Metabolites[JOURNAL]
Sun
200 papers
Metabolite Profiling and Pathway Elucidation of 2-Fluorodeschloroketamine and 2-Fluoro-N-ethylketamine in Rats Using HPLC-QTOF Mass Spectrometry.
Zhang Y, Wang Q, Wang Y … +4 more , Wu Y, Tian X, Dai Y, Cai Y
Metabolites · 2026 Jun · PMID 42346374 · Full text
: This study aimed to employ a High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry(HPLC-QTOF/MS) system to detect potential metabolites of 2-Fluorodeschloroketamine (2-FDCK) an...
: This study aimed to employ a High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry(HPLC-QTOF/MS) system to detect potential metabolites of 2-Fluorodeschloroketamine (2-FDCK) and 2-fluoro-N-ethylketamine (2-FXE) in rats, elucidate their metabolic pathways, and analyze the metabolic differences between the two compounds. Such exploration is vital for understanding their distinct drug effects and providing a reference for forensic toxicological assessment of new phencyclidine-class psychoactive substances. : Twelve SD rats were randomly split into two groups. After a 12 h fast, each group was administered a single intraperitoneal injection of one drug at 0.045 mg/kg. At 1 h and 2 h post-dosing, the rats were euthanized, and blood, liver tissue, and urine samples were promptly collected. These samples underwent rapid solvent extraction for pretreatment and were then analyzed using HPLC-QTOF. Metabolites were identified through database searches and secondary mass spectrometry fragment ion analysis. : Comparative analysis of metabolite types, formation times, and chromatographic peak response intensities between the two groups showed that metabolic pathways were mostly consistent. However, significant differences were observed in metabolic reaction types, metabolite formation times, and response intensities, likely stemming from chemical structural disparities. : The findings offer crucial insights into the drug effect differences between the two compounds and establish a valuable reference for forensic toxicological evaluation of new phencyclidine-class psychoactive substances.
Relationship Between Adipose Tissue and Liver Dysfunction in Women with Polycystic Ovary Syndrome and Metabolic Syndrome.
de Medeiros SF, Maciel GAR
Metabolites · 2026 Jun · PMID 42346373 · Full text
Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adip...
Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue-liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies.
Integrated Chemical Profiling, Serum Pharmacochemistry, and Network Pharmacology to Elucidate the Anti-Hyperlipidemic Effects of Retz. Fruits from Different Geographical Origins.
He Y, Feng Q, Zhao W … +1 more , Tian L
Metabolites · 2026 Jun · PMID 42346372 · Full text
BACKGROUND: The fruits of Retz. (FRL) is a traditional medicinal and edible fruit widely used in Xinjiang for its potential health benefits. Its chemical variations across geographical origins remain poorly understood,...
BACKGROUND: The fruits of Retz. (FRL) is a traditional medicinal and edible fruit widely used in Xinjiang for its potential health benefits. Its chemical variations across geographical origins remain poorly understood, as do the molecular mechanisms underlying its anti-hyperlipidemic effects. This study aimed to characterize the chemical profile of FRL extract (FRLE) from different origins, identify its bioactive constituents and metabolites in vivo, and evaluate its efficacy and potential mechanisms against HLP. METHODS: UPLC-QTOF-MS was employed for qualitative and quantitative profiling, combined with PCA to differentiate samples from five origins. An HLP mouse model was established to evaluate the pharmacodynamic effects, while acute and sub-chronic toxicity tests assessed safety. Serum pharmacochemistry was used to track absorbed constituents and metabolites. Finally, network pharmacology, molecular docking, and Western blot were integrated to elucidate the underlying mechanisms. RESULTS: A total of 60 compounds were identified in FRLE, with 20 key components quantified via the TOF-MRM mode. PCA indicated that the Yamalike Mountain samples possessed the most diverse chemical profile and the highest response of active markers. Pharmacodynamic results showed that FRLE (extraction yield 24.19%) significantly improved TC, LDL-C, and corrected abnormal HDL-C levels in HLP mice, while H&E staining confirmed the alleviation of hepatic steatosis. Safety evaluations revealed no significant acute or cumulative toxicity at the maximum feasible dose of 16.6 g/kg. In rat plasma, 15 prototypes and 14 metabolites were identified. FRLE acted on the "Lipid and Atherosclerosis" pathway by modulating key targets, including NFE2L2, CYP1A1, NOS3, and MAPK1. CONCLUSIONS: Our findings demonstrate that FRLE is a safe and effective candidate for the management of hyperlipidemia. This study establishes a link between the material basis and biological mechanisms of FRL, thereby providing a scientific foundation for its further resource development and clinical application.
Effects of Dietary Protein Levels on Growth, Serum Physiology, Protein and Lipid Metabolism, and Antioxidant Responses in Black Carp ().
