MetabolitesPub Date : 2026-04-21DOI: 10.3390/metabo16040285
Liang Zhang, Wenxin Wang, Fengting Zheng, Jialu Weng, Yao Lu, Qingbo Li, Ting Li, Wei Li, Lifeng Wang
{"title":"Aerobic Exercise Alleviates Oxidative Stress and Inflammation to Attenuate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in <i>ApoE<sup>-/-</sup></i> Mice.","authors":"Liang Zhang, Wenxin Wang, Fengting Zheng, Jialu Weng, Yao Lu, Qingbo Li, Ting Li, Wei Li, Lifeng Wang","doi":"10.3390/metabo16040285","DOIUrl":"https://doi.org/10.3390/metabo16040285","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The development of non-alcoholic fatty liver disease (NAFLD) is closely linked to oxidative stress and inflammation. Aerobic exercise has been shown to improve NAFLD, although its underlying mechanisms remain incompletely understood. This study utilized <i>ApoE<sup>-/-</sup></i> mice to investigate the role of Sestrin2 in aerobic exercise-induced amelioration of NAFLD. <b>Methods</b>: Random assignment of C57BL/6J and <i>ApoE</i><sup>-/-</sup> mice yielded four groups: C (control), CE (aerobic exercise), AS (<i>ApoE<sup>-/-</sup></i> control), and AE (<i>ApoE<sup>-/-</sup></i> aerobic exercise). Aerobic exercise lasting 12 weeks was administered to the CE and AE groups. Serum biomarkers were analyzed by ELISA, liver tissue morphology was assessed via HE and ORO staining, and macrophage polarization was evaluated through immunofluorescence. Additionally, mRNA and protein expression levels were measured by qPCR and Western blot. <b>Results</b>: Aerobic exercise reduced liver wet weight, lipid accumulation, and steatosis in <i>ApoE<sup>-/-</sup></i> mice. Aerobic exercise attenuates hepatic oxidative stress, and upregulated the expression of regulation oxidative stress related gene and proteins of Nrf2, HO-1, CAT, and SOD1 in <i>ApoE<sup>-/-</sup></i> mice. Aerobic exercise promoted a shift in macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype in the liver, and significantly reduced TNF-α and IL-1β levels, accompanied by upregulation of Sestrin2 expression, enhanced AMPK phosphorylation, inhibited mTORC1 in the liver. <b>Conclusions</b>: These findings suggest that aerobic exercise alleviates oxidative stress and inflammation in NAFLD, with Sestrin2 activation playing a central role.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-21DOI: 10.3390/metabo16040284
Saif A Alqahtani, Hanan H Alshehri, Hend Ashour, Hend Abdallah, Laila Rashed, Rehab M Badi, Muataz E D Mohammed, Bahjat Al-Ani, Norah M Alzamil, Alia Albawardi, Basma E Aboulhoda
{"title":"Quercetin Attenuates Non-Alcoholic Fatty Liver Disease in Association with the Inhibition of Hepatic IL-1β/iNOS and IL-1β/CD45 Axes of Inflammation and Fibrosis Accompanied by Reduced Endogenous Metabolites and Apoptosis.","authors":"Saif A Alqahtani, Hanan H Alshehri, Hend Ashour, Hend Abdallah, Laila Rashed, Rehab M Badi, Muataz E D Mohammed, Bahjat Al-Ani, Norah M Alzamil, Alia Albawardi, Basma E Aboulhoda","doi":"10.3390/metabo16040284","DOIUrl":"https://doi.org/10.3390/metabo16040284","url":null,"abstract":"<p><strong>Background: </strong>Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin.</p><p><strong>Methods: </strong>The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29.</p><p><strong>Results: </strong>NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt's NASH classification). All these parameters were significantly (<i>p</i> < 0.01) modulated by quercetin treatment. Additionally, a significant (<i>p</i> < 0.001) correlation between IL-1β and hepatic injury parameters was observed.</p><p><strong>Conclusions: </strong>These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-20DOI: 10.3390/metabo16040279
Zhiyong Li, Jian Li, Yue Hu, Xinyi Wu, Xiaojuan Duan, Demin Kong, Xiaowen Li, Jin Cheng, Meina Wang
