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Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC. 代谢-免疫微环境串扰介导MASH-HCC的ICI抗性。
Trends in Endocrinology & Metabolism Pub Date : 2025-07-21 DOI: 10.1016/j.tem.2025.06.008
Yi Ju,Kequan Xu,Xi Chen,Tiangen Wu,Yufeng Yuan
{"title":"Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC.","authors":"Yi Ju,Kequan Xu,Xi Chen,Tiangen Wu,Yufeng Yuan","doi":"10.1016/j.tem.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.008","url":null,"abstract":"As a pivotal immunotherapy modality, immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in a variety of malignant tumors, including viral hepatocellular carcinoma (HCC). However, metabolic-associated steatohepatitis-related hepatocellular carcinoma (MASH-HCC) is significantly resistant to ICI, its metabolic-immune crosstalk mechanisms have not been systematically defined, and methods to improve the efficacy of ICI in this context are lacking. Thus, here we elucidate the microenvironmental features of MASH-HCC, focusing on tumor metabolic-immune crosstalk mechanisms such as metabolic reprogramming, metabolic stress, fibrosis, and the gut-liver axis, and summarize clinical and preclinical studies currently assessing whether metabolic drugs may help with overcoming ICI resistance and improving clinical efficacy against MASH-HCC.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"143 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684117","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}
引用次数: 0
A metabolic perspective on cuproptosis 从代谢角度看铜骨畸形
Trends in Endocrinology & Metabolism Pub Date : 2025-07-18 DOI: 10.1016/j.tem.2025.06.007
Yehua Li, Xiaodong Wang
{"title":"A metabolic perspective on cuproptosis","authors":"Yehua Li, Xiaodong Wang","doi":"10.1016/j.tem.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.007","url":null,"abstract":"Copper (Cu) is an essential trace element that plays a fundamental role in various biological processes, including electron transfer and enzymatic reactions. Cu homeostasis is tightly regulated by transporters, including CTR1 and ZnT1, that mediate Cu uptake, as well as by intracellular Cu chaperones and exporters such as ATP7A and ATP7B. Excessive accumulation of Cu can lead to cuproptosis, a form of regulated cell death characterized by Cu-induced lipoylated protein aggregation and degradation of Fe–S cluster proteins. We discuss how recent insights into Cu metabolism and cuproptosis have expanded our understanding of Cu homeostasis, and present new opportunities for the treatment of human diseases involving Cu imbalance, including Menkes and Wilson's diseases, neurodegenerative conditions, and cancer.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664773","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}
引用次数: 0
Industrialized diets modulate host eating behavior via the microbiome-gut-brain axis. 工业化饮食通过微生物群-肠-脑轴调节宿主的饮食行为。
Trends in Endocrinology & Metabolism Pub Date : 2025-07-17 DOI: 10.1016/j.tem.2025.06.002
Yi Jia Liow,Amar Sarkar,Rachel N Carmody
{"title":"Industrialized diets modulate host eating behavior via the microbiome-gut-brain axis.","authors":"Yi Jia Liow,Amar Sarkar,Rachel N Carmody","doi":"10.1016/j.tem.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.002","url":null,"abstract":"The gut microbiome is an important participant in the gut-brain axis and a key mediator of host-diet interactions that shape feeding behavior. These effects occur through microbial metabolism of dietary components - fiber, sugar, fat, and protein - into bioactive metabolites that influence microbiome-gut-brain signaling. Industrialized diets are enriched in highly processed, energy-dense foods characterized by elevated fat and sugar content and reduced fiber content. These diets have been implicated in altered eating behaviors involving the microbiome-gut-brain axis. We propose that different ratios of dietary substrates in industrialized diets perturb the microbiome-gut-brain axis, thereby driving changes in microbial metabolite production and downstream signaling with behavioral consequences. Integration of microbiome and neuroscience methodologies will help to delineate the causal mechanisms by which diet shapes interoceptive signaling and eating behavior.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664262","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}
引用次数: 0
Unraveling the sweet connection between pancreatic cancer and hyperglycemia. 揭示胰腺癌和高血糖之间的甜蜜联系。
Trends in Endocrinology & Metabolism Pub Date : 2025-07-01 DOI: 10.1016/j.tem.2025.06.003
Zoë Post,Dauris Rosario Lora,Wojciech Blogowski