Zhang J, Yang S, Zhu Y … +5 more , Yu J, Zhang Y, Li J, Lin C, Wu C
Metabolites · 2026 Jun · PMID 42346371 · Full text
: Dietary protein optimization is an important nutritional strategy for improving growth and physiological responses, and antioxidant homeostasis in fish. : In this study, 540 black carp (initial body weight: 10.50 ± 1.0...
: Dietary protein optimization is an important nutritional strategy for improving growth and physiological responses, and antioxidant homeostasis in fish. : In this study, 540 black carp (initial body weight: 10.50 ± 1.00 g) were randomly assigned into recirculating tanks (500 L) fed with six dietary protein levels (30-44% crude protein) for an 8-week feeding trial with triplicates per treatment and 30 fish per replicate. After the trial, fish body, blood, hepatopancreas, and intestinal samples were collected for body composition, serum biochemical parameters, metabolism, and antioxidant indices' analyses. : Results showed fish fed 38% protein (PT38) exhibited the highest weight gain ( < 0.05), with no further improvement at higher protein levels. Compared with PT30 group, PT38 group significantly promoted protein deposition by upregulating transcript levels of insulin-like growth factors () via activating mechanistic target of rapamycin () signaling pathway. PT38 could improve fatty acid oxidation by heightening levels of carnitine palmitoyl transferase 1α (), peroxisome proliferator-activated receptor α () and . Meanwhile, PT38-PT41 significantly inhibit expression of fatty acid synthesis and lipid droplet deposition-related genes, including acetyl-CoA carboxylase (), fatty acid synthase (), and perilipin 2 ( < 0.05). PT38 significantly enhanced antioxidant homeostasis by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. : Overall, Under the current experimental conditions, 38% dietary protein is suitable for promoting growth performance, improving protein and lipid metabolism, and enhancing antioxidant homeostasis in black carp.
Lipoprotein(a) Reflects Baseline Lipid Phenotype but Does Not Predict Long-Term Cardiometabolic Risk in Apparently Healthy Women.
Yoon S, Kang M, Yang HS
Metabolites · 2026 Jun · PMID 42346370 · Full text
BACKGROUND/OBJECTIVES: Lipoprotein(a) [Lp(a)] is an established risk-enhancing biomarker for atherosclerotic cardiovascular disease (ASCVD) and is increasingly incorporated into preventive risk assessment. However, wheth...
BACKGROUND/OBJECTIVES: Lipoprotein(a) [Lp(a)] is an established risk-enhancing biomarker for atherosclerotic cardiovascular disease (ASCVD) and is increasingly incorporated into preventive risk assessment. However, whether Lp(a) predicts long-term cardiometabolic disease (CMD) beyond its associations with lipid parameters in apparently healthy women remains unclear. METHODS: We retrospectively analyzed 559 women (median age 41 [36-46] years) who underwent comprehensive health check-ups with baseline Lp(a) measurements. After excluding those with baseline CMD, ASCVD, or insufficient follow-up, 387 women formed the primary longitudinal cohort. Participants were stratified by Lp(a) level (<50 vs. ≥50 mg/dL). Incident composite CMD, defined as new-onset hypertension, diabetes mellitus, or dyslipidemia, was assessed using Kaplan-Meier analysis, Cox proportional hazards models, and sensitivity analyses treating Lp(a) as a continuous variable and restricting the analysis to participants with ≥10 years of follow-up. RESULTS: At baseline, elevated Lp(a) (≥50 mg/dL) was associated with higher total cholesterol and LDL-C and a greater prevalence of dyslipidemia, with a modest Lp(a)-LDL-C correlation (ρ = 0.24, < 0.001). Over a median follow-up of 12.6 years, CMD incidence did not differ between Lp(a) groups (33.3% vs. 35.3%, = 0.907). Lp(a) was not associated with incident CMD in multivariable Cox models (adjusted HR 0.81, 95% CI 0.49-1.34), with consistent findings in the ≥10-year follow-up subgroup ( = 224) and in continuous-variable sensitivity analyses. CONCLUSIONS: In apparently healthy women, elevated Lp(a) reflects an adverse baseline lipid phenotype but does not independently predict long-term incident CMD. These findings suggest that the clinical utility of Lp(a) may be context-dependent, with its predictive value primarily limited to ASCVD risk assessment rather than broader cardiometabolic risk prediction in this population.
Metabolism and Yield of Grape-Tomato Hybrids Under Heat Stress in an Innovative Protected Environment Using Twin-Walled Polycarbonates with Laminar Water Flow.
Garcia RR, Nunes A, Pedrosa Junior JAP … +8 more , Campos RADS, Ponce FDS, Ramsay JOM, Zanuzo MR, de Souza SGH, Fernandes Junior F, Botelho SCC, Junior SS
Metabolites · 2026 Jun · PMID 42346369 · Full text
: The high temperatures associated with climate change represent an important constraint for tomato production in tropical regions, affecting plant growth, reproductive development, and fruit metabolic composition. In th...
