Metabolism open最新文献

{"title":"Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease","authors":"Wei Meng , Junli Liu , Xun Huang","doi":"10.1016/j.metop.2025.100390","DOIUrl":"10.1016/j.metop.2025.100390","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100390"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deoxycholic Acid and Lipoteichoic Acid cooperatively drive macrophage M2/M1 polarization via TGR5/STAT3 and TLR2/NF-κB to fuel HCC progression in obesity","authors":"Jian Wu ,&nbsp;wen Zheng ,&nbsp;Xu-zhen Ding ,&nbsp;Qiao-ping Jin ,&nbsp;Ming-xing Ding","doi":"10.1016/j.metop.2025.100420","DOIUrl":"10.1016/j.metop.2025.100420","url":null,"abstract":"<div><h3>Background</h3><div>Obesity-related hepatocellular carcinoma (HCC) is associated with gut microbiota dysbiosis. However, the specific roles of key microbial metabolites, deoxycholic acid (DCA) and lipoteichoic acid (LTA), in modulating the immune microenvironment and promoting HCC progression are not fully understood.</div></div><div><h3>Aim</h3><div>This study aimed to elucidate the synergistic effects and mechanisms of DCA and LTA in obesity-related HCC.</div></div><div><h3>Methods</h3><div>An obesity-related HCC model was established in mice using a high-fat diet combined with diethylnitrosamine. In vitro, macrophage and HCC cell co-culture systems were utilized, along with gene knockdown approaches.</div></div><div><h3>Results</h3><div>Combined DCA and LTA treatment synergistically exacerbated liver fibrosis and tumorigenesis in the mouse model. This was accompanied by suppressed expression of Cdkn1a and Cdkn2a, and activation of GPC-3 and CD44. Mechanistically, DCA promoted M2 macrophage polarization via the TGR5-STAT3 axis, whereas LTA drove M1 polarization via TLR2-NF-κB. In co-culture, knockdown of TLR2 and TGR5 reversed the pro-tumorigenic effects of DCA and LTA, inhibiting the epithelial-mesenchymal transition and reducing cancer cell invasion.</div></div><div><h3>Conclusion</h3><div>DCA and LTA synergistically promote HCC progression in obesity by co-modulating the TLR2-TGR5 signaling axis in macrophages, thereby reshaping the tumor immune microenvironment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100420"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Prevalence of normal weight obesity among adults in Southeast Asia: Insights from a systematic review and meta-analysis” [Metabol. Open 28C (2025) 100416]","authors":"K.G. Sruthi ,&nbsp;C. Aditya ,&nbsp;Paramjot Panda ,&nbsp;Jyoti Ranjan Mohanty ,&nbsp;Manas Ranjan Behera","doi":"10.1016/j.metop.2025.100425","DOIUrl":"10.1016/j.metop.2025.100425","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100425"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational diabetes alters prefrontal neurochemistry and disrupts maternal behaviors: Role of Fibrillin-1, serotonin, and TNF-α in rats","authors":"Samira Khayat ,&nbsp;Hamed Fanaei ,&nbsp;Abdolvahed Safarzaei","doi":"10.1016/j.metop.2025.100422","DOIUrl":"10.1016/j.metop.2025.100422","url":null,"abstract":"<div><h3>Objective</h3><div>Gestational diabetes mellitus (GDM) is a metabolic disorder that can impact various aspects of maternal behavior and neurochemical processes. This study aimed to investigate the effects of GDM on FBN1 (fibrillin-1) gene expression, TNF-alpha, serotonin and maternal behavior in rat.</div></div><div><h3>Materials and methods</h3><div>A total of twenty female Wistar rats were randomly divided into two groups: the control group and the gestational diabetes mellitus (GDM) group. The study compared maternal behavior patterns between the GDM and control groups and measured the following in the hippocampus and prefrontal cortex: TNF-α and serotonin levels (via ELISA), and FBN1 mRNA expression (via qRT-PCR).