Metabolism: clinical and experimental最新文献

{"title":"ALDH2 deficiency aggravates vascular injury-induced restenosis by enhancing vascular smooth muscle cell proliferation through SLC38A2-mediated upregulation of glutamine uptake","authors":"Dehui Hou ,&nbsp;Kehui Yang ,&nbsp;Yang Liu,&nbsp;Han Du,&nbsp;Hongwei Yue,&nbsp;Fengyang Xu,&nbsp;Wentao Sang,&nbsp;Xiangkai Zhao,&nbsp;Yijun Sun,&nbsp;Feng Xu,&nbsp;Yuguo Chen","doi":"10.1016/j.metabol.2025.156411","DOIUrl":"10.1016/j.metabol.2025.156411","url":null,"abstract":"<div><h3>Background and aims</h3><div>Vascular injury-induced restenosis is an important cause of poor long-term prognosis in patients with coronary artery disease (CAD). Although aldehyde dehydrogenase 2 (ALDH2) deficiency has been linked to poor outcomes in CAD patients, the precise mechanisms through which ALDH2 influences vascular injury-induced restenosis remain elusive. Herein, we attempted to explore the role of ALDH2 in modulating vascular smooth muscle cell (VSMC) proliferation and vascular injury-induced restenosis.</div></div><div><h3>Methods and results</h3><div>Immunofluorescence and immunoblotting revealed that ALDH2 expression was significantly decreased in VSMCs in human stenotic coronary segments and injured mouse femoral and carotid arteries. Global ALDH2 knockout and VSMC-specific ALDH2 knockout exacerbated injury-induced neointima formation, whereas VSMC-specific ALDH2 overexpression reduced neointima formation. Endothelial cell (EC)-specific ALDH2 knockout had little effect on injury-induced neointima formation. Mechanistic studies revealed that ALDH2 deficiency facilitated VSMC proliferation by upregulating the expression of the glutamine transporter SLC38A2, which is a novel ALDH2 target gene. Further bioinformatics analysis, luciferase assays, and ChIP–qPCR revealed that ALDH2 deficiency increased SLC38A2 expression <em>via</em> activating transcription factor 4 (ATF4) and that ATF4 knockdown largely reversed the ability of ALDH2 deficiency to promote VSMC proliferation. Moreover, ALDH2 deficiency promoted the accumulation of 4-HNE adducted proteins, thereby activating ATF4, which subsequently increased SLC28A2 transcriptional activity in VSMCs. Importantly, downregulation of SLC38A2 by adeno-associated virus serotype 2 (AAV2) shRNA or by the inhibitor MeAIB has promising therapeutic potential in limiting VSMC proliferation and neointima formation. Finally, we demonstrated that VSMC proliferation was aggravated and that neointima formation occurred in ALDH2^E506k mutant mice.</div></div><div><h3>Conclusion</h3><div>Our study elucidates a novel mechanism through which ALDH2 deficiency aggravates neointimal formation by enhancing VSMC proliferation through an increase in glutamine uptake, suggesting a promising translational strategy for the prevention of vascular injury-induced restenosis.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156411"},"PeriodicalIF":11.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258767","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":"Mitochondrial phosphopantetheinylation is required for oxidative metabolism","authors":"Pieter R. Norden ,&nbsp;Riley J. Wedan ,&nbsp;Samuel E.J. Preston ,&nbsp;Morgan Canfield ,&nbsp;Naomi Graber ,&nbsp;Jacob Z. Longenecker ,&nbsp;Olivia A. Pentecost ,&nbsp;Elizabeth McLaughlin ,&nbsp;Madeleine L. Hart ,&nbsp;Sara M. Nowinski","doi":"10.1016/j.metabol.2025.156413","DOIUrl":"10.1016/j.metabol.2025.156413","url":null,"abstract":"<div><div>4′-Phosphopantetheinyl (4’PP) groups are essential co-factors added to target proteins by <u>p</u>hospho<u>p</u>antetheinyl <u>t</u>ransferase (PPTase) enzymes. Although mitochondrial 4’PP-modified proteins have been described for decades, a mitochondrially-localized PPTase has never been found in mammals. We discovered that the cytoplasmic PPTase <u>a</u>mino<u>a</u>dipate <u>s</u>emialdehyde <u>d</u>ehydrogenase <u>p</u>hospho<u>p</u>antetheinyl <u>t</u>ransferase (AASDHPPT) is required for mitochondrial respiration and oxidative metabolism. Loss of AASDHPPT results in failed 4’PP modification of the mitochondrial acyl carrier protein and blunted activity of the mitochondrial fatty acid synthesis (mtFAS) pathway. We found that in addition to its cytoplasmic localization, AASDHPPT localizes to the mitochondrial matrix via an N-terminal mitochondrial targeting sequence contained within the first 20 amino acids of the protein. Our data show that this novel mitochondrial localization of AASDHPPT is required to support mtFAS activity and oxidative metabolism. We further identify five variants of uncertain significance in <em>AASDHPPT</em> that are likely pathogenic in humans due to loss of mtFAS activity.