: The high temperatures associated with climate change represent an important constraint for tomato production in tropical regions, affecting plant growth, reproductive development, and fruit metabolic composition. In this context, protected cultivation systems capable of modifying greenhouse microclimates may help reduce thermal stress and maintain crop productivity. : This study evaluated the effects of two protective environments, diffuse agricultural film (AF) and twin-walled polycarbonate panels with laminar water flow (P), on the agronomic performance and fruit metabolic traits of five grape-tomato hybrids grown under tropical conditions. Microclimatic variables, vegetative growth, yield components, postharvest behavior, and fruit quality attributes were evaluated, with emphasis on carotenoid accumulation. : Compared with the agricultural film environment, the polycarbonate system reduced global radiation and photosynthetically active radiation (PAR) and was associated with an increase in yield of approximately 25%, an increase in fruit number of approximately 13%, and an 8% increase in fruit diameter. In addition, some hybrids cultivated under the polycarbonate system showed greater lycopene and β-carotene accumulation, indicating that microclimate moderation may favor carotenoid-related fruit quality depending on genotype. Principal component analysis revealed a clear separation between cultivation environments, with the polycarbonate system more closely associated with yield-related and canopy development traits, whereas the agricultural film environment was linked to biomass accumulation and selected physicochemical attributes. Among the evaluated hybrids, BS IGR0104, Jacy, and GI7545 showed the most favorable combination of agronomic performance and fruit quality traits. : These results demonstrate the importance of climate-adaptive protected cultivation systems and hybrid selection for improving tomato productivity under tropical heat conditions.
Rapid LC-MS/MS Method for Targeted Assay of Creatine Deficiency Syndromes in Morocco.
Meiouet F, Boemer F
Metabolites · 2026 Jun · PMID 42346368 · Full text
Creatine deficiency syndromes (CDS) are rare neurometabolic disorders caused by defects in creatine biosynthesis (AGAT and GAMT deficiencies) or creatine transport (SLC6A8 deficiency). Early biochemical recognition is cr...
Creatine deficiency syndromes (CDS) are rare neurometabolic disorders caused by defects in creatine biosynthesis (AGAT and GAMT deficiencies) or creatine transport (SLC6A8 deficiency). Early biochemical recognition is crucial for timely treatment of AGAT and GAMT deficiencies and for improving neurodevelopmental outcomes. In Morocco, expanding the liquid chromatography-tandem mass spectrometry (LC-MS/MS) biomarker panel for inherited metabolic disorders is a priority to strengthen diagnostic capacity and reduce diagnostic delay. We developed and validated a rapid LC-MS/MS method for the simultaneous quantification of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn) in plasma and urine using isotopically labelled internal standards and a standardized sample preparation procedure. Analytical performance, including linearity, precision, accuracy, sensitivity, matrix effects, carryover, inter-sample contamination, stability, and measurement uncertainty, was assessed in accordance with ISO 15189:2022 requirements. The assay showed excellent linearity across the analytical range (r > 0.99), with robust intra- and inter-day precision (CV < 10%). Limits of detection (LOD) were 0.05 µmol/L for Cr and 0.03 µmol/L for GAA in urine, and 0.05 µmol/L for Cr and GAA in plasma. The total run time was 1.1 min per sample, supporting high-throughput implementation. Method performance was further supported by satisfactory results in ERNDIM external quality assessment schemes. Preliminary internal reference ranges and expanded measurement uncertainty were calculated from the available anonymized dataset. This rapid LC-MS/MS method enables the measurement of key CDS biomarkers and contributes to expanding the LC-MS/MS biomarker panel for inherited metabolic disorders in Morocco.
Effect of Replacing Soybean Meal with Cottonseed Meal or Rapeseed Meal on Growth Performance, Meat Quality, and Metabolome of Raw and Cooked Meat in Finishing Lambs.
Wang S, Zhao X, Wu W … +4 more , Xin G, Chen X, Ghaffari MH, Ma T
Metabolites · 2026 Jun · PMID 42346367 · Full text
OBJECTIVES: To evaluate the effects of replacing soybean meal (SBM) with rapeseed meal (RSM) or cottonseed meal (CSM) in finishing lamb diets on meat, untargeted metabolomics were used to explore underlying mechanisms of...
