Metabolism: clinical and experimental最新文献

{"title":"Metabolic regulation of tissue-resident immune cells: Molecular mechanisms and therapeutic implications","authors":"Zixiang Chen ,&nbsp;Fan Xiao ,&nbsp;Xiaoxia Zhu ,&nbsp;Wenhao Zhou ,&nbsp;Ke Rui ,&nbsp;Liwei Lu ,&nbsp;Jie Tian","doi":"10.1016/j.metabol.2025.156349","DOIUrl":"10.1016/j.metabol.2025.156349","url":null,"abstract":"<div><div>Many innate and adaptive immune cells are resident in non-lymphoid tissues and do not participate in peripheral circulation. These tissue-resident immune cells not only rapidly recognize and respond to local infections or injuries but also contribute to the maintenance of tissue homeostasis and immune balance. Immune cell function is closely associated with their metabolic state. Recent studies reveal that tissue-resident immune cells undergo unique metabolic reprogramming to adapt to their specific tissue microenvironment. This metabolic adaptation is crucial for their long-term survival, differentiation, and function. In this review, we systematically elaborate on the metabolic characteristics and tissue-specific regulatory mechanisms of CD8⁺ tissue-resident memory T cells (T_RM) and tissue-resident macrophages (TRMφs). Based on an in-depth analysis of the critical role of immunometabolic pathways in infection, cancer, and autoimmune diseases, we further summarize therapeutic strategies targeting these metabolic pathways and discuss their efficacy, potential side effects, and the challenges facing clinical translation.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156349"},"PeriodicalIF":10.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605330","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":"Corrigendum to “Exosomal miRNAs in muscle-bone crosstalk: Mechanistic links, exercise modulation and implications for sarcopenia, osteoporosis and osteosarcopenia” [metabolism. 2025 Jun 21:156333]","authors":"Bo Zhang,&nbsp;Yang Chen,&nbsp;Qiaojie Chen,&nbsp;Haijun Zhang","doi":"10.1016/j.metabol.2025.156351","DOIUrl":"10.1016/j.metabol.2025.156351","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156351"},"PeriodicalIF":10.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569805","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":"AEBP1 as a promising therapeutic target for skeletal muscle insulin resistance in type 2 diabetes mellitus: Convergent evidence from Mendelian randomization and functional validation","authors":"Chen Guo ,&nbsp;Jiani Li ,&nbsp;Xiaofei Yang ,&nbsp;Weinan Xie ,&nbsp;Fangxing Zeng ,&nbsp;Keyu Chen ,&nbsp;Wenjing Mi ,&nbsp;Cheng Tang ,&nbsp;Han Wang","doi":"10.1016/j.metabol.2025.156339","DOIUrl":"10.1016/j.metabol.2025.156339","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to skeletal muscle insulin resistance (IR). Currently, there is still a lack of relevant treatments. Summary-data-based Mendelian randomization (SMR) is a vital tool for identifying druggable targets in skeletal muscle to develop T2DM treatments.</div></div><div><h3>Methods</h3><div>Potential causative genetic factors in skeletal muscle and blood causally associated with T2DM were identified by SMR analysis. Bayesian colocalisation were used to validate causality. Pleiotropic impact of drug targets was assessed using phenome-wide MR (Phe-MR). Then, targeted overexpression or knockdown of AEBP1 in mouse myoblast cell lines (C2C12) and human skeletal muscle cells (HSkMCs) further validated the functional phenotype. Protein docking, co-IP and SPR were used to demonstrate protein-protein interactions.</div></div><div><h3>Results</h3><div>Both European and Asian populations revealed that AEBP1 was significantly associated with T2DM and its glycemic profile in blood and skeletal muscle, and was identified as a risk factor. Co-localisation analyses suggest that AEBP1 and T2DM originate from the same genetic variants. Meanwhile, targeted AEBP1 therapy has no potential adverse effects. Furthermore, AEBP1 was significantly expressed in <em>in vivo</em> and <em>in vitro</em> IR models and was consistent with the SMR results. Overexpression of AEBP1 further impaired insulin signalling and glucose transport mechanisms, exacerbating skeletal muscle IR. Targeting AEBP1 knockdown reversed these changes. Protein interaction experiments revealed that PI3K (p110β) is a direct target protein for AEBP1 to exert molecular functions.