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156413"},"PeriodicalIF":11.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251663","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":"Phenome-wide associations of coffee intake in the human phenotype project","authors":"Jin Dai ,&nbsp;Wen Dai ,&nbsp;Yoriko Heianza ,&nbsp;Lu Qi","doi":"10.1016/j.metabol.2025.156412","DOIUrl":"10.1016/j.metabol.2025.156412","url":null,"abstract":"<div><h3>Objective</h3><div>Coffee is one of the most widely consumed beverages globally and has been linked to favorable health outcomes. However, its system-wide relationships with human biology and the underlying mechanisms remain poorly characterized. This study aimed to investigate the relationship between coffee consumption and continuous glucose monitoring (CGM) metrics and other biological systems in healthy adults.</div></div><div><h3>Research design and methods</h3><div>In the Human Phenotype Project, 8666 generally healthy Israeli adults provided two weeks of real-time dietary logs, from which coffee intake was estimated. Participants wore CGM devices throughout this period, and multimodal data spanning 11 additional systems (e.g., gut microbiome, serum lipidomics, and body composition) were collected. We employed machine learning approaches to quantify the extent to which each system reflected coffee intake. We performed linear regression to identify individual traits associated with coffee intake, with false discovery rates &lt; 0.05 considered significant.</div></div><div><h3>Results</h3><div>This cross-sectional study identified continuously-monitored glucose regulation and gut microbial composition as the most reflective systems of coffee intake, with further analyses revealing favorable glycemic profiles spanning diverse aspects of glucose regulation with increasing coffee intake, and <em>Clostridium phoceensis</em> (i.e., <em>Lawsonibacter asaccharolyticus</em>) as the most significant species positively associated with coffee intake. Additionally, coffee intake was favorably associated with traits across body composition, serum lipidomics, and hepatic, hematopoietic, and renal systems.</div></div><div><h3>Conclusions</h3><div>This study found that habitual coffee intake was linked to multifaceted favorable glucose control captured by CGM and favorable profiles across multiple biological systems, providing mechanistic insights that may guide precision nutrition strategies for diabetes prevention.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156412"},"PeriodicalIF":11.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232946","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":"Semaglutide, the first approved GLP-1 receptor agonist for the management of metabolic dysfunction-associated steatohepatitis","authors":"Chrysoula Boutari ,&nbsp;Michael A. Hill ,&nbsp;Christos S. Mantzoros","doi":"10.1016/j.metabol.2025.156397","DOIUrl":"10.1016/j.metabol.2025.156397","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156397"},"PeriodicalIF":11.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232989","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":"Administration of the KCa channel activator SKA-31 improves long-term endothelial function, blood pressure regulation and cardiac performance in rats with type 2 diabetes","authors":"Ramesh C. Mishra ,&nbsp;Rayan Khaddaj Mallat ,&nbsp;Cini M. John ,&nbsp;Darrell D. Belke ,&nbsp;Liam Hamm ,&nbsp;Latika Singh ,&nbsp;Taeyoeb Kim ,&nbsp;Grace George ,&nbsp;Yong-Xiang Chen ,&nbsp;Heike Wulff ,&nbsp;Andrew P. Braun","doi":"10.1016/j.metabol.2025.156410","DOIUrl":"10.1016/j.metabol.2025.156410","url":null,"abstract":"<div><h3>Objective</h3><div>Our goal in the present study was to examine whether long-term administration of the selective K_Ca channel activator SKA-31 would mitigate the development/severity of type 2 diabetes (T2D)-associated cardiovascular (CV) complications in adult male Goto-Kakizaki (GK) rats with spontaneous T2D.