OBJECTIVES: To evaluate the effects of replacing soybean meal (SBM) with rapeseed meal (RSM) or cottonseed meal (CSM) in finishing lamb diets on meat, untargeted metabolomics were used to explore underlying mechanisms of metabolites related to Volatile Organic Compounds (VOCs) between raw and cooked meat. METHODS: Twenty-four lambs were fed isocaloric and isonitrogenous diets for 90 days and longissimus thoracic (LT) meat was sampled for quality evaluation. RESULTS: Results showed that growth performance and most traits of meat were unaffected, including feed intake, average daily growth, pH, cooking loss, shear force, most color values, and fatty acids. However, the yellowness (b*) in RSM and CSM meat, as well as Met and Tyr in CSM meat, were increased. Muscle metabolomics identified five different metabolite-associated flavor precursors that varied, including galactose, L-pyrdosine, and 13-octadecenoic acid. In total, 223 VOCs detected in cooked meat showed no major differences among diets. Key flavor compounds, including 1-octen-3-ol and lipid-derived aldehydes, were consistent across treatments. CONCLUSIONS: In conclusion, RSM and CSM are viable SBM alternatives, changes in raw meat metabolites do not alter the volatile compounds of cooked meat.
Metabolomic Profiling of Extracellular Vesicles from Flower and Leaf Tissues of .
Hu J, Peng S, Zhou S … +4 more , Zeng Z, Wang S, Guo Z, Chen Y
Metabolites · 2026 Jun · PMID 42346366 · Full text
Plant extracellular vesicles (EVs) mediate intercellular communication and carry tissue-specific metabolites, yet tissue-resolved EV metabolomics in non-model medicinal plants remains poorly explored. is a valuable medi...
Plant extracellular vesicles (EVs) mediate intercellular communication and carry tissue-specific metabolites, yet tissue-resolved EV metabolomics in non-model medicinal plants remains poorly explored. is a valuable medicinal and ornamental species rich in bioactive compounds, but the metabolic profiles of flower- and leaf-derived EVs are unknown. This study aimed to characterize tissue-specific EV metabolomes of and reveal their functional implications. EVs were isolated from flowers (MJH) and leaves (MJY) of and verified by TEM and DLS. Untargeted LC-MS/MS metabolomics was applied to profile EV metabolites. Multivariate statistics (PCA, OPLS-DA), differential metabolite screening (VIP > 1, < 0.05), and KEGG pathway enrichment were performed. MJH- and MJY-EVs exhibited typical EV morphology and high purity. In total, 3338 metabolites were identified, dominated by lipids (29.43%). Clear metabolic separation was observed between MJH- and MJY-EVs. Thirty-nine differential metabolites were identified: 31 upregulated in MJH-EVs (lipids, pentadecanoic acid) and eight in MJY-EVs (nucleotides, secondary metabolites). Glycerophospholipid metabolism was the most enriched pathway in MJH-EVs, while MJY-EVs were linked to energy and defensive metabolism. EVs display strong tissue-specific metabolic signatures. Leaf EVs prioritize lipid metabolism for photosynthetic function and stress tolerance, while flower EVs accumulate secondary and energy-related metabolites for reproduction and defense. These findings advance plant EV biology and support potential applications of EVs in cosmetics and agriculture.
Screening of "Cry for Help" Signals from Induced by and Their Potential for Biological Control.
Xie T, Ding Q, Yang L … +4 more , Wang J, Wei J, Du X, Jin L
Metabolites · 2026 Jun · PMID 42346365 · Full text
BACKGROUND: Root rot caused by is a devastating disease in (danggui), leading to severe yield and quality losses. Sustainable control strategies are urgently needed. According to the plant "cry for help" theory, plants...
BACKGROUND: Root rot caused by is a devastating disease in (danggui), leading to severe yield and quality losses. Sustainable control strategies are urgently needed. According to the plant "cry for help" theory, plants under pathogen attack may recruit beneficial microbes via root exudates. However, whether employs this strategy against remains unknown. This study aimed to identify potential "cry for help" metabolites and evaluate their biocontrol potential. METHODS: LC-MS analysis revealed that infection significantly altered the metabolic profiles of both roots and rhizosphere soil. RESULTS: Comparative analysis identified seven metabolites specifically upregulated in infected plants but not detected in the pathogen, including taurine, oxoadipic acid, quinolinic acid, 6-phosphogluconic acid, methyl cinnamate, 2-phenylethanol, and (R)-3-hydroxybutyric acid. Exogenous application of these seven metabolites revealed that taurine and methyl cinnamate significantly alleviated disease symptoms, improved plant growth (root length, biomass), and enhanced the activities of key defense enzymes (peroxidase, POD, phenylalanine ammonia-lyase, PAL, lipoxygenase, LOX, polyphenol oxidase, PPO). Furthermore, taurine and methyl cinnamate reshaped the rhizosphere microbiome. The incidence of root rot was reduced by 51.3% and 50.8%, respectively. Taurine enriched (e.g., ) and reduced the relative abundance of pathogenic fungi, while methyl cinnamate markedly enriched the nitrogen-fixing bacterium and the saprophytic fungus . Crucially, both treatments significantly suppressed the proliferation of in the rhizosphere. CONCLUSIONS: Our findings demonstrate for the first time that activates a "cry for help" response upon attack by , with taurine and methyl cinnamate preliminarily identified as key signaling metabolites that can directly or indirectly inhibit the development of root rot. These compounds enhance plant resistance and recruit beneficial microorganisms, offering a novel and promising ecological strategy for the green control of root rot.