{"title":"Metabolomic Profiling Reveals Geographical Origin, Tissue-Specific Specialization, and Environmental Plasticity in Secondary Metabolism of <i>Dendrobium officinale</i>.","authors":"Zhiyong Li, Jian Li, Yue Hu, Xinyi Wu, Xiaojuan Duan, Demin Kong, Xiaowen Li, Jin Cheng, Meina Wang","doi":"10.3390/metabo16040279","DOIUrl":"https://doi.org/10.3390/metabo16040279","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Dendrobium officinale</i> (<i>D. officinale</i>), an endangered ornamental and medicinal orchid, displays significant variability in its bioactive compounds depending on geographical and environmental factors. To decipher these influences, we investigated metabolic divergence across three cultivars (GN, LS, DX) cultivated in greenhouse and outdoor conditions using untargeted metabolomics. <b>Methods</b>: Metabolites extracted from stem and leaf tissues were analyzed via UHPLC-Q Exactive Orbitrap MS, and the raw data were processed using XCMS for peak alignment and quantification. Differentially abundant metabolites (DAMs) were identified by multivariate statistical analyses including PCA and OPLS-DA. Metabolic pathways were annotated using KEGG, HMDB, and LIPID Maps databases, with enrichment analysis and visualization performed via TBtools II and Hiplot. <b>Results</b>: Metabolite profiling and multivariate analysis revealed distinct chemotypes. The DX cultivar exhibited anthocyanin enrichment in its stems, correlating with a red pigmentation, while GN accumulated specific amino acid derivatives. Tissue-specific metabolic specialization was evident, with leaves displaying greater flavonoid diversity and stems prioritizing lipid and amino acid metabolism. Outdoor cultivation enhanced flavonoid biosynthesis, whereas greenhouse conditions favored alkaloid accumulation. Functional analysis identified both conserved pathways, like phenylpropanoid biosynthesis, and varietal-specific adaptations in amino acid and secondary metabolism. Notably, alkaloid levels declined sharply during plant defoliation. <b>Conclusions</b>: Our findings demonstrate that environmental factors and geographical origin synergistically shape the metabolic profiles of <i>D. officinale</i>. This provides a scientific basis for optimizing cultivation strategies-through targeted environmental adjustments and varietal selection-to enhance the yield of desired bioactive compounds.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-20DOI: 10.3390/metabo16040282
Yufan Si, Wei Li, Yang Chen, Jiayang Yuan, Chenrui Hu, Yanan Liu, Li Li
{"title":"Critical Role for Malic Enzymes in MYC-Mediated Cellular Adaptation to Glutamine Depletion.","authors":"Yufan Si, Wei Li, Yang Chen, Jiayang Yuan, Chenrui Hu, Yanan Liu, Li Li","doi":"10.3390/metabo16040282","DOIUrl":"https://doi.org/10.3390/metabo16040282","url":null,"abstract":"<p><p><b>Background/Objectives:</b> MYC-driven tumors exhibit significant glutamine addiction, but the metabolic adaptation mechanisms enabling their survival under glutamine deprivation remain incompletely understood. Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate while generating NADPH, linking central carbon metabolism to redox homeostasis. This study investigates whether and how ME1 and ME2 mediate cell adaptation to glutamine starvation and explores their functional division in relation to p53 status. <b>Methods:</b> Using MYC-amplified, p53-mutant (G266E) SF188 glioblastoma cells, we performed siRNA-mediated knockdown, overexpression, and rescue experiments. Cell survival was assessed by trypan blue exclusion and Annexin V/PI staining. ROS levels and NADP<sup>+</sup>/NADPH ratios were measured by DCFH-DA fluorescence and enzymatic assays. Metabolite tracing was conducted using [U-<sup>13</sup>C<sub>5</sub>] glutamine followed by LC-MS. Key findings were validated in additional cell lines including HCT116, U2OS and MDA-MB-231. <b>Results:</b> ME1 and ME2 promote SF188 cell survival under glutamine deprivation, an effect that depends on their catalytic activity but is independent of TCA cycle anaplerosis. ME1 maintains redox balance by generating NADPH, and antioxidant treatment rescues the survival defect caused by ME1 knockdown. In contrast, ME2 does not contribute to redox regulation but stabilizes mutant p53 (G266E) via proteasome inhibition. Both of these pro-survival functions are attenuated upon MYC knockdown, suggesting a dependency on MYC expression. Across all cell lines tested, ME1 and ME2 also promote survival through redox maintenance, although the isoform responsible for antioxidant function differs. <b>Conclusions:</b> ME1 and ME2 support metabolic adaptation to glutamine starvation through distinct, isoform-specific mechanisms that depend on MYC expression and p53 mutation status. These findings suggest malic enzymes as potential therapeutic targets in MYC-driven, p53-mutant tumors.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-20DOI: 10.3390/metabo16040280
Anastasios Zagaliotis, Athanasios Roumeliotis, Stefanos Roumeliotis, Ioannis E Neofytou, Garyfallia Varouktsi, Eirini Leptokaridou-Mourtzila, Aikaterini Stamou, Vasiliki Sgouropoulou, Gordana Kocic, Andrej Veljkovic, Rudolf Bittner, Willi Jahnen-Dechent, Leon J Schurgers, Vassilios Liakopoulos
{"title":"Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio as Markers of Cardiovascular Disease and Vascular Calcification in Chronic Kidney Disease: A Large Cohort Study.","authors":"Anastasios Zagaliotis, Athanasios Roumeliotis, Stefanos Roumeliotis, Ioannis E Neofytou, Garyfallia Varouktsi, Eirini Leptokaridou-Mourtzila, Aikaterini Stamou, Vasiliki Sgouropoulou, Gordana Kocic, Andrej Veljkovic, Rudolf Bittner, Willi Jahnen-Dechent, Leon J Schurgers, Vassilios Liakopoulos","doi":"10.3390/metabo16040280","DOIUrl":"https://doi.org/10.3390/metabo16040280","url":null,"abstract":"<p><strong>Background/objectives: </strong>Cardiovascular disease (CVD) in chronic kidney disease (CKD) arises from a multifaceted interplay of pathophysiological processes, including chronic inflammation, oxidative stress (OS), and accelerated vascular calcification (VC). Red blood cell distribution width (RDW) and the neutrophil-to-lymphocyte ratio (NLR) have emerged as simple, inexpensive, and readily available hematological indices that may capture these underlying disturbances. As such, they hold promise as accessible biomarkers for stratifying cardiovascular risk in patients with CKD.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 497 patients, comprising 477 with CKD across all stages and 20 controls. We evaluated the associations of RDW and NLR with both traditional and non-traditional cardiovascular risk factors, as well as with serum calcification propensity (T50). Spearman's correlation and multivariable regression analysis were used to assess these relationships.</p><p><strong>Results: </strong>Both RDW and NLR were significantly elevated in patients with established CVD (<i>p</i> < 0.001 for both) and demonstrated a progressive increase across advancing CKD stages (<i>p</i> < 0.001). RDW and NLR showed positive correlations with age, CVD duration, urea, phosphorus, parathormone, CRP, FG23, and mean carotid intima-media thickness (cIMT), while exhibiting inverse correlations with eGFR, serum albumin, hemoglobin, lipids, antioxidants such as superoxide dismutase, fetuin-A, and T50. Additionally, NLR correlated positively with the duration of hypertension and diabetes, as well as with albuminuria. Quartile analysis revealed a stepwise decline in T50 across increasing categories of RDW and NLR, supporting the link with impaired calcification defense. In multivariable analysis, T50 independently predicted NLR (β = -0.013; <i>p</i> = 0.018), whereas total cholesterol (β = -0.011; <i>p</i> = 0.019) and cIMT (β = 0.38; <i>p</i> = 0.018) emerged as independent determinants of RDW.