Pub Date : 2025-05-01DOI: 10.1016/j.tem.2025.04.005
Shuqin Zeng,Shaopu Wang,Dezhi Mu
Establishment of the early-life gut microbiome, coinciding with the host development, predisposes to long-term disease risk if disrupted. Recently, Hill et al. precisely delineated a critical early-life window in humans and mice during which specific fungi and bacteria play indispensable roles in β-cell development, thereby regulating lifelong metabolic homeostasis.
{"title":"Seeding microbes in defined early-life windows to fight diabetes.","authors":"Shuqin Zeng,Shaopu Wang,Dezhi Mu","doi":"10.1016/j.tem.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.tem.2025.04.005","url":null,"abstract":"Establishment of the early-life gut microbiome, coinciding with the host development, predisposes to long-term disease risk if disrupted. Recently, Hill et al. precisely delineated a critical early-life window in humans and mice during which specific fungi and bacteria play indispensable roles in β-cell development, thereby regulating lifelong metabolic homeostasis.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903106","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 : 2025-04-25DOI: 10.1016/j.tem.2025.03.013
Christian Dölle,Charalampos Tzoulis
Neurodegenerative diseases (NDDs) pose a significant and rapidly growing global health challenge, but there are no effective therapies to delay or halt progression. In recent years augmentation of nicotinamide adenine dinucleotide (NAD) has emerged as a promising disease-modifying strategy that targets multiple key disease pathways across multiple NDDs, such as mitochondrial dysfunction, energy deficits, proteostasis, and neuroinflammation. Several early clinical trials of NAD augmentation have been completed, and many more are currently underway, reflecting the growing optimism and urgency within the field. We discuss the rationale and evolving therapeutic landscape of NAD augmentation. We argue that, to fully realize its therapeutic potential, it is essential to determine the specific contexts in which NAD supplementation is most effective and to address crucial knowledge gaps.
{"title":"NAD augmentation as a disease-modifying strategy for neurodegeneration.","authors":"Christian Dölle,Charalampos Tzoulis","doi":"10.1016/j.tem.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.013","url":null,"abstract":"Neurodegenerative diseases (NDDs) pose a significant and rapidly growing global health challenge, but there are no effective therapies to delay or halt progression. In recent years augmentation of nicotinamide adenine dinucleotide (NAD) has emerged as a promising disease-modifying strategy that targets multiple key disease pathways across multiple NDDs, such as mitochondrial dysfunction, energy deficits, proteostasis, and neuroinflammation. Several early clinical trials of NAD augmentation have been completed, and many more are currently underway, reflecting the growing optimism and urgency within the field. We discuss the rationale and evolving therapeutic landscape of NAD augmentation. We argue that, to fully realize its therapeutic potential, it is essential to determine the specific contexts in which NAD supplementation is most effective and to address crucial knowledge gaps.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885542","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}
Endometriosis, characterized by uterine-like tissue growth outside the uterus, is a complex disorder with significant clinical implications. This review explores how body composition - both low body mass index (BMI) and obesity - modulates endometriosis progression through metabolic, hormonal, and immune-inflammatory pathways. Obesity-driven leptin signaling emerges as a pivotal link, promoting systemic inflammation, angiogenesis, and lesion persistence via Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Shared molecular mechanisms between endometriosis and obesity highlight opportunities for precision medicine and targeted therapies. By addressing leptin-driven pathways and metabolic dysfunction, we introduce innovative strategies, offering novel insights into the improved management of this multifaceted condition.