Effect of Icosa-11,14,17-Trienoic Acid from Oil on Lipogenesis and Adipose Inflammation on Mice with High Fat Diet Induced Obesity.
Panchali T, Kar R, Das P … +4 more , Dutta A, Phoujdar M, Ghosh K, Pradhan S
Metabolites · 2026 Jun · PMID 42346364 · Full text
: Obesity is a complex disease involving the accumulation of an excessive amount of body fat. It is a condition that develops when energy intake and expenditure are out of balance. Inflammation and hypertrophy are caused...
: Obesity is a complex disease involving the accumulation of an excessive amount of body fat. It is a condition that develops when energy intake and expenditure are out of balance. Inflammation and hypertrophy are caused by the storage of too much white adipose tissue, resulting in adiposity, which also secretes several pro-inflammatory cytokines. Several marketed drugs used to treat obesity have many side effects from long-term ingestion. Other therapeutic compounds from marine sources have already been established for treating obesity. In this paper, the main aim is to establish the anti-obesity effect of derived omega-3 fatty acids, i.e., 20:3(n-3)11-14-17 Icosa Trienoic Acid from oil. : In the present investigation, inbred male Swiss albino mice were segregated into six categories as Control, Positive Control, Obese Control, and 20:3(n-3)11-14-17 Icosa Trienoic Acid treated groups with three different doses: Treatment 1, Treatment 2 and Treatment 3. To establish the potentiality of extracted fatty acid, different parameters would be considered, such as body weight, lipid composition and different obesity and obesity-associated inflammation markers. : After the isolated compound from oil was applied to the treated mice group, it decreased their body weight and serum lipid profile by 39.05%, 62.69%, 62.72%, and 78.46% compared to obese mice. They also had lower levels of uric acid, Serum Glutamic-Oxaloacetic Transaminase, Serum Glutamic Pyruvic Transaminase, and Alkaline Phosphatase, at 67.52%, 57.09%, 64.80%, and 43.99%, than the obese group. Accordingly, the treated group's expression of genes linked to obesity and pro-inflammatory cytokines was downregulated. The isolated compound affected both anti-inflammatory and anti-obesity markers' increased expression. : After the experiments, it was found that the possibility of using fatty acids might be helpful as an anti-inflammatory and anti-obesity therapeutic strategy. This therapeutic strategy will be cheap and cost-effective.
Circadian Regulation of Gut Microbial Metabolites in Intestinal Epithelial Homeostasis.
Park M, Kim S, Choe J
Metabolites · 2026 Jun · PMID 42346363 · Full text
The gut microbiota produces chemically diverse metabolites whose levels fluctuate depending on the time of day, driven by bidirectional coupling between host intestinal circadian clocks and intrinsic microbial oscillator...
The gut microbiota produces chemically diverse metabolites whose levels fluctuate depending on the time of day, driven by bidirectional coupling between host intestinal circadian clocks and intrinsic microbial oscillators. Although short-chain fatty acids have received the most attention as microbial circadian effectors, a broad class of metabolites, including secondary bile acids, indole derivatives, and branched-chain fatty acids, engage distinct epithelial receptors and transcriptional programs through mechanisms that are, to varying degrees, subject to circadian regulation. However, the mechanisms by which these metabolite classes collectively regulate barrier integrity, mucosal immune tone, and stem cell-driven renewal, as well as the consequences of their rhythmicity loss under circadian misalignment, have not been systematically reviewed. This review constructs a mechanistic framework linking microbial metabolite rhythmicity to the circadian regulation of intestinal epithelial homeostasis and evaluates dietary and probiotic interventions that modulate this axis as chronobiotic strategies. Convergent mechanisms, unresolved questions, and translational opportunities are identified across in vitro, preclinical, and clinical evidence.
Combinatorial Effects of Boron Compounds on Immunophenotypic Modulation of Mouse Hematopoietic Stem Cell Subsets Ex Vivo.
Kocabaş F, Esendir E, Meriç N
Metabolites · 2026 May · PMID 42346362 · Full text
BACKGROUND/OBJECTIVES: Hematopoietic stem cells (HSCs) sustain lifelong blood cell production and hold therapeutic promise, yet their ex vivo expansion remains constrained by an incomplete understanding of the metabolic...