</p><p><strong>Conclusions: </strong>RDW and NLR strongly reflect the burden of inflammation, metabolic disturbance, and vascular dysfunction in patients across the CKD spectrum. The consistent associations with impaired calcification defense and with established cardiovascular risk markers underscore the potential value as accessible indicators of cardiovascular vulnerability in CKD. These findings support incorporating RDW and NLR into routine risk assessment and highlight T50 as a mechanistically relevant determinant of hematologic inflammation profiles.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-20DOI: 10.3390/metabo16040283
Oluteru E Orimaye, Paul C Omaliko, Nathanael I Lichti, Bruce R Cooper, Yewande O Fasina
{"title":"Comparative Analysis of Two Dietary Saturated Fat Types on Metabolite Profiles Crossing the Blood-Brain Barrier of Poultry Chicks.","authors":"Oluteru E Orimaye, Paul C Omaliko, Nathanael I Lichti, Bruce R Cooper, Yewande O Fasina","doi":"10.3390/metabo16040283","DOIUrl":"https://doi.org/10.3390/metabo16040283","url":null,"abstract":"<p><p><b>Background:</b> The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty acids, is rapidly absorbed without re-esterification. <b>Methods:</b> Day-old broilers (Ross 708 male, n = 160) were distributed into two dietary treatments with five replicates of 16 birds each. The birds were fed a corn-soybean meal (SBM) basal diet supplemented with 3% of poultry fat (CON) or coconut oil (COCO). The body-weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were recorded over a 3-week period, and the data were subjected to a <i>t</i>-test. Untargeted metabolomic analysis by high-performance liquid chromatography (HPLC-MS) was used to evaluate the influence of the type of dietary fat on metabolite profiles in the DRN, HYP, and plasma of broiler chickens. Principal component analysis (PCA) was used to identify unique metabolites, and ANOVA was used to identify the metabolites that were significantly abundant (<i>p</i> < 0.05). The metabolites were then annotated using the KEGG and HMDB databases. <b>Results:</b> Birds in the COCO treatment gained more weight on average (0.8446 kg/bird) than birds in the CON group (0.8132 kg/bird; <i>p</i> = 0.0496). Five metabolites associated with multiple significant cellular processes, such as brain function, energy metabolism, and neurotransmission, showed similar differential expression patterns, while two metabolic pathways (butanoate metabolism and alanine, aspartate and glutamate metabolism) were identified. <b>Conclusions:</b> The dietary inclusion of COCO improves BWG in poultry and enhances their overall well-being by modulating metabolite profiles, supporting neurotransmission, and enriching the metabolic pathways essential for growth and brain function.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-20DOI: 10.3390/metabo16040281
Ewa Zmysłowska-Polakowska, Tomasz Płoszaj, Sebastian Skoczylas, Julia Grzybowska-Adamowicz, Dobromiła Barańska, Katarzyna Matera, Aleksandra Palatyńska-Ulatowska, Wojciech Młynarski, Agnieszka Zmysłowska, Michal Ciborowski