</div></div><div><h3>Methods</h3><div>Adult male T2D GK rats instrumented with radio-telemeters were administered either vehicle or the K_Ca channel activator SKA-31 (10 mg/kg) at ~14 weeks of age by daily intraperitoneal injection for 12 consecutive weeks. <em>In vivo</em> and <em>ex vivo</em> analyses of CV function, immune system status, vascular signaling and metabolic hormones were performed following treatment.</div></div><div><h3>Results</h3><div>Vehicle-treated T2D GK rats exhibited gradual increases in systolic and diastolic blood pressure, whereas SKA-31 administration led to lower mean arterial pressure, along with improvements in cardiac function (i.e., ejection fraction, fractional shortening) and structure (i.e., end systolic and diastolic volumes), as determined by echocardiography. SKA-31 treatment <em>in vivo</em> further improved vascular endothelial function in small mesenteric arteries, as determined by arterial pressure myography, and increased the protein expression of vasodilatory signaling molecules in the vascular wall. Prolonged SKA-31 treatment did not impair vasodilatory responsiveness in skeletal muscle and coronary arteries, elicit a pro-inflammatory profile in T2D GK rats or produce any adverse histological effects in brain, kidney or liver.</div></div><div><h3>Conclusions</h3><div>The results of our study demonstrate that low-dose administration of the K_Ca channel activator SKA-31 improved CV function in an established rat model of spontaneous T2D and reveal a potential novel strategy to oppose CV-related morbidity in T2D.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156410"},"PeriodicalIF":11.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225658","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":"Emerging roles of TRIM in metabolic regulation","authors":"Jiaxing Wang ,&nbsp;Qiangzhou Wang ,&nbsp;Xinrui Li ,&nbsp;Qingqing Cai ,&nbsp;Yulin Bi ,&nbsp;Chenyang Xu ,&nbsp;Hao Bai ,&nbsp;Lihong Gu ,&nbsp;Guobin Chang ,&nbsp;Shihao Chen","doi":"10.1016/j.metabol.2025.156394","DOIUrl":"10.1016/j.metabol.2025.156394","url":null,"abstract":"<div><div>Recent findings have broadened our understanding of the tripartite motif (TRIM) protein family, positioning these proteins as pivotal regulators of cellular metabolism and cell fate. Primarily functioning as versatile E3 ubiquitin ligases, TRIM proteins orchestrate key metabolic pathways—including glucose, lipid, and amino acid metabolism—through both ubiquitination-dependent and -independent mechanisms such as oligomerization and epigenetic modification. For example, TRIM38, TRIM11, and TRIM24 have been reported to modulate glycolytic flux and insulin signaling by targeting key glucose transporters and glycolytic enzymes, with effects on cancer metabolism and insulin responses in model systems. Similarly, TRIM21 and TRIM56 have been implicated in fatty acid synthesis, oxidation, and cholesterol balance, with potential relevance to fatty-liver conditions and atherosclerosis. Moreover, TRIM-mediated regulation of amino acid metabolism-particularly through pathways involving glutamine and branched-chain amino acids-plays a central role in tumor metabolic reprogramming and survival. Beyond enzymatic regulation, TRIM proteins exert non-canonical functions through epigenetic modulation and interactions with signaling networks. This review synthesizes current insights into the multifaceted roles of TRIM proteins in metabolic control and cell death, suggesting that ferroptosis may link TRIM proteins to lipid and amino acid metabolism, and highlights the connection between TRIM proteins and metabolic stress as a key area for future research.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156394"},"PeriodicalIF":11.