BACKGROUND/OBJECTIVES: Hematopoietic stem cells (HSCs) sustain lifelong blood cell production and hold therapeutic promise, yet their ex vivo expansion remains constrained by an incomplete understanding of the metabolic and cellular mechanisms governing self-renewal. In this study, we investigated whether boron compounds boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium 2-pentaborate pentahydrate-8 (Na2B8) can promote the expansion of mouse HSCs by modulating key stem cell populations linked to metabolic fitness. METHODS: Lineage-negative (Lin-) cells were magnetically isolated and treated with each boron compound for four days, followed by flow cytometric analysis of c-Kit, Sca-1, Lin-c-Kit+Sca-1+ (LSK), and LSKCD34 HSC-enriched subsets. RESULTS: Our results show that boron derivatives exert distinct effects on these cellular markers. Notably, NaB treatment significantly increased the Lin-Sca-1+ cell fraction, while Na2B8 elevated both LSK and LSKCD34 ratios. Furthermore, the BA+NaB combination produced a statistically significant proliferative effect on Sca-1+ and c-Kit+ (CD117) cells. CONCLUSIONS: These findings indicate that specific boron compounds enhance ex vivo HSC expansion through yet-to-be-defined mechanisms that underpin HSC self-renewal. Further mechanistic studies are warranted to delineate the precise metabolic targets, but these results highlight boron compounds as promising tools for improving HSC expansion strategies.
Chronic Caffeine Consumption Prevents Body Weight Gain and Glucose Intolerance in High-Fat Diet-Induced Obesity Mice Model.
Faraco G, Mendes NF, Schmitt LO … +5 more , Stivanin TS, Gaspar E, Platt N, Kaster MP, Gaspar JM
Metabolites · 2026 May · PMID 42346361 · Full text
: Caffeine consumption has been reported to have beneficial effects in metabolic disorders; however, its effects on food intake are not fully elucidated. This study evaluated the impact of chronic caffeine consumption on...
: Caffeine consumption has been reported to have beneficial effects in metabolic disorders; however, its effects on food intake are not fully elucidated. This study evaluated the impact of chronic caffeine consumption on weight gain, food intake, and metabolic parameters in C57BL/6 male mice. : Eight-week-old male mice (28 animals) were divided into four groups: control (chow diet), caffeine (chow diet + 1 g/L caffeine in drinking water), high-fat diet (HFD), and HFD + caffeine (HFD + 1 g/L caffeine in drinking water). Diets and caffeine were provided ad libitum for 8 weeks. Food and water intake were recorded weekly, and blood glucose was measured every 4 weeks. After 8 weeks of diet and caffeine exposure, metabolic tests were conducted, and tissues were collected for biochemical analysis. : HFD consumption for 8 weeks induced an increase in body weight and adiposity compared to the chow diet, without changes in food intake. Caffeine consumption prevented body weight gain and adiposity, although it increased food intake. Caffeine also improved glucose tolerance in the HFD mouse model, without changes in random blood glucose, triglyceride, or cholesterol levels. Analysis of hypothalamic neuropeptide (Agrp, NPY, Pomc, Cart), involved in the control of food intake, showed no differences in expression. There were also no changes observed in locomotion nor in anxiety-like behavior. : In conclusion, chronic high-fat diet (HFD) exposure induced obesity characterized by increased body weight and adiposity without altering food intake. Chronic caffeine consumption counteracted HFD-induced weight gain and fat accumulation and improved glucose tolerance, despite increasing food intake. Importantly, caffeine consumption in the HFD group did not affect locomotor activity or anxiety-like behavior, suggesting that its metabolic effects are not driven by changes in general activity or emotional state. Overall, these findings indicate that chronic caffeine consumption improves metabolic homeostasis in HFD-fed mice.
The Application of Metabolomics in Frailty: Trends, Challenges, and Future Directions.
Fang K, Niu B, Zhang Z … +3 more , Jiang Y, Zhao Y, Wang Z
Metabolites · 2026 May · PMID 42346360 · Full text
Frailty is a geriatric syndrome involving inflammation, oxidative stress, mitochondrial dysfunction, and metabolic disturbances. Metabolomics can systematically elucidate metabolic pathways and identify actionable biomar...
Frailty is a geriatric syndrome involving inflammation, oxidative stress, mitochondrial dysfunction, and metabolic disturbances. Metabolomics can systematically elucidate metabolic pathways and identify actionable biomarkers. This study systematically reviews the progress and evolutionary trends of metabolomics applications in frailty research from 2006 to 2025. Based on 1924 publications retrieved from the Web of Science Core Collection, systematic analyses were performed using CiteSpace, VOSviewer, SCImago Graphica, and the R package "bibliometrix", focusing on pathway-level research hotspots and collaboration networks. The United States and China are the leading contributors. Research hotspots have shifted from macro-level biomarkers such as inflammation and protein-energy wasting to specific metabolic pathways including amino acid metabolism, energy metabolism, lipid metabolism, and tryptophan degradation. Key metabolites include sphingomyelin, butyrate, and trimethylamine-N-oxide. Emerging frontiers focus on the association between gut microbiota-derived metabolites and frailty phenotypes, as well as intervention strategies targeting these metabolites. This study provides the first systematic overview of global research progress in metabolomics and frailty, establishes a reproducible evaluation framework integrating physiology, nutrition, geriatrics, and computational biology, and identifies butyrate, trimethylamine-N-oxide, and tryptophan metabolites as potential metabolic targets for early identification and intervention.