</div></div><div><h3>Conclusion</h3><div>Targeting AEBP1 therapy is expected to be a pivotal approach for the prevention and treatment of T2DM.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156339"},"PeriodicalIF":10.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575898","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 - author's reply.","authors":"Xinrong Zhang, Mindie H Nguyen","doi":"10.1016/j.metabol.2025.156350","DOIUrl":"10.1016/j.metabol.2025.156350","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156350"},"PeriodicalIF":10.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567541","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":"Reply to: Finerenone in the SGLT2i era: redundancy or complementarity?","authors":"John Hakim","doi":"10.1016/j.metabol.2025.156338","DOIUrl":"https://doi.org/10.1016/j.metabol.2025.156338","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156338"},"PeriodicalIF":10.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567542","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":"Response to \"expanding the clinical and Immunogenomic relevance of SAMD1 in hepatocellular carcinoma\".","authors":"Guo-Qiang Pan, Yu-Chuan Yan, Rui-Zhe Li, Zhao-Ru Dong, Tao Li","doi":"10.1016/j.metabol.2025.156336","DOIUrl":"10.1016/j.metabol.2025.156336","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156336"},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528911","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":"Finerenone in the SGLT2i era: Redundancy or complementarity?","authors":"Hongyi Chen, Yuying Ma, Qiang Wang","doi":"10.1016/j.metabol.2025.156337","DOIUrl":"10.1016/j.metabol.2025.156337","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156337"},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528910","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":"Best practice recommendations for the diagnosis and management of hypoparathyroidism","authors":"Aliya A. Khan ,&nbsp;Dalal S. Ali ,&nbsp;John P. Bilezikian ,&nbsp;Sigridur Björnsdottir ,&nbsp;Michael T. Collins ,&nbsp;Natalie E. Cusano ,&nbsp;Peter R. Ebeling ,&nbsp;Ghada El Haj Fuleihan ,&nbsp;Seiji Fukumoto ,&nbsp;Andrea Giustina ,&nbsp;Stephanie M. Kaiser ,&nbsp;Christian A. Koch ,&nbsp;Tayyab Khan ,&nbsp;Patty Keating ,&nbsp;Jian-Min Liu ,&nbsp;Christos S. Mantzoros ,&nbsp;Michael Mannstadt ,&nbsp;Ambrish Mithal ,&nbsp;Nancy D. Perrier ,&nbsp;Michele Rayes ,&nbsp;Maria Luisa Brandi","doi":"10.1016/j.metabol.2025.156335","DOIUrl":"10.1016/j.metabol.2025.156335","url":null,"abstract":"<div><h3>Background</h3><div>Hypoparathyroidism (HypoPT) is characterized by low serum calcium due to insufficient parathyroid hormone (PTH). This manuscript builds upon the 2022 international HypoPT guidelines and three systematic reviews, which have been further informed by updated narrative reviews and expert consensus. This paper presents current best practice consensus recommendations for the diagnosis and management of HypoPT.</div></div><div><h3>Methods</h3><div>An International Panel of Experts updated the previous systematic reviews (SR's), conducted narrative reviews, developed, and subsequently approved these best practice recommendations at the Parathyroid Summit, held as a pre-Endocrine Society meeting in May 2024 (Boston, USA).</div></div><div><h3>Results</h3><div>Diagnostic criteria for chronic HypoPT require hypocalcemia with inappropriately normal or low PTH levels. Conventional therapy is recommended as first line therapy and includes calcium supplementation, active vitamin D, correction of vitamin D inadequacy and correction of abnormalities in serum magnesium. Monitoring is required to achieve optimal serum calcium while avoiding hyperphosphatemia, hypercalciuria and declines in renal function. Assessment of HypoPT complications is required including skeletal health assessment in postmenopausal women and men over the age of 50 years. Specific strategies are provided for managing HypoPT during pregnancy and lactation as well as in children. PTH replacement with palopegteriparatide has been approved and is an important therapeutic option, especially when conventional therapy is inadequate or not tolerated.