</div></div><div><h3>Results</h3><div>The findings demonstrated that TNF-α levels (<em>P</em> = 0.0025) were significantly higher in the prefrontal cortex of the GDM group compared to the control group, whereas serotonin levels (<em>P</em> = 0.0037) were significantly lower. Additionally, <em>FBN1</em> mRNA expression levels (<em>P</em> = 0.012) in the prefrontal cortex of GDM group were significantly higher than those in the control group. In terms of maternal behavior, the GDM group exhibited weakened behaviors compared to the control group. Specifically, endurance of maternal behaviors such as the duration of breastfeeding (P = 0.024), nesting (P = 0.016), and pup grooming (P = 0.017) were significantly decreased in the GDM group compared to control group. The speed of integration of maternal behaviors, specifically the latency to onset of pup retrieval (P = 0.0018), significantly increased, while the number of breastfeeding instances (P = 0.0026) significantly decreased in the GDM group compared to the control group. Furthermore, the emotionality (self-calming) aspect of maternal behavior, specifically self-grooming, exhibited a significant decreases in both duration (P = 0.0097) and number of instances (P = 0.0029) in the GDM group compared to the control group. In the hippocampus, only TNF-α levels were significantly elevated in the GDM group (P = 0.0003); no significant differences were found in serotonin or FBN1 mRNA expression.</div></div><div><h3>Conclusion</h3><div>These results demonstrate that GDM significantly dysregulates prefrontal cortex neurochemistry (increasing TNF-α and FBN1 mRNA while decreasing serotonin) and profoundly weakens maternal behavior, affecting its endurance, speed of integration, and emotional components in rats.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100422"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lysosomal surveillance response promotes healthspan in C. elegans","authors":"Liaoyuan Zheng ,&nbsp;Junli Liu","doi":"10.1016/j.metop.2025.100396","DOIUrl":"10.1016/j.metop.2025.100396","url":null,"abstract":"<div><div>Lysosomes, the cellular recycling hubs, are indispensable for maintaining homeostasis by degrading misfolded proteins, damaged organelles, and foreign pathogens. Their dysfunction is a hallmark of aging and age-related neurodegenerative diseases, where impaired clearance of toxic protein aggregates drives pathogenesis. Nevertheless, the mechanisms by which lysosomal function can be enhanced to mitigate these detrimental processes remain inadequately understood. A recent study conducted by Li et al. describes a newly identified transcriptional program, the Lysosomal Surveillance Response (LySR), that, when activated, significantly extends healthspan and reduces proteotoxicity in <em>C. elegans</em>. This adaptive transcriptional program, governed by the GATA transcription factor, ELT-2, and modulated by the acetyltransferase CBP-1, operates independently of canonical longevity pathways such as the DAF-2 insulin-like signaling. This work not only unveils a previously unrecognized longevity pathway but also charts a new course for developing therapies targeting aging and neurodegeneration.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100396"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Close multilevel links between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus","authors":"A.G. Holleboom ,&nbsp;S.M. Francque ,&nbsp;K. Cusi ,&nbsp;C. Caussy","doi":"10.1016/j.metop.2025.100424","DOIUrl":"10.1016/j.metop.2025.100424","url":null,"abstract":"<div><div>Since liver cirrhosis due to Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) was first described in patients with diabetes mellitus, the prevalence and severity of this liver disease have increased dramatically, driven by the increase in obesity and type 2 diabetes mellitus (T2DM). Strong epidemiological links between MASLD, insulin resistance and T2DM exist: T2DM is associated with higher prevalence and severity of MASLD, up to hepatic decompensation and hepatocellular carcinoma, and MASLD is in turn associated with incident T2DM Mechanistic studies support insulin resistance of metabolic tissues as the root cause of MASLD, whereas hepatic insulin resistance in turn contributes to hyperglycemia. Several pharmacological agents including incretin-based strategies, FGF21 analogues and the panPPAR agonist lanifibranor target the interface of MASLD and T2DM and have thereby shown promise to improve MASH and associated liver fibrosis. In light of the evident close multilevel links between MASLD and T2DM, care development efforts for MASLD in guidelines, local protocols and implementation strategies should aim to involve hepatologists, diabetologists, PCPs and their affiliated care teams in a joint effort to address the growing burden of fibrotic MASLD.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100424"},"PeriodicalIF":2.