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109903","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":"BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity","authors":"Morgane A. Philippe ,&nbsp;Blandine Fruchet ,&nbsp;Lucie Cagninacci ,&nbsp;Lucie Beaudoin ,&nbsp;Alexis Gadault ,&nbsp;Bastien Aznar ,&nbsp;Nicolas Venteclef ,&nbsp;Etienne Challet ,&nbsp;Agnès Lehuen ,&nbsp;Ute C. Rogner ,&nbsp;Amine Toubal","doi":"10.1016/j.metabol.2025.156396","DOIUrl":"10.1016/j.metabol.2025.156396","url":null,"abstract":"<div><div>Contemporary lifestyle modifications such as changes in nutritional and sleep/wake rhythms increase the risk of metabolic and inflammatory complications linked to obesity, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). BMAL2 (Brain and Muscle ARNT Like Protein 2) is a transcription factor belonging to the circadian clock transcriptional feedback loop which synchronizes internal biological rhythms to environment. In humans, reduced expression in white adipose tissue (WAT) and specific polymorphisms of <em>BMAL2</em> are associated with obesity and T2D. In this study we report that <em>Bmal2</em> deletion in mice leads to increased body weight gain during diet-induced obesity. Loss of BMAL2 triggers the inflammatory response by increasing <em>Tnfα</em> expression and modifying adipocyte progenitor fate. This results in reduced lipid storage capacity within the WAT and increased ectopic storage in the liver. These functional and structural alterations culminate in the onset of hepatic steatosis and insulin resistance in liver and WAT. Overall, our investigations underscore the role of BMAL2 in the development and function of adipocytes, as well as in their inflammatory potential within the WAT. Our findings contribute to the understanding of the role of circadian clock genes in obesity and interconnected metabolic complications.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156396"},"PeriodicalIF":11.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124807","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":"Enhancing cardiac serine biosynthesis mitigates the progression of dilated cardiomyopathy in mice","authors":"Maryam Kay ,&nbsp;Anne-Maj Samuelsson ,&nbsp;Nike Bharucha ,&nbsp;Xueyi Li ,&nbsp;Rohin Ramchandani ,&nbsp;Rachel E. Baum ,&nbsp;Diego Ruiz Arvizo ,&nbsp;Aurélie Laguerre ,&nbsp;Sherin Lajevardi ,&nbsp;Shrikaar Kambhampati ,&nbsp;Christian M. Metallo ,&nbsp;Michael S. Kapiloff ,&nbsp;Ioannis Karakikes","doi":"10.1016/j.metabol.2025.156395","DOIUrl":"10.1016/j.metabol.2025.156395","url":null,"abstract":"<div><div>Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. However, disease-modifying therapies remain limited. Metabolic dysfunction has emerged as a key driver of DCM pathogenesis, and impaired serine biosynthesis, catalyzed by the rate-limiting enzyme phosphoglycerate dehydrogenase (PHGDH), has recently been identified as a potential therapeutic target. Here, we evaluated the therapeutic potential of increasing serine biosynthesis through AAV9-mediated PHGDH gene augmentation in a transgenic TM54 mouse model of DCM with established pathology. Longitudinal echocardiography showed preserved systolic function and prevented ventricular dilatation in TM54 mice treated with AAV9-PHGDH compared to AAV9-GFP controls. Histological analysis revealed reduced myocardial fibrosis and cardiomyocyte hypertrophy in AAV9-PHGDH-treated TM54 hearts, indicating a reversal of pathological remodeling. Metabolic profiling, including targeted metabolomics and in vivo ¹³C-glucose tracing analysis, revealed that serine levels increased in hearts treated with AAV9-PHGDH, accompanied by decreases in glucose-derived pyruvate and lactate. At the same time, mitochondrial oxidative metabolism remained intact, indicating a shift of glycolytic carbon towards serine biosynthesis. Collectively, these findings show that enhancing cardiac serine synthesis through PHGDH gene augmentation therapy preserves contractile function and mitigates disease progression in vivo, suggesting a novel metabolic therapeutic strategy for DCM.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156395"},"PeriodicalIF":11.