</div></div><div><h3>Conclusion</h3><div>These best practice recommendations provide a framework for HypoPT diagnosis and management, emphasizing individualized care, role of DNA analysis in the diagnosis of nonsurgical HypoPT, and role of PTH or PTH analogue therapy as appropriate. They complement the 2022 international guidelines and incorporate updated therapeutic recommendations from the past 3 years including the positioning of the newly approved molecule palopegteriparatide based on recent clinical trial data and expert consensus.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156335"},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528909","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":"Carboxylic acid metabolism in cancer: Mechanisms, microenvironment interactions, and therapeutic opportunities","authors":"Xiqing Bian ,&nbsp;Yue Zhuo ,&nbsp;Luo Zhou ,&nbsp;Yi Zhun Zhu ,&nbsp;Na Li ,&nbsp;Jian-Lin Wu","doi":"10.1016/j.metabol.2025.156334","DOIUrl":"10.1016/j.metabol.2025.156334","url":null,"abstract":"<div><div>Cancer cells reprogram their metabolism to favor aerobic glycolysis and enhance carboxylic acid metabolism, supporting their energy needs and promoting tumor progression. This review explores the role of carboxylic acids, such as lactate, fatty acids, and amino acids, in cancer through four key pathways: (1) lactate-mediated tumor microenvironment acidification and immune suppression, (2) fatty acid metabolism driving tumorigenesis, (3) amino acid regulation of cancer cell survival, and (4) the crosstalk between these metabolic networks. These pathways contribute to immune evasion, proliferation, and drug resistance by modulating key enzymes, transporters, and signaling mechanisms. Despite their therapeutic potential, targeting carboxylic acid metabolism remains challenging owing to tumor adaptability and metabolic heterogeneity. Future research directions include the development of isoform-specific inhibitors, combination therapies, and precision medicine approaches based on metabolic profiling. Understanding these interconnected pathways may reveal new vulnerabilities for innovative cancer treatments.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"171 ","pages":"Article 156334"},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518646","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":"Exosomal miRNAs in muscle-bone crosstalk: Mechanistic links, exercise modulation and implications for sarcopenia, osteoporosis and osteosarcopenia","authors":"Bo Zhang,&nbsp;Yang Chen,&nbsp;Qiaojie Chen,&nbsp;Haijun Zhang","doi":"10.1016/j.metabol.2025.156333","DOIUrl":"10.1016/j.metabol.2025.156333","url":null,"abstract":"<div><div>This review investigates the emerging role of exosomal microRNAs (miRNAs) as pivotal mediators of bidirectional communication between the skeletal muscle and bone tissue, with significant implications for age-related musculoskeletal disorders. In aging populations, sarcopenia often coexists with osteoporosis, forming osteosarcopenia, which markedly increases fracture risk, disability, and mortality. While traditional paradigms emphasize mechanical loading and endocrine pathways, emerging evidence has revealed that exosomes carrying bioactive miRNAs represent a novel class of paracrine factors in the muscle-bone axis. We examined how muscle-derived exosomal miRNAs (miR-34a and miR-27a-3p) influence bone metabolism, while bone-derived exosomal miRNAs (miR-486-5p) modulate muscle physiology. For each miRNA, we identified the target messenger RNAs (mRNAs) and signaling mechanisms. Importantly, exercise has emerged as a potent modulator of this crosstalk, altering exosomal miRNA profiles to promote anabolic outcomes in both tissues. This bidirectional communication contributes to osteosarcopenia pathophysiology, leading us to propose a novel “Exosomal miRNA Regulatory Network” for diagnosis and pathogenesis. Exosomal miRNAs show promise as early biomarkers for subclinical deterioration and therapeutic targets. However, methodological challenges in exosome isolation, incomplete characterization of miRNA networks, and aging complexity must be addressed before clinical implementation.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"170 ","pages":"Article 156333"},"PeriodicalIF":10.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366945","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}