{"title":"The interplay between endometriosis and obesity.","authors":"Md Saidur Rahman,Yunjeong Park,Hossein Hosseinirad,Jung-Ho Shin,Jae-Wook Jeong","doi":"10.1016/j.tem.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.011","url":null,"abstract":"Endometriosis, characterized by uterine-like tissue growth outside the uterus, is a complex disorder with significant clinical implications. This review explores how body composition - both low body mass index (BMI) and obesity - modulates endometriosis progression through metabolic, hormonal, and immune-inflammatory pathways. Obesity-driven leptin signaling emerges as a pivotal link, promoting systemic inflammation, angiogenesis, and lesion persistence via Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Shared molecular mechanisms between endometriosis and obesity highlight opportunities for precision medicine and targeted therapies. By addressing leptin-driven pathways and metabolic dysfunction, we introduce innovative strategies, offering novel insights into the improved management of this multifaceted condition.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885081","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 : 2025-04-24DOI: 10.1016/j.tem.2025.03.014
Dewei Kong,Oliwia Kowalik,Emma Garratt,Keith M Godfrey,Shiao-Yng Chan,Adrian Kee Keong Teo
Gestational diabetes mellitus (GDM) is a common pregnancy complication and a risk factor for the subsequent development of type 2 diabetes (T2D) in mothers and of several metabolic diseases in offspring. However, the molecular underpinnings of these risks are not well understood. Genome-wide association studies (GWAS) and epigenetic studies may provide complementary insights into the causal relationships between GDM exposure and maternal/offspring metabolic outcomes. In this review we discuss the potential pathophysiological roles of specific genetic variants and commonly reported differentially methylated loci in GDM development, and their link to the progression to T2D in both the mother and the offspring in later life, pointing to the potential for tailored interventional strategies based on these genetic and epigenetic mechanisms.
{"title":"Genetics and epigenetics in gestational diabetes contributing to type 2 diabetes.","authors":"Dewei Kong,Oliwia Kowalik,Emma Garratt,Keith M Godfrey,Shiao-Yng Chan,Adrian Kee Keong Teo","doi":"10.1016/j.tem.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.014","url":null,"abstract":"Gestational diabetes mellitus (GDM) is a common pregnancy complication and a risk factor for the subsequent development of type 2 diabetes (T2D) in mothers and of several metabolic diseases in offspring. However, the molecular underpinnings of these risks are not well understood. Genome-wide association studies (GWAS) and epigenetic studies may provide complementary insights into the causal relationships between GDM exposure and maternal/offspring metabolic outcomes. In this review we discuss the potential pathophysiological roles of specific genetic variants and commonly reported differentially methylated loci in GDM development, and their link to the progression to T2D in both the mother and the offspring in later life, pointing to the potential for tailored interventional strategies based on these genetic and epigenetic mechanisms.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884993","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 : 2025-04-24DOI: 10.1016/j.tem.2025.03.015
Salil V Deo,Naveed A Sattar
Investigating the association between glucagon-like peptide 1 receptor agonists (GLP1-RAs) and incident disease across 175 health outcomes in US Veterans with diabetes, Xie et al. recently reported lower risk for cardiokidney disease and substance use disorders, but higher risk for pancreatitis, gastrointestinal disorders, and arthritis. However, many apparent novel findings need testing or validation in randomized trials.
{"title":"Promising results but caution needed in GLP-1RA large scale epidemiology.","authors":"Salil V Deo,Naveed A Sattar","doi":"10.1016/j.tem.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.015","url":null,"abstract":"Investigating the association between glucagon-like peptide 1 receptor agonists (GLP1-RAs) and incident disease across 175 health outcomes in US Veterans with diabetes, Xie et al. recently reported lower risk for cardiokidney disease and substance use disorders, but higher risk for pancreatitis, gastrointestinal disorders, and arthritis. However, many apparent novel findings need testing or validation in randomized trials.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885080","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 : 2025-04-16DOI: 10.1016/j.tem.2025.03.012
Jara Pérez-Jiménez,Yolanda Sanz,Rosa M Lamuela-Raventós
{"title":"(Poly)phenols as bioactive constituents linked to dietary fibre metabolic fate.","authors":"Jara Pérez-Jiménez,Yolanda Sanz,Rosa M Lamuela-Raventós","doi":"10.1016/j.tem.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.012","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849361","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 : 2025-04-16DOI: 10.1016/j.tem.2025.03.008
Jie Cheng,Yifeng Xiao,Peng Jiang
Fumarate is a key metabolite produced primarily by the tricarboxylic acid (TCA) and urea cycles. In addition to having a metabolic role, its electrophilicity enables it to covalently modify cysteines; moreover, because of its α-ketoglutarate (α-KG)-like structure, it can also act as a competitive inhibitor of α-KG-dependent dioxygenases for epigenetic remodeling. Recent advances have broadened the role of fumarate as a bridge between metabolism and both innate and adaptive immunity, suggesting potentially important functions in anticancer immunity and autoimmune diseases. Here we review the connections between fumarate metabolism and immunity; we describe the mechanisms of fumarate regulation in cancer, autoimmunity, and other diseases; and we explore the clinical implications of fumarate and its esters for immunotherapy.