{"title":"Unraveling the sweet connection between pancreatic cancer and hyperglycemia.","authors":"Zoë Post,Dauris Rosario Lora,Wojciech Blogowski","doi":"10.1016/j.tem.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.003","url":null,"abstract":"Pancreatic adenocarcinoma (PaC) is one of the deadliest cancers, primarily due to late-stage diagnosis and limited treatment options. A bidirectional relationship exists between PaC and diabetes mellitus (DM), where glucose abnormalities both cause and result from PaC. In this review, we examine the complex pathophysiology of PaC-induced hyperglycemia, focusing on impaired insulin sensitivity, β cell dysfunction, chronic inflammation, and alterations in the gut microbiome and circadian rhythm. We discuss how PaC induces insulin resistance through disrupted signaling and proinflammatory factors, as well as β cell dysfunction through oxidative stress and adrenomedullin-mediated insulin secretion inhibition. In addition, emerging research highlights the role of the gut microbiome in PaC and hyperglycemia. Comprehensive understanding of these mechanisms is critical for early detection and improved treatment strategies for PaC.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547824","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}
引用次数: 0
Early nutritional interventions for chronic low-grade inflammation 慢性低度炎症的早期营养干预
Trends in Endocrinology & Metabolism Pub Date : 2025-06-27 DOI: 10.1016/j.tem.2025.06.001
Zhangtie Wang, Changzheng Yuan, Tao Huang, Baiyi Lu
{"title":"Early nutritional interventions for chronic low-grade inflammation","authors":"Zhangtie Wang, Changzheng Yuan, Tao Huang, Baiyi Lu","doi":"10.1016/j.tem.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.001","url":null,"abstract":"Current research on inflammatory disorders tends to focus on the advanced stages of disease; however, acting against chronic low-grade inflammation (a stage before overt disease) through early nutritional interventions may be an alternative, beneficial approach. We systematically evaluate how diet modulates chronic low-grade inflammation through several physiological processes. Furthermore, we suggest three intervention strategies tailored to specific stages of disease: (i) promoting anti-inflammatory dietary patterns in the general population, (ii) implementing precision nutrition targeting inflammatory biomarkers in individuals at risk, and (iii) utilizing adjuvant dietary therapies for existing inflammation. Overall, we argue that early nutritional interventions could address the unmet clinical need to alter inflammatory trajectories before clinical manifestation.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516050","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}
引用次数: 0
Branched metabolic pathways to generate heme and heat. 分支代谢途径产生血红素和热量。
Trends in Endocrinology & Metabolism Pub Date : 2025-06-24 DOI: 10.1016/j.tem.2025.06.005
Takeshi Yoneshiro,Makoto Arai,Juro Sakai
{"title":"Branched metabolic pathways to generate heme and heat.","authors":"Takeshi Yoneshiro,Makoto Arai,Juro Sakai","doi":"10.1016/j.tem.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.tem.2025.06.005","url":null,"abstract":"Heme has remarkable functions in mitochondrial energetics. Recently, Duerre et al. found that branched-chain amino acids (BCAA) are preferentially utilized for heme biosynthesis to facilitate mitochondrial thermogenesis in brown fat. Disrupting heme biosynthesis shifts the metabolic fate of BCAAs toward histone propionylation, inhibiting the transcription of thermogenic genes.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487908","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}
引用次数: 0
MAP kinase phosphatases in metabolic diseases. 代谢性疾病中的MAP激酶磷酸酶。
Trends in Endocrinology & Metabolism Pub Date : 2025-06-23 DOI: 10.1016/j.tem.2025.05.002
Ananya Hota,Anton M Bennett
{"title":"MAP kinase phosphatases in metabolic diseases.","authors":"Ananya Hota,Anton M Bennett","doi":"10.1016/j.tem.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.tem.2025.05.002","url":null,"abstract":"Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are essential regulators of MAPK signaling pathways. MKPs perform critical roles in various cellular responses by dephosphorylating the regulatory residues and thereby inactivating MAPKs. Many studies have highlighted the role of MKPs in metabolic diseases, including obesity, diabetes, and cardiovascular disorders. These metabolic diseases disrupt key pathways such as insulin signaling, glucose homeostasis, lipid metabolism, and other inflammatory processes. Here, we provide a comprehensive overview of the current understanding of the role played by MKPs in metabolism and highlight their roles in metabolic diseases and potential as therapeutic targets.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478673","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}