Relationships Among Adipose Tissue Distribution, Vitamin D, and Bone Metabolism in Normoglycemic and Type 2 Diabetic Individuals.
Ma TH, Zhao J, Zhou KH … +9 more , Guan YX, Zuo F, Nian X, Zheng Y, Wang WJ, Zhang LJ, Kazumi T, Huang J, Wu B
Metabolites · 2026 May · PMID 42346359 · Full text
OBJECTIVES: To investigate the interplay between adipose distribution, vitamin D metabolites, and bone mineral density (BMD) in Normal Glucose Tolerance (NGT) and type 2 Diabetic (T2DM) individuals. METHODS: 167 particip...
OBJECTIVES: To investigate the interplay between adipose distribution, vitamin D metabolites, and bone mineral density (BMD) in Normal Glucose Tolerance (NGT) and type 2 Diabetic (T2DM) individuals. METHODS: 167 participants (NGT: 61; T2DM: 106) were enrolled. Serum 25(OH)D, 1,25(OH)D, Parathyroid Hormone (PTH), and Ca were quantified. Visceral (VAT) and subcutaneous (SAT) adipose areas were assessed via dual bioelectrical impedance analysis. BMD and body composition were assessed via DXA. Metabolic indices (HOMA-IR, HOMA-β, ISI) were calculated. RESULTS: 1. NGT: 25(OH)D was unrelated to adiposity. Conversely, 1,25(OH)D was correlated inversely with VAT, SAT, body mass index (BMI), and Fat Mass Index (FMI), with VAT being the strongest independent predictor. 2. T2DM: High VAT correlated with insulin resistance yet paradoxically higher BMD. 25(OH)D correlated positively with Z-score, while 1,25(OH)D correlated negatively with lumbar BMD. 3. VAT exerted a greater influence on insulin resistance than SAT, particularly in T2DM. CONCLUSIONS: 1. Visceral adiposity is the primary determinant of active 1,25(OH)D metabolism in both NGT and T2DM individuals. 2. 1,25(OH)D levels may be more closely associated with adiposity-related metabolic alterations than 25(OH)D. Despite lower 1,25(OH)D, the positive association between VAT and BMD in T2DM suggests complex mechanisms where visceral fat may paradoxically influence bone metabolism while driving insulin resistance.
Genetically Informed Single-Cell Analysis Reveals as a Cell-Type-Specific Molecular Switch in MASLD.
Ma X, Song J, Hong X … +1 more , Lin Z
Metabolites · 2026 May · PMID 42346358 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder driven by genetic predisposition, epigenetic programming, metabolic rewiring, and immune dysregulation. Although population genetics...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic disorder driven by genetic predisposition, epigenetic programming, metabolic rewiring, and immune dysregulation. Although population genetics and single-cell transcriptomics have advanced our understanding, the multi-omic causal architecture of MASLD at cellular resolution remains poorly defined. This study aimed to establish an integrative framework linking genetic causality to cell-type-specific tissue dysfunction. Multi-layered Mendelian randomization (MR) and summary-data-based MR (SMR) across large-scale eQTL and pQTL datasets were applied to prioritize causal genes. Single-cell eQTL-based MR across 14 immune lineages generated cell-type-specific causal hypotheses, which were validated using human hepatic single-cell RNA-sequencing data (GSE136103). Two-step mediation MR quantified upstream epigenetic and downstream metabolic mechanisms. A high-fat diet (HFD)-induced murine model provided organismal validation. Multi-layered MR nominated as a robust causal driver of MASLD. Single-cell eQTL-based MR revealed a functional dichotomy: upregulation in CD8 effector memory T-cells decreased MASLD risk (OR = 0.486, 95% CI: 0.290-0.813, = 0.006), whereas upregulation in natural killer cells (OR = 1.567, 95% CI: 1.337-1.837, < 0.001), non-classical monocytes, and dendritic cells increased risk. Human hepatic single-cell transcriptomics confirmed that marks an anti-fibrotic, IFNG-high CD8 T subset and a pro-inflammatory lipid-associated macrophage (LAM) population. Mediation MR identified DNA methylation at cg26767922 and cg08471739 as protective mediators acting predominantly via downregulation (92.39% and 64.50% mediation, respectively), and linked to six circulating metabolites. HFD mice showed significant hepatic upregulation. functions as a lineage-dependent molecular switch in MASLD, validated across genetic, epigenetic, metabolic, and single-cell dimensions. These findings caution against systemic blockade and support precision therapeutic strategies targeting hepatic innate immune cells.
Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer's Disease.
Chen J, Chen X, Chen T … +1 more , Hu J
Metabolites · 2026 May · PMID 42346357 · Full text
: Previous metabolomics studies on Alzheimer's disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. : To characterize metabolic alter...