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between triglyceride glucose-body mass index and MASH, cardiovascular disease in MASLD patients: a cross-sectional study and machine learning analysis","authors":"Xiaoxuan Tang ,&nbsp;Fenglan Wang ,&nbsp;Yiran Liu ,&nbsp;Yujia Gao ,&nbsp;Mengxi Li ,&nbsp;Chong Liu ,&nbsp;Duanming Zhuang ,&nbsp;Bin Zhang","doi":"10.1016/j.metop.2025.100423","DOIUrl":"10.1016/j.metop.2025.100423","url":null,"abstract":"<div><h3>Background</h3><div>The triglyceride glucose-body mass index (TyG-BMI) is a useful marker for metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). However, its ability to differentiate metabolic dysfunction-associated steatohepatitis (MASH) and CVD risk among patients with MASLD requires further investigation. This study evaluates the association between TyG-BMI and MASH/CVD risk in patients with MASLD and applies machine learning (ML) to identify relevant risk factors.</div></div><div><h3>Methods</h3><div>The study used data from National Health and Nutrition Examination Survey (NHANES) to analyzed associations between TyG-BMI and two clinical outcomes: MASH, defined by the FibroScan-AST (FAST) score ≥0.35, and self-reported CVD. Participants were categorized based on TyG-BMI quartiles: Q1 (&lt;246.79), Q2 (246.79–280.32), Q3 (280.33–323.99), and Q4 (≥324.00). Multivariate survey-weighted logistic regression and restricted cubic splines (RCS) were used to assess relationships and potential nonlinearity. Multiple ML models were employed, with feature importance interpreted via Shapley Additive Explanations (SHAP) analysis.</div></div><div><h3>Results</h3><div>Among 674 MASLD participants (390 males), higher TyG-BMI was independently associated with increased risks of MASH and CVD risk. Compared with Q1, Q4 had adjusted odds ratios of 24.46 (95 % CI: 2.94–203.31, P = 0.003) for MASH and 3.53 (95 % CI: 1.26–9.90, P = 0.017) for CVD. RCS indicated linear relationships between TyG-BMI and both outcomes. The gradient boosting machine and support vector machine exhibited the optimal performance best in discriminating high-risk MASH (ROC: 0.910) and CVD (ROC: 0.773), confirming TyG-BMI as a significant risk factors.</div></div><div><h3>Conclusion</h3><div>TyG-BMI effectively identifies MASH and CVD risk in patients with MASLD, offering clinicians a practical tool for risk stratification and management.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100423"},"PeriodicalIF":2.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel causal associations between plasma metabolites and prostate cancer risk revealed by mendelian randomization","authors":"Hanghang Chen ,&nbsp;Huiduo Zhao ,&nbsp;Bingxin Meng ,&nbsp;Qi Liu","doi":"10.1016/j.metop.2025.100421","DOIUrl":"10.1016/j.metop.2025.100421","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is a major global health concern for men, yet its underlying metabolic mechanisms are not fully understood. Identifying causal metabolites could reveal novel pathways for risk assessment and prevention.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive two-sample Mendelian randomization (TSMR) study following STROBE-MR guidelines. Genetic instruments for plasma metabolites were derived from two independent sources, including the METSIM study, a cohort exclusively comprising Finnish men, and the Canadian Longitudinal Study on Aging (CLSA). Summary-level data for PCa were obtained from the PRACTICAL consortium and FinnGen. Inverse variance weighted (IVW) was the primary analysis method, supplemented by sensitivity analyses and Bayesian colocalization (coloc) to assess shared causal genetic variants, a key methodological strength enhancing causal inference.</div></div><div><h3>Results</h3><div>Our analysis identified four plasma metabolites with a significant causal relationship with PCa risk. Ribitol was associated with a reduced risk, while N2,N5-diacetylornithine, N-acetylarginine, and N-acetylcitrulline were associated with an elevated risk. These findings were consistent across datasets and robust in sensitivity analyses. Colocalization analysis provided strong evidence (PP.H4 &gt; 0.8) for a shared causal variant at the rs10201159 locus between N2,N5-diacetylornithine and PCa.