引用次数: 0
Expanding the understanding of insulin resistance in brain and periphery. 扩大对脑及外周胰岛素抵抗的认识。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-19 DOI: 10.1016/j.tem.2025.04.010
Wenqiang Chen,Stephanie Kullmann,Elizabeth M Rhea
{"title":"Expanding the understanding of insulin resistance in brain and periphery.","authors":"Wenqiang Chen,Stephanie Kullmann,Elizabeth M Rhea","doi":"10.1016/j.tem.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.010","url":null,"abstract":"Insulin resistance is a central feature of metabolic disorders such as type 2 diabetes (T2D). While studies on this disorder have largely been linked to glucose metabolism and intracellular signaling, recent advances reveal that insulin resistance extends beyond traditional glucose regulatory pathways, impacting multiple organs including the brain, contributing to cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD). This opinion revisits insulin resistance through molecular, cellular, and systemic perspectives, emphasizing the intersection between peripheral and brain insulin resistance (BIR), the role of the blood-brain barrier (BBB), and emerging biomarkers. Furthermore, we integrate insights from multi-omics and neuroimaging studies to refine our understanding, advocating for a broader perspective that informs early detection and intervention in metabolic and neurodegenerative diseases.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103811","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}
引用次数: 0
B vitamins as adjunct therapies for depressive disorder. B族维生素作为抑郁症的辅助疗法。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-14 DOI: 10.1016/j.tem.2025.04.007
Zi-Qing Zheng,Liang Shen,Li-Ming Zhao,Hong-Fang Ji
{"title":"B vitamins as adjunct therapies for depressive disorder.","authors":"Zi-Qing Zheng,Liang Shen,Li-Ming Zhao,Hong-Fang Ji","doi":"10.1016/j.tem.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.007","url":null,"abstract":"The rising prevalence of depressive disorder worldwide requires better interventional avenues. B vitamins are gaining increasing interest as potential therapeutic approaches in this context given current evidence for a bidirectional association between B vitamin deficiency and depressive disorder. We discuss how B vitamins and B vitamin-associated probiotic supplementation may represent an effective adjunctive treatment for depression, and highlight the key metabolic mechanisms involved. We also provide a perspective on the future of this field and advocate for further high-quality clinical trials to assess the benefits of B vitamins in this context and optimize their clinical implementation.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065582","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}
引用次数: 0
Metabolomics-enabled biomarker discovery in breast cancer research. 代谢组学在乳腺癌研究中的应用。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-13 DOI: 10.1016/j.tem.2025.04.008
Julia Füreder,Eva S Schernhammer,A Heather Eliassen,Sabina Sieri,Benedikt Warth
{"title":"Metabolomics-enabled biomarker discovery in breast cancer research.","authors":"Julia Füreder,Eva S Schernhammer,A Heather Eliassen,Sabina Sieri,Benedikt Warth","doi":"10.1016/j.tem.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.008","url":null,"abstract":"Breast cancer (BC) remains the most prevalent malignancy among women worldwide. While genetic predisposition and reproductive history are key contributors to its development, modifiable risk factors are also important, particularly those linked to lifestyle behaviors, often influencing the endogenous metabolome. Over the past decade, mass spectrometry-based metabolomics has enabled agnostic investigations into correlations between the metabolome and BC risk. Here we review recent results from prospective nested case-control studies, which have led to the identification of significantly different metabolites between women who subsequently developed BC and those who did not. As replication of these findings remains limited, we emphasize the need for robust quantitative validation studies, cancer subtype-specific analyses in diverse populations, and expanded chemical space coverage of analytical assays.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982457","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}
引用次数: 0
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