Pub Date : 2025-07-01DOI: 10.1016/j.tem.2025.06.003
Zoë Post,Dauris Rosario Lora,Wojciech Blogowski
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.
{"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}
Pub Date : 2025-06-27DOI: 10.1016/j.tem.2025.06.001
Zhangtie Wang, Changzheng Yuan, Tao Huang, Baiyi Lu
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.
{"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}
Pub Date : 2025-06-24DOI: 10.1016/j.tem.2025.06.005
Takeshi Yoneshiro,Makoto Arai,Juro Sakai
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.
{"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}
Pub Date : 2025-06-23DOI: 10.1016/j.tem.2025.05.002
Ananya Hota,Anton M Bennett
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.
{"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}
Pub Date : 2025-05-19DOI: 10.1016/j.tem.2025.04.010
Wenqiang Chen,Stephanie Kullmann,Elizabeth M Rhea
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.
{"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}
Pub Date : 2025-05-14DOI: 10.1016/j.tem.2025.04.007
Zi-Qing Zheng,Liang Shen,Li-Ming Zhao,Hong-Fang Ji
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.
{"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}
Pub Date : 2025-05-13DOI: 10.1016/j.tem.2025.04.008
Julia Füreder,Eva S Schernhammer,A Heather Eliassen,Sabina Sieri,Benedikt Warth
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.
{"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}
Pub Date : 2025-05-08DOI: 10.1016/j.tem.2025.04.002
Julianna G Supplee,Ronen Marmorstein,Kathryn E Wellen
Disorders of lipid metabolism, including hyperlipidemia, atherosclerosis, and metabolic dysfunction-associated steatotic liver disease, are increasing across the globe. Bempedoic acid (BPA) is a first-in-class drug for the treatment of hypercholesterolemia and cardiac risk reduction, which may particularly benefit those who do not tolerate statins. Inhibition of hepatic ATP-citrate lyase (ACLY) is widely accepted as the main mediator of its observed clinical effects. However, BPA treatment also has ACLY-independent effects on lipid metabolism, as the structural similarity of BPA to endogenous fatty acids allows it to trigger multiple lipid-signaling pathways. Here, we review the molecular targets of BPA and related 'decoy fatty acid' drugs and identify areas where further study is warranted as these molecules are evaluated for clinical indications.
{"title":"Molecular targets of bempedoic acid and related decoy fatty acids.","authors":"Julianna G Supplee,Ronen Marmorstein,Kathryn E Wellen","doi":"10.1016/j.tem.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.002","url":null,"abstract":"Disorders of lipid metabolism, including hyperlipidemia, atherosclerosis, and metabolic dysfunction-associated steatotic liver disease, are increasing across the globe. Bempedoic acid (BPA) is a first-in-class drug for the treatment of hypercholesterolemia and cardiac risk reduction, which may particularly benefit those who do not tolerate statins. Inhibition of hepatic ATP-citrate lyase (ACLY) is widely accepted as the main mediator of its observed clinical effects. However, BPA treatment also has ACLY-independent effects on lipid metabolism, as the structural similarity of BPA to endogenous fatty acids allows it to trigger multiple lipid-signaling pathways. Here, we review the molecular targets of BPA and related 'decoy fatty acid' drugs and identify areas where further study is warranted as these molecules are evaluated for clinical indications.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932594","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}
Pub Date : 2025-05-07DOI: 10.1016/j.tem.2025.04.004
Saurabh Kumar Gupta,Tina Rawal,Monika Arora
Non-communicable diseases (NCDs) pose a serious challenge to global public health, compounded by unhealthy nutrition and obesogenic environments. This science and society article emphasizes several evidence-based behavior-change strategies, policy interventions, and meaningful youth engagement to promote healthy nutrition choices among children and adolescents.
{"title":"Healthy choices, healthy futures: promoting healthy nutrition to curb non-communicable diseases.","authors":"Saurabh Kumar Gupta,Tina Rawal,Monika Arora","doi":"10.1016/j.tem.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.004","url":null,"abstract":"Non-communicable diseases (NCDs) pose a serious challenge to global public health, compounded by unhealthy nutrition and obesogenic environments. This science and society article emphasizes several evidence-based behavior-change strategies, policy interventions, and meaningful youth engagement to promote healthy nutrition choices among children and adolescents.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926444","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}
Pub Date : 2025-05-05DOI: 10.1016/j.tem.2025.04.003
Céline Van Dender,Jolien Vandewalle,Claude Libert
Transcription factor hepatocyte nuclear factor 4 alpha (HNF4α) is considered the master regulator of hepatocyte differentiation. During homeostasis, HNF4α maintains liver identity by supporting metabolism while inhibiting proliferation. It is downregulated in response to both acute and chronic insults; however, although this supports hepatic regeneration in mild acute settings, severe or chronic downregulation may further compromise liver function and lead to a lethal outcome. Here, we provide an overview of liver diseases associated with downregulation, altered expression, or dysfunction of HNF4α and suggest the potential underlying mechanisms. We further propose that therapy with Hnf4a mRNA or HNF4α agonists to reactivate HNF4α may be beneficial in pathophysiological contexts characterized by loss of liver function.
{"title":"Balancing metabolism and regeneration in liver diseases through HNF4α targeting.","authors":"Céline Van Dender,Jolien Vandewalle,Claude Libert","doi":"10.1016/j.tem.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.003","url":null,"abstract":"Transcription factor hepatocyte nuclear factor 4 alpha (HNF4α) is considered the master regulator of hepatocyte differentiation. During homeostasis, HNF4α maintains liver identity by supporting metabolism while inhibiting proliferation. It is downregulated in response to both acute and chronic insults; however, although this supports hepatic regeneration in mild acute settings, severe or chronic downregulation may further compromise liver function and lead to a lethal outcome. Here, we provide an overview of liver diseases associated with downregulation, altered expression, or dysfunction of HNF4α and suggest the potential underlying mechanisms. We further propose that therapy with Hnf4a mRNA or HNF4α agonists to reactivate HNF4α may be beneficial in pathophysiological contexts characterized by loss of liver function.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915214","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：