</div></div><div><h3>Conclusion</h3><div>This study provides robust genetic evidence supporting a causal role of specific plasma metabolites in prostate cancer development. The incorporation of a male-exclusive metabolomic dataset (METSIM) strengthens the validity of our findings for this male-specific cancer. These metabolites represent promising candidates for further mechanistic investigation into prostate cancer etiology and potential translation into clinical biomarkers.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100421"},"PeriodicalIF":2.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery","authors":"Zhongpeng Qiu ,&nbsp;Dejing Shang","doi":"10.1016/j.metop.2025.100418","DOIUrl":"10.1016/j.metop.2025.100418","url":null,"abstract":"<div><div>The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with chronic inflammation within the islet microenvironment, where pancreatic islet macrophages serve as central orchestrators of local immune regulation. This review provides a systematic overview of the ontogeny, phenotypic heterogeneity, and functional roles of pancreatic islet macrophages in T2DM pathology. Pancreatic islet macrophages contribute to β-cell proliferation and the maintenance of islet homeostasis through the secretion of various growth factors, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Under conditions of metabolic stress, including lipotoxicity and glucotoxicity, these macrophages are polarized toward a pro-inflammatory phenotype. In this state, they impair β-cell function by releasing inflammatory mediators, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Furthermore, this article discusses potential clinical strategies that target pancreatic islet macrophages—such as anti-inflammatory agents and immunomodulators—highlighting their promise as novel perspectives for precise intervention in T2DM.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100418"},"PeriodicalIF":2.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotics, prebiotics, synbiotics, and FMT for glycemic control: A systematic review of clinical efficacy and mechanistic readouts in type 2 diabetes and related dysglycemia","authors":"Neda Shalbaf ,&nbsp;Soheila Sadeghi ,&nbsp;Sina Homaee ,&nbsp;Farnaz Saberian","doi":"10.1016/j.metop.2025.100419","DOIUrl":"10.1016/j.metop.2025.100419","url":null,"abstract":"<div><h3>Objective</h3><div>To systematically evaluate the clinical efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on glycemic control in adults with type 2 diabetes (T2D) and related dysglycemia, and to synthesize associated mechanistic changes in microbial metabolites and composition.</div></div><div><h3>Methods</h3><div>A systematic review was conducted following PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 2025 for randomized controlled trials (RCTs) in adults with T2D, prediabetes, or metabolic syndrome. Interventions included probiotics, prebiotics, synbiotics, or FMT compared to control. Outcomes were glycemic indices (e.g., HbA1c, HOMA-IR) and mechanistic biomarkers (e.g., SCFAs, bile acids). Risk of bias was assessed using the Cochrane RoB 2 tool. A narrative synthesis was performed.</div></div><div><h3>Results</h3><div>Thirty studies were included. Multi-strain probiotics, prebiotics, and synbiotics yielded modest but significant improvements in HbA1c (≈−0.2 to −0.4 %), fasting glucose, and HOMA-IR, particularly with durations ≥12 weeks. These benefits were linked to mechanistic shifts, including increased circulating butyrate and ursodeoxycholate, enrichment of SCFA-producing taxa, and reduced endotoxemia. Efficacy was moderated by concomitant medications: metformin use was synergistic, while sulfonylureas attenuated effects. FMT consistently improved clamp-measured insulin sensitivity in insulin-resistant phenotypes, but its effects on HbA1c were less consistent and donor-dependent.</div></div><div><h3>Conclusion</h3><div>Microbiome-targeted interventions, especially multi-strain probiotics and substrate-matched synbiotics, are effective adjuncts for improving glycemic control, with effects mediated through microbial metabolite production. FMT primarily modulates insulin sensitivity. Clinical outcomes are context-dependent, influenced by intervention design, duration, and pharmacomicrobiomic interactions.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100419"},"PeriodicalIF":2.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}