Metabolism: clinical and experimental最新文献

{"title":"Sedentary behaviour and cardiometabolic health: Integrating the potential underlying molecular health aspects","authors":"Wouter M.A. Franssen ,&nbsp;Ine Nieste ,&nbsp;Kenneth Verboven ,&nbsp;Bert O. Eijnde","doi":"10.1016/j.metabol.2025.156320","DOIUrl":"10.1016/j.metabol.2025.156320","url":null,"abstract":"<div><div>During the last decades, sedentary behaviour has been recognised as an interdependent risk factor for cardiometabolic health and premature mortality. Prolonged sedentary behaviour is associated with increased risks for chronic non-communicable diseases (NCDs) such as obesity, chronic respiratory diseases, type 2 diabetes mellitus, cardiovascular diseases and cancer due to disturbances in cardiometabolic health. However, despite the increased evidence supporting these associations, the underlying molecular mechanisms to the development of these NCDs remain largely unknown. In this review, we therefore discuss the existing evidence with regard to the potential underlying molecular mechanisms of sedentary behaviour-induced perturbations in cardiometabolic health. Here, various potential mechanisms related to carbohydrate metabolism, lipid metabolism, oxidative stress, inflammation and micro- and macro vascular function will be outlined. In addition, we summarise the current evidence on various strategies to interrupt sedentary behaviour and their effects on cardiometabolic health outcomes, including insulin sensitivity, blood lipid profiles, and cardiovascular health. Finally, we highlight key research gaps in the field of sedentary behaviour in relation to the underlying molecular mechanisms.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"170 ","pages":"Article 156320"},"PeriodicalIF":10.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderic acid T, a novel activator of pyruvate carboxylase, exhibits potent anti-liver cancer activity","authors":"Bo Lei ,&nbsp;Mengjie Zhang ,&nbsp;Xiangrui Shi ,&nbsp;Na Feng ,&nbsp;Jun Yin ,&nbsp;Rui Dong ,&nbsp;Chuanming Xie ,&nbsp;Yinan Zhu ,&nbsp;Jian-Jiang Zhong ,&nbsp;Bing Ni","doi":"10.1016/j.metabol.2025.156321","DOIUrl":"10.1016/j.metabol.2025.156321","url":null,"abstract":"<div><h3>Background</h3><div>Ganoderic acid T (GAT), a lanostane triterpenoid isolated from the methanol extract of <em>G. lucidum</em> mycelia, has demonstrated potent antitumor activity against various human cancer types. However, the specific molecular targets of GAT in cancer cells remain largely unknown. Therefore, this study systematically investigates these targets using the <em>in vitro</em> and <em>in vivo</em> hepatocellular carcinoma (HCC) model.</div></div><div><h3>Methods</h3><div>The anti-tumor activities of GAT were validated in HCC cells, xenograft tumor models in nude mice, and patient-derived organoid models. The specific molecular target of GAT was identified through targeted fishing techniques. Experimental approaches such as proteomics, metabolomics, biotin pull-down assays, molecular docking studies, molecular dynamics simulations, DARTS, CETSA, and biolayer interferometry (BLI) were employed to confirm the binding between GAT and its molecular target as well as elucidate the underlying mechanism.</div></div><div><h3>Results</h3><div>We have identified pyruvate carboxylase (PC) as a direct target of GAT. GAT, through its binding to the pocket composed of Arg453, Thr457, and Ile459 of PC, enhances the activity of PC, consequently disrupting the anaplerotic flux mediated by PC into the tricarboxylic acid (TCA) cycle. This disruption leads to impaired mitochondrial oxidative phosphorylation (OXPHOS) via the induction of reactive oxygen species (ROS)-mediated JNK/p38 MAPK signaling pathways, ultimately inhibiting HCC cell proliferation. Furthermore, molecular dynamics simulation suggests that GAT binds to and interacts with the biotin carboxylase (BC) domain of PC. This interaction potentially induces conformational changes in the protein structure of PC, leading to a tighter arrangement within the BC domain and stabilizing formation of a catalytically competent tetramer configuration for PC. The mutation of these key sites resulted in the destabilization of the BC domain and a reduction in the cytotoxic effect of GAT on HCC cells.