{"title":"Fumarate integrates metabolism and immunity in diseases.","authors":"Jie Cheng,Yifeng Xiao,Peng Jiang","doi":"10.1016/j.tem.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.008","url":null,"abstract":"Fumarate is a key metabolite produced primarily by the tricarboxylic acid (TCA) and urea cycles. In addition to having a metabolic role, its electrophilicity enables it to covalently modify cysteines; moreover, because of its α-ketoglutarate (α-KG)-like structure, it can also act as a competitive inhibitor of α-KG-dependent dioxygenases for epigenetic remodeling. Recent advances have broadened the role of fumarate as a bridge between metabolism and both innate and adaptive immunity, suggesting potentially important functions in anticancer immunity and autoimmune diseases. Here we review the connections between fumarate metabolism and immunity; we describe the mechanisms of fumarate regulation in cancer, autoimmunity, and other diseases; and we explore the clinical implications of fumarate and its esters for immunotherapy.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849360","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 : 2025-04-14DOI: 10.1016/j.tem.2025.03.010
Lingling Wang,Qingyi Jia,Jinhan He,Yanping Li
The increasing global prevalence of obesity presents a substantial challenge to public health. Current nutrient-stimulated hormone (NuSH)-based therapeutics are hindered by receptor desensitization, muscle loss, and weight regain. The adipose tissue, the primary organ responsible for energy storage and metabolic management, is a promising target for obesity treatment. Nanomedicine holds promise to precisely deliver medication to the adipose tissue to maximize therapeutic efficacy and minimize off-target effects; indeed, various adipose tissue-targeting nanomedicines have shown impressive anti-obesity effects by optimizing drug pharmacokinetic profiles and reducing nonspecific distribution in preclinical studies. Here we examine the current state of the art of adipose tissue-targeting nanomedicines, offering insights into recent advances, future possibilities, and the remaining challenges associated with their application in obesity treatment.
{"title":"Adipose tissue-targeting nanomedicines for obesity pharmacotherapy.","authors":"Lingling Wang,Qingyi Jia,Jinhan He,Yanping Li","doi":"10.1016/j.tem.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.010","url":null,"abstract":"The increasing global prevalence of obesity presents a substantial challenge to public health. Current nutrient-stimulated hormone (NuSH)-based therapeutics are hindered by receptor desensitization, muscle loss, and weight regain. The adipose tissue, the primary organ responsible for energy storage and metabolic management, is a promising target for obesity treatment. Nanomedicine holds promise to precisely deliver medication to the adipose tissue to maximize therapeutic efficacy and minimize off-target effects; indeed, various adipose tissue-targeting nanomedicines have shown impressive anti-obesity effects by optimizing drug pharmacokinetic profiles and reducing nonspecific distribution in preclinical studies. Here we examine the current state of the art of adipose tissue-targeting nanomedicines, offering insights into recent advances, future possibilities, and the remaining challenges associated with their application in obesity treatment.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841261","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 : 2025-04-11DOI: 10.1016/j.tem.2025.03.009
Meng Yuan, Mengnan Shi, Hong Yang, Sajda Ashraf, Shazia Iqbal, Hasan Turkez, Jan Boren, Cheng Zhang, Mathias Uhlén, Ozlem Altay, Adil Mardinoglu
Pyruvate kinase is a key regulator in hepatic glucose metabolism, encoded by the gene pyruvate kinase liver/red blood cells (PKLR). Systems biology-based approaches, including metabolic and gene co-expression networks analyses, as well as genome-wide association studies (GWAS), have led to the identification of PKLR as a pivotal gene influencing liver metabolism in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). Here, we review the critical role of PKLR in MASLD and HCC progression and examine the effects of PKLR modulation both in vitro and in vivo. We also discuss the development of therapeutic strategies for patients with MASLD and HCC by modulating PKLR, highlighting its promising future in a broader range of liver diseases.