{"title":"Selected Brain Metabolites and Mitochondrial DNA Copy Number as Potential Markers of Ongoing Neurodegeneration in Patients with Wolfram Syndrome.","authors":"Ewa Zmysłowska-Polakowska, Tomasz Płoszaj, Sebastian Skoczylas, Julia Grzybowska-Adamowicz, Dobromiła Barańska, Katarzyna Matera, Aleksandra Palatyńska-Ulatowska, Wojciech Młynarski, Agnieszka Zmysłowska, Michal Ciborowski","doi":"10.3390/metabo16040281","DOIUrl":"https://doi.org/10.3390/metabo16040281","url":null,"abstract":"<p><p><b>Background</b>: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mellitus, subsequent symptoms are associated with optic nerve atrophy, followed by central nervous system atrophy. <b>Methods</b>: The aim of the study was to analyse magnetic resonance images (MRI) of the brain in combination with single-voxel magnetic resonance spectroscopy (MRS) and to assess the copy number of mitochondrial DNA (mtDNA-CN) in 10 patients with WFS compared with a control group of 17 healthy individuals. <b>Results</b>: A significant decrease in the amount of selected metabolites was observed in WFS patients compared to controls in all assessed brain regions (pons, cerebellum, white matter, thalamus, and hippocampus). For three metabolites, Glutamate (Glu), Glutamate + Glutamine (Glx) and total N-acetylaspartate (TNAA), significant differences in concentrations were found between the study groups in almost all matrices evaluating specific areas of the brain (<i>p</i> < 0.011), with the exception of a trend toward reduced TNAA in the hippocampus (<i>p</i> = 0.065). In addition, patients with WFS had a significant decrease in the mitochondrial-to-nuclear DNA ratio compared to controls (<i>p</i> < 0.0003). Some metabolites, such as N-acetylaspartate and total N-acetylaspartate, showed strong correlations with specific regions of the visual pathway on MRI scans in patients with WFS. <b>Conclusions</b>: Selected brain metabolites and mtDNA-CN may become potential markers of WFS, and the results of this study may be used to define indicators for future therapeutic strategies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-19DOI: 10.3390/metabo16040277
María de Los Angeles Cepero-González, Adriana Aguilar-Galarza, Víctor Manuel Rodríguez-García, Teresa García-Gasca, Ulisses Moreno Celis
{"title":"Diagnostic Criteria and Genetic Basis of Polycystic Ovary Syndrome: A Narrative Review.","authors":"María de Los Angeles Cepero-González, Adriana Aguilar-Galarza, Víctor Manuel Rodríguez-García, Teresa García-Gasca, Ulisses Moreno Celis","doi":"10.3390/metabo16040277","DOIUrl":"https://doi.org/10.3390/metabo16040277","url":null,"abstract":"<p><p>This study reviews the main candidate genes involved in the pathophysiology of Polycystic Ovary Syndrome (PCOS). PCOS is a common endocrine-metabolic disorder in women of reproductive age, characterized by menstrual irregularity, hyperandrogenism, and polycystic ovarian morphology. It is associated with increased metabolic and cardiovascular risk and is a leading cause of infertility. Although its pathophysiology is not fully understood, alterations in the hypothalamic-pituitary-ovarian axis, insulin metabolism, and steroidogenesis have been described. Polymorphisms in genes encoding hormones, enzymes, and receptors in these pathways contribute to clinical variability and ethnic differences, offering potential for early diagnosis and personalized medicine. This review summarizes key candidate genes related to insulin metabolism (INS, INSR, IRS-1), the hypothalamic-pituitary-ovarian axis (LHβ, LHCGR, FSHR, GnRHR, AMH, AMHR2, KISS1, CAPN10), steroidogenesis (CYP11A, CYP17A1, CYP19A1, CYP21, 17β-HSD, SHBG, AR, STAR), and other clinically relevant mechanisms such as obesity, lipid metabolism (PPARG, VDR, FTO), and follicular development (ACE).</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-19DOI: 10.3390/metabo16040278
Tomiko Kuhara, Morimasa Ohse, Tatsuya Fukasawa, Koichi Maruyama, James Pitt