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102795","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":"Sepsis-induced lipid droplet accumulation enhances antibacterial innate immunity through mechanisms dependent on DGAT-1 and interferon-beta","authors":"Filipe S. Pereira-Dutra ,&nbsp;Julia Cunha Santos ,&nbsp;Ellen Kiarely Souza ,&nbsp;Rodrigo Vieira Savi ,&nbsp;Tamyris S. Souza ,&nbsp;Helen Gil ,&nbsp;Hugo Espinheira-Silva ,&nbsp;Felipe Ferraro-Moreira ,&nbsp;Guilherme Iack ,&nbsp;Tamires Cunha-Fernandes ,&nbsp;Tathiany Igreja-Silva ,&nbsp;Lohanna Palhinha ,&nbsp;Mariana Macedo Campos ,&nbsp;Ester Fernanda Terra Souza ,&nbsp;Amanda França Cordeiro ,&nbsp;Pablo Andrade-dos-Santos ,&nbsp;Douglas Mathias Oliveira ,&nbsp;Vinicius Soares Cardoso ,&nbsp;Matheus A. Rajão ,&nbsp;Livia Teixeira ,&nbsp;Patrícia T. Bozza","doi":"10.1016/j.metabol.2025.156389","DOIUrl":"10.1016/j.metabol.2025.156389","url":null,"abstract":"<div><div>Lipid droplets (LDs) are lipid-rich organelles recognized as central players in lipid homeostasis, signaling, and inflammation. While their functions in inflammation are well-documented, the mechanisms of LDs in antibacterial immunity and infection resistance remain less understood. Our results show that <em>E. coli</em>-infection trigger immunometabolic reprogramming and LD accumulation in murine macrophages (BMDM). Moreover, purified LDs from LPS-stimulated and <em>E. coli-</em>infected macrophages exhibited direct <em>E. coli</em> anti-bacterial activity. Pharmacological inhibition or genetic knockdown of DGAT1, a key enzyme in triglyceride synthesis, reduced LD formation, bacterial clearance, and pro-inflammatory responses (nitric oxide, PGE₂, CCL2, IL-6). Notably, DGAT1 inhibition impaired the expression of IFN-β and interferon-stimulated genes (ISGs), including viperin, iNOS, cathelicidin and IGTP, in <em>E. coli</em>-infected macrophages. In a cecal-ligation and puncture model of sepsis in C57BL/6 mice, DGAT1 inhibition reduced sepsis-induced LD accumulation in peritoneal cells and decreased levels of IFN-β, CCL2, nitric oxide, and lipid mediators (PGE₂, LTB₄, and RvD1) in the peritoneum. Furthermore, DGAT1 inhibition accelerated sepsis-related mortality, coinciding with elevated bacterial loads in the peritoneum and bloodstream at 6- and 24-h post-sepsis. Our results demonstrate that LDs are critical regulators of innate immunity infection resistance, contributing to both bacterial clearance and the coordination of a protective proinflammatory response during sepsis through mechanisms dependent on DGAT-1 and Type I IFN.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156389"},"PeriodicalIF":11.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091961","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":"Emerging role of E4BP4/NFIL3 in metabolic homeostasis","authors":"Shuman Ran ,&nbsp;Siqi Wang ,&nbsp;Qi Jin ,&nbsp;Genzheng Liu ,&nbsp;Xiaobin Xue ,&nbsp;Peng Qu ,&nbsp;Liang Peng ,&nbsp;Hua Meng","doi":"10.1016/j.metabol.2025.156390","DOIUrl":"10.1016/j.metabol.2025.156390","url":null,"abstract":"<div><div>E4BP4/NFIL3 (E4 promoter-binding protein 4 or nuclear factor interleukin-3-regulated protein), is well-established for its association with circadian rhythm regulation and immune function. Recent advances in research have revealed its emerging and indispensable role in metabolic homeostasis, positioning it at the crossroads of circadian biology, immune responses, and metabolic balance. This review summarizes three decades of research on E4BP4/NFIL3 and explores its structural basis and regulatory functions. We synthesized current insights into the regulatory pathways that govern E4BP4/NFIL3 and discuss its central role in various metabolic scenarios, emphasizing its emerging significance as a pivotal metabolic regulator. Finally, we identify critical, unresolved questions and propose future research directions to enhance our understanding of E4BP4/NFIL3's broader implications in metabolic health.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"173 ","pages":"Article 156390"},"PeriodicalIF":11.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086404","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}