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Molecular targets of bempedoic acid and related decoy fatty acids. 苯二甲酸及相关诱饵脂肪酸的分子靶点。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-08 DOI: 10.1016/j.tem.2025.04.002
Julianna G Supplee,Ronen Marmorstein,Kathryn E Wellen
{"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}
引用次数: 0
Healthy choices, healthy futures: promoting healthy nutrition to curb non-communicable diseases. 健康的选择，健康的未来：促进健康营养，遏制非传染性疾病。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-07 DOI: 10.1016/j.tem.2025.04.004
Saurabh Kumar Gupta,Tina Rawal,Monika Arora
{"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}
引用次数: 0
Balancing metabolism and regeneration in liver diseases through HNF4α targeting. 通过靶向HNF4α平衡肝脏疾病的代谢和再生。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-05 DOI: 10.1016/j.tem.2025.04.003
Céline Van Dender,Jolien Vandewalle,Claude Libert
{"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}
引用次数: 0
Seeding microbes in defined early-life windows to fight diabetes. 在确定的生命早期窗口中播种微生物以对抗糖尿病。
Trends in Endocrinology & Metabolism Pub Date : 2025-05-01 DOI: 10.1016/j.tem.2025.04.005
Shuqin Zeng,Shaopu Wang,Dezhi Mu
{"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}
引用次数: 0
NAD augmentation as a disease-modifying strategy for neurodegeneration. NAD增强作为神经退行性疾病的一种改善策略。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-25 DOI: 10.1016/j.tem.2025.03.013
Christian Dölle,Charalampos Tzoulis
{"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}
引用次数: 0
The interplay between endometriosis and obesity. 子宫内膜异位症和肥胖之间的相互作用。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-24 DOI: 10.1016/j.tem.2025.03.011
Md Saidur Rahman,Yunjeong Park,Hossein Hosseinirad,Jung-Ho Shin,Jae-Wook Jeong
{"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}
引用次数: 0
Genetics and epigenetics in gestational diabetes contributing to type 2 diabetes. 妊娠期糖尿病与2型糖尿病的遗传学和表观遗传学关系。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-24 DOI: 10.1016/j.tem.2025.03.014
Dewei Kong,Oliwia Kowalik,Emma Garratt,Keith M Godfrey,Shiao-Yng Chan,Adrian Kee Keong Teo
{"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}
引用次数: 0
Promising results but caution needed in GLP-1RA large scale epidemiology. 有希望的结果，但需要谨慎的GLP-1RA大规模流行病学。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-24 DOI: 10.1016/j.tem.2025.03.015
Salil V Deo,Naveed A Sattar
{"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}
引用次数: 0
(Poly)phenols as bioactive constituents linked to dietary fibre metabolic fate. （聚）酚作为与膳食纤维代谢命运相关的生物活性成分。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-16 DOI: 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}
引用次数: 0
Fumarate integrates metabolism and immunity in diseases. 富马酸在疾病中整合代谢和免疫。
Trends in Endocrinology & Metabolism Pub Date : 2025-04-16 DOI: 10.1016/j.tem.2025.03.008
Jie Cheng,Yifeng Xiao,Peng Jiang
{"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}
引用次数: 0
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