{"title":"Identification of Primary Hyperoxaluria Type III by Gas Chromatography/Mass Spectrometry-Based Urine Metabolomics.","authors":"Tomiko Kuhara, Morimasa Ohse, Tatsuya Fukasawa, Koichi Maruyama, James Pitt","doi":"10.3390/metabo16040278","DOIUrl":"https://doi.org/10.3390/metabo16040278","url":null,"abstract":"<p><p><b>Objectives:</b> Primary hyperoxaluria type III (PH3) causes kidney stones in children and adults. Gas chromatography/mass spectrometry (GC/MS)-based metabolomics has been applied to study patients with primary hyperoxaluria types I and II, 2,8-dihydroxyadenine lithiasis, and xanthinuria types I to III. This study was performed to verify the usefulness of this technique for the diagnosis of PH3. Specifically, we evaluated an 8-month-old infant with recurrent kidney stones. <b>Methods:</b> GC/MS-based metabolomics was performed on spot urine samples using initial urease pretreatment without fractionation. <b>Results:</b> Metabolomics revealed increased levels of 2,4-dihydroxyglutarate and 4-hydroxyglutamate. No simultaneous elevations of these two critical biomarkers were observed in other patients, except for one case of PH3 confirmed by the identification of <i>HOGA1</i> mutations. A moderate increase in 4-hydroxyglutamate has been observed only in cases of primary hyperammonemia, in which analytes such as orotate, uridine, glutamine, or proline, but not 2,4-dihydroxyglutarate, are biomarkers, thus distinguishing PH3 from primary hyperammonemia. <b>Conclusions:</b> GC/MS-based urine metabolomics enables the rapid screening and chemical diagnosis of PH3 and other congenital anomalies that cause urolithiasis. This technique can also be used to monitor disease progression, as patients with PH3 benefit from long-term follow-up, particularly when transitioning from childhood to adulthood. The timely identification of patients with hereditary urolithiasis is crucial. To address this, a discussion was had about the current diagnostic criteria.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2026-04-18DOI: 10.3390/metabo16040276
Shichao Wang, Shu He, Congjun Yuan, Xingliang Chen, Hoang Van Sam, Wei Chen Lum, Yaquan Dou, Rui Shi
{"title":"Unveiling the Fragrant Secrets of <i>Dendrobium devonianum</i>: Terpenoid Pathways and Floral Scent Dynamics.","authors":"Shichao Wang, Shu He, Congjun Yuan, Xingliang Chen, Hoang Van Sam, Wei Chen Lum, Yaquan Dou, Rui Shi","doi":"10.3390/metabo16040276","DOIUrl":"https://doi.org/10.3390/metabo16040276","url":null,"abstract":"<p><strong>Background/objectives: </strong>The orchid <i>Dendrobium devonianum</i> Paxt., valued for its ornamental and medicinal properties, is widely used in horticulture, medicine, and food industries.</p><p><strong>Methods: </strong>This study investigated dynamic changes in aroma-active volatile organic compounds (VOCs) and associated gene expression in <i>D. devonianum</i> flowers across four developmental stages (bud, half bloom, full bloom, and aging) using headspace solid-phase microextraction, gas chromatography-mass spectrometry, and transcriptome analysis.</p><p><strong>Results: </strong>Floral VOCs, particularly volatile terpenoids and esters, were most abundant at full bloom. Among the 664 VOCs identified, α-hemelene, β-bisabolene, δ-naphthalene, perillyl alcohol, L-perillyl alcohol, terpinen-4-ol, 2-(4-methylphenyl)propan-2-ol, cis-3-hexenyl butyrate, and α-pinene were likely to contribute to floral scent. Terpene biosynthesis pathways played a pivotal role in floral fragrance formation. A comprehensive terpenoid biosynthesis pathway for <i>D. devonianum</i> floral scent was proposed, and eight genes encoding key regulatory enzymes were identified.</p><p><strong>Conclusions: </strong>These results provide new insights into terpenoid metabolism in Dendrobium and may guide future research on the utilization of floral scent.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}