</div></div><div><h3>Conclusion</h3><div>Overall, these findings demonstrate that GAT directly targets PC through an allosteric mechanism, providing valuable insights into the anti-HCC properties of GAT.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"170 ","pages":"Article 156321"},"PeriodicalIF":10.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144229907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASLD may influence female-specific cancer risk indirectly through shared metabolic pathways rather than direct causation","authors":"Wenjie Li ,&nbsp;Ruxue Lv","doi":"10.1016/j.metabol.2025.156322","DOIUrl":"10.1016/j.metabol.2025.156322","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156322"},"PeriodicalIF":11.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of Established and Novel Non-invasive Tests, Including New Clinical and Metabolomics-Based Machine Learning Models, for Detecting MASH with Fibrosis Stages F2-F3: A First-in-Class Approach in the post-Resmetirom approval era","authors":"Konstantinos Stefanakis ,&nbsp;Geltrude Mingrone ,&nbsp;Jacob George ,&nbsp;Christos S. Mantzoros","doi":"10.1016/j.metabol.2025.156206","DOIUrl":"10.1016/j.metabol.2025.156206","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156206"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited Stress Vulnerability Exacerbates Obesity-induced Metabolic Alterations Through Dysfunctional Adipose Tissue","authors":"Saumya Kishor Mehta,&nbsp;Michaella Ben-Shachar,&nbsp;Albert Pinhasov,&nbsp;Tovit Rosenzweig","doi":"10.1016/j.metabol.2025.156207","DOIUrl":"10.1016/j.metabol.2025.156207","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156207"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of Insulin Resistance, Type 2 Diabetes Mellitus, Obesity, and Colorectal Cancer Occurrence","authors":"Chong-Chi Chiu ,&nbsp;Chao-Ming Hung","doi":"10.1016/j.metabol.2025.156198","DOIUrl":"10.1016/j.metabol.2025.156198","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156198"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Biomarkers of Metabolic Inflammation: The Predictive Accuracy of Plasma Water T2 Exceeds That of High-Sensitivity C-Reactive Protein and Erythrocyte Sedimentation Rate","authors":"David P. Cistola ,&nbsp;Alok K. Dwivedi","doi":"10.1016/j.metabol.2025.156210","DOIUrl":"10.1016/j.metabol.2025.156210","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156210"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Targeting Inflammasome Signaling: Ginsana-115 as Prime Driver in Insulin Resistance/ cardiovascular Risk (CVD) in Prototypal Brain Disorder: Schizophrenia","authors":"Autumn Carriere,&nbsp;Simon S. Chiu,&nbsp;Michel Woodbury,&nbsp;Mariwan Husni,&nbsp;John Copen,&nbsp;Allison Foskett,&nbsp;Ed Lui,&nbsp;Robbie Campbell","doi":"10.1016/j.metabol.2025.156216","DOIUrl":"10.1016/j.metabol.2025.156216","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156216"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3, Multicenter, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Avexitide in Post-Bariatric Hypoglycemia (LUCIDITY)","authors":"Ryan Miller ,&nbsp;Marilyn Tan ,&nbsp;Tracey McLaughlin ,&nbsp;Mary Elizabeth Patti ,&nbsp;Suzanne Bijl ,&nbsp;Jennifer Hardy ,&nbsp;Jorgji Kerthi ,&nbsp;Jamie Timmons ,&nbsp;Yuehui Wu ,&nbsp;Zhengyu Yang ,&nbsp;Lahar Mehta ,&nbsp;Colleen Craig","doi":"10.1016/j.metabol.2025.156220","DOIUrl":"10.1016/j.metabol.2025.156220","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156220"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Hypercortisolism in Patients with Difficult-to-Control Type 2 Diabetes and High Blood Pressure: Results from CATALYST","authors":"Yehuda Handelsman ,&nbsp;Vanita R. Aroda ,&nbsp;Timothy Bailey ,&nbsp;Robert S. Busch ,&nbsp;John B. Buse ,&nbsp;Elena Christofides ,&nbsp;Ralph A. DeFronzo ,&nbsp;Bradley Eilerman ,&nbsp;Vivian Fonseca ,&nbsp;Adline Ghazi ,&nbsp;Steven E. Kahn ,&nbsp;Mark Kipnes ,&nbsp;Dan Lender ,&nbsp;Jonathan G. Ownby ,&nbsp;Jean Park ,&nbsp;Julio Rosenstock ,&nbsp;Michael Shanik ,&nbsp;Lance Sloan ,&nbsp;Ron Swerdloff ,&nbsp;Guillermo Umpierrez ,&nbsp;Daniel Einhorn","doi":"10.1016/j.metabol.2025.156214","DOIUrl":"10.1016/j.metabol.2025.156214","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"168 ","pages":"Article 156214"},"PeriodicalIF":10.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}