: Previous metabolomics studies on Alzheimer's disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. : To characterize metabolic alterations across different clinical stages of AD in a Chinese population and identify early diagnostic biomarkers. : We enrolled 172 participants, including patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), vascular cognitive impairment (VCI), and healthy controls (HC). Untargeted metabolomics (LC-MS and GC-MS) was performed on plasma samples, integrated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessments. Data were analyzed using multivariate statistics, pathway enrichment, and ROC modeling. Distinct metabolic profiles emerged across disease stages, with phospholipids, ceramides, and glucose metabolites prominently enriched in glycerophospholipid, sphingolipid, and glucose pathways. A 16-metabolite panel achieved robust discrimination between AD+MCI and HC+VCI+SCD (AUC = 0.804). Specific metabolites, including ceramides, dihydroceramides, phosphatidylinositol, phosphatidylcholine, and glycodeoxycholic acid, correlated significantly with cognitive function and disease progression. : This study reveals stage-specific metabolic dysregulation in Chinese AD patients and identifies potential plasma biomarkers for early detection, offering insights into AD pathogenesis. Trial registration number ChiCTR2400092653.
Ameliorates Sleep Deprivation-Induced Ileal Mucus Barrier Dysfunction by Regulating Steroid Hormone Biosynthesis and the HPA Axis in Rats.
Luo X, Jin S, Fang Y … +3 more , Zhao Q, Xie H, Han L
Metabolites · 2026 May · PMID 42346356 · Full text
: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Ch...
: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. : The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic-pituitary-adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). : DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis. : In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation.
Transcriptome and Metabolome Analyses Reveal the Molecular Relationship Between Dietary Crude Protein Level and Liver Metabolism in Fattening Hu Sheep.
Abudukeyimu P, Xie F, Hu Y … +5 more , He H, Hou C, Sulaiman Y, Yang H, Gong G
Metabolites · 2026 May · PMID 42346355 · Full text
Dietary crude protein (CP) acts as a key nutritional factor that affects the growth performance and liver metabolism of fattening Hu sheep, with metabolizable energy (ME) representing a major confounding factor in CP-rel...
Dietary crude protein (CP) acts as a key nutritional factor that affects the growth performance and liver metabolism of fattening Hu sheep, with metabolizable energy (ME) representing a major confounding factor in CP-related responses. To isolate the specific effects of CP on liver metabolism and minimize energy-protein interactions, we standardized dietary ME at 9.4 MJ/kg dry matter. We then established three isoenergetic CP concentrations: 11.07%, 13.07%, and 15.11%. A total of ninety 4-month-old male Hu sheep (with an initial body weight of 27.09 ± 1.83 kg) were allocated at random to three dietary treatment groups, each containing 30 animals distributed across three replicate pens, and fed pelleted total mixed rations (PTMRs) for 75 days under pen conditions in southern Xinjiang. Exploratory combined transcriptomic and metabolomic profiling of liver tissue was conducted to characterize how graded CP levels modulate growth traits and hepatic metabolic pathways, thereby identifying the appropriate dietary CP level for efficient and sustainable fattening of Hu sheep in this region. Results indicated that animals fed the 15.11% CP diet showed a significantly higher average daily gain (ADG) and cumulative weight gain compared with those fed 11.07% or 13.07% CP ( < 0.05). Exploratory multi-omics enrichment analysis demonstrated significant overrepresentation ( < 0.05) of differentially expressed genes and metabolites in key biological pathways-including bile secretion, AMP-activated protein kinase (AMPK) signaling, steroid biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling, and oxidative stress-related and oxidative phosphorylation. Correlation analyses characterized two hub genes-ATP6AP1 and LOC101119853-that were significantly and negatively correlated with ADG ( < 0.05), whereas two metabolites-calcidiol and ADP-displayed significant positive relationships with ADG ( < 0.05). Pathway-level comparisons further demonstrated that both the 13.07% vs. 15.11% CP and the 11.07% vs. 15.11% CP contrasts yielded significant enrichment in AMPK signaling and steroid biosynthesis. Notably, calcidiol and ADP both declined numerically in the 13.07% vs. 15.11% CP comparison, whereas only ADP reached statistical significance in the 11.07% vs. 15.11% CP contrast. Collectively, under an ME level of 9.4 MJ/kg, a dietary CP concentration of 15.11% contributes to favorable growth of 4-month-old fattening Hu sheep housed in pens in southern Xinjiang. This level is associated with improved growth performance and coordinated regulation of central hepatic regulatory networks-particularly those involved in energy homeostasis and steroidogenesis-thereby supporting metabolic stability without compromising animal health or production efficiency. These findings provide a preliminary molecular basis for precision protein nutrition in Hu sheep feeding systems and offer translational insights for optimizing ruminant nutrition under arid and semi-arid environmental constraints. All correlations indicate potential associations, not causal relationships.
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