervised PCA (62.6% variance; < 0.001), with 42/47 metabolites differing after FDR correction. However, the surgical group explained only 2.6% of the total variance (PERMANOVA = 0.026), and this share was no longer significant after confounder adjustment ( = 0.39). Clinico-anatomical restriction progressively attenuated the effect (42/47 → 1/47 significant metabolites). Ratio-based and PQN analyses showed a residual compositional difference beyond scaling (13/15 ratios; 16/47 metabolites). Intratumoral heterogeneity was greater in resections and preserved in an n-matched analysis ( = 0.020). CONCLUSIONS: The apparent biopsy-versus-resection metabolic difference is largely a composite signal reflecting clinico-anatomical patient selection with a smaller tissue-composition contribution. Biopsy-only and resection-derived specimens should not be pooled uncritically in tissue-based metabolomic studies of glioblastoma.
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