{"title":"Targeting PKLR in liver diseases","authors":"Meng Yuan, Mengnan Shi, Hong Yang, Sajda Ashraf, Shazia Iqbal, Hasan Turkez, Jan Boren, Cheng Zhang, Mathias Uhlén, Ozlem Altay, Adil Mardinoglu","doi":"10.1016/j.tem.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.009","url":null,"abstract":"Pyruvate kinase is a key regulator in hepatic glucose metabolism, encoded by the gene pyruvate kinase liver/red blood cells (<ce:italic>PKLR</ce:italic>). Systems biology-based approaches, including metabolic and gene co-expression networks analyses, as well as genome-wide association studies (GWAS), have led to the identification of <ce:italic>PKLR</ce:italic> as a pivotal gene influencing liver metabolism in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). Here, we review the critical role of <ce:italic>PKLR</ce:italic> in MASLD and HCC progression and examine the effects of <ce:italic>PKLR</ce:italic> modulation both <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic>. We also discuss the development of therapeutic strategies for patients with MASLD and HCC by modulating <ce:italic>PKLR</ce:italic>, highlighting its promising future in a broader range of liver diseases.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849491","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 : 2025-04-10DOI: 10.1016/j.tem.2025.03.006
Bryan A Priego-Parra,Rocío Gallego-Durán,Berenice M Román-Calleja,José Antonio Velarde-Ruiz Velasco,Manuel Romero-Gómez,Jordi Gracia-Sancho
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a pressing global health concern. The complexity of MASLD and the lack of universally effective treatments expose the limitations of current interventions, which focus mainly on lifestyle modifications. Here, we explore the multilayered nature of MASLD, emphasizing its pathophysiology in shaping future medical and lifestyle interventions from a personalized medicine perspective, based on individual molecular profiles. Additionally, we address the limitations of current animal models in reflecting human metabolic syndrome and sex-specific differences. We argue that a holistic approach, integrating social determinants of health, patient preferences, and adherence patterns, is essential for advancing MASLD management effectively.
{"title":"Advancing precision medicine in metabolic dysfunction-associated steatotic liver disease.","authors":"Bryan A Priego-Parra,Rocío Gallego-Durán,Berenice M Román-Calleja,José Antonio Velarde-Ruiz Velasco,Manuel Romero-Gómez,Jordi Gracia-Sancho","doi":"10.1016/j.tem.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.tem.2025.03.006","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a pressing global health concern. The complexity of MASLD and the lack of universally effective treatments expose the limitations of current interventions, which focus mainly on lifestyle modifications. Here, we explore the multilayered nature of MASLD, emphasizing its pathophysiology in shaping future medical and lifestyle interventions from a personalized medicine perspective, based on individual molecular profiles. Additionally, we address the limitations of current animal models in reflecting human metabolic syndrome and sex-specific differences. We argue that a holistic approach, integrating social determinants of health, patient preferences, and adherence patterns, is essential for advancing MASLD management effectively.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827116","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}
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