Molecular and Cellular Endocrinology最新文献

{"title":"Aggressive pituitary tumours and pituitary carcinomas: molecular insights guiding management and the role of precision oncology","authors":"LS Lamb ,&nbsp;HW Sim ,&nbsp;SJ Ramus ,&nbsp;AI McCormack","doi":"10.1016/j.mce.2025.112598","DOIUrl":"10.1016/j.mce.2025.112598","url":null,"abstract":"<div><div>Aggressive pituitary neuroendocrine tumours and pituitary carcinomas are associated with high morbidity and mortality and have limited treatment options. Increased understanding of the molecular pathogenesis of pituitary tumours has led to identification of molecular drivers of aggressive behaviour and prognostic markers, as well as identification of therapeutic targets. Mechanisms for pituitary tumourigenesis include chromosomal genomic instability, defective DNA repair, loss of cell cycle control, epigenetic changes, dysregulation of intracellular signalling pathways and alterations within the pituitary tumour immune microenvironment. Novel therapeutic treatment options including VEGF targeted therapies and immune checkpoint inhibitors have been used with varied responses. The application of precision oncology platforms to identify therapeutic targets is well described in other cancers and should be considered in the management of aggressive pituitary tumours and pituitary carcinomas. Histopathological analysis of established prognostic markers should be included in routine clinical practice.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112598"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOC2L inhibits trophoblast ferroptosis in preeclampsia through the p53/SLC7A11 pathway","authors":"Fengyun Su ,&nbsp;Fanhua Shi ,&nbsp;Chun Yang ,&nbsp;Fei Zhao ,&nbsp;Xiaolin Geng ,&nbsp;Xiaojing Yang ,&nbsp;Xudong Zhao","doi":"10.1016/j.mce.2025.112589","DOIUrl":"10.1016/j.mce.2025.112589","url":null,"abstract":"<div><h3>Background</h3><div>NOC2L is downregulated in preeclampsia (PE). However, the underlying functional mechanisms of NOC2L in the pathogenesis of PE remain unclear.</div></div><div><h3>Methods</h3><div>Cell viability, migration, and invasion were determined in hypoxia-stimulated HTR-8/SVneo cells in CCK-8, wound healing, and Transwell assays. The levels of GSH, MDA and Fe²⁺ were measured using specific commercial kits. Lipid ROS levels were determined through C11-BODIPY staining. The protein levels were analyzed via western blotting. Additionally, a rat model of PE was used to examine the influence of NOC2L on the progression of PE and the associated ferroptosis.</div></div><div><h3>Results</h3><div>NOC2L overexpression increased the viability of hypoxia-treated trophoblast cells and increased the levels of GSH, SLC7A11, and GPX4 while simultaneously reducing Fe²⁺, MDA, and lipid ROS levels. Furthermore, both NOC2L overexpression and ferrostatin-1 application facilitated trophoblast migration and invasion. In contrast, NOC2L knockdown exacerbated the hypoxia-induced increase in ferroptosis and inhibited cell migratory and invasive capabilities. Notably, treatment with PFT-α, a p53 inhibitor, abolished the influence of NOC2L silencing on trophoblast cell functions. NOC2L overexpression was associated with improved blood pressure and urinary protein concentration, reduced pathological damage in the placenta, alterations in ferroptosis-related markers, and an increased survival rate in rat fetuses.</div></div><div><h3>Conclusion</h3><div>NOC2L inhibits trophoblast ferroptosis through the p53/SLC7A11 signaling pathway, potentially preventing the progression of PE.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112589"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ghrelin treatment and exercise improve sperm quality in rats fed an obesogenic diet:A potential link to LEAP2","authors":"E.M. Luque ,&nbsp;V.P. Carlini ,&nbsp;P. Guantay ,&nbsp;D. Machuca ,&nbsp;P. Torres ,&nbsp;N. Ramírez ,&nbsp;V. Cantarelli ,&nbsp;M. Ponzio ,&nbsp;D. Castrogiovanni ,&nbsp;M. Perelló ,&nbsp;A.C. Martini","doi":"10.1016/j.mce.2025.112608","DOIUrl":"10.1016/j.mce.2025.112608","url":null,"abstract":"<div><div>This study aimed to evaluate whether ghrelin, with or without exercise, can reverse the alterations caused by an obesogenic diet on sperm quality, metabolism, and endocrine profile with emphasis on LEAP2 levels.</div><div>Fifty five male Wistar rats were randomly assigned, from weaning to postnatal day (pnd) 103, to five groups (n = 11/group): CD (standard chow + water); ObD (chow enriched with 30 % pork fat + water with 5 % fructose); ObD + ghrelin (obesogenic diet + 6 nmol/animal/day of ghrelin from pnd 85); ObD + Exc (obesogenic diet + standardized exercise in a running wheel, 15 min/day, 3 days/week); and ObD + ghrelin + Exc.</div><div>Body weight gain was accelerated in ObD, but ghrelin and/or Exc slowed it down. At pnd 103, all treatment groups were significantly lighter than the ObD group. Metabolic parameters were impaired in ObD animals, with exercise markedly improving them, reducing cholesterol and triglyceride levels close to control values, while ghrelin exerted a modest effect, partially reducing triglycerides and the triglyceride/HDL index but leaving values still dysregulated. Sperm concentration and motility were significantly reduced in the ObD vs. CD; ghrelin and/or Exc completely reversed these detrimental effects. Plasma LEAP2 was significantly higher in the animals receiving the obesogenic diet, and, LEAP2 correlated inversely with sperm concentration, explaining 22 % of its variation. No synergistic effects were found between ghrelin and Exc.</div><div>We demonstrated for the first time the potential of ghrelin to reverse sperm quality alterations secondary to obesity. Furthermore, ghrelin exhibited weight gain-slowing effects comparable to those of Exc. We also found an association between LEAP2 and sperm concentration, which warrants further investigation.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112608"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Gut to Brain: The roles of intestinal microbiota, immune system, and hormones in intestinal physiology and gut–brain–axis","authors":"Muhammad Talha Khan ,&nbsp;Muhammad Zohair ,&nbsp;Areeba Khan ,&nbsp;Ahmed Kashif ,&nbsp;Sadia Mumtaz ,&nbsp;Fiza Muskan","doi":"10.1016/j.mce.2025.112599","DOIUrl":"10.1016/j.mce.2025.112599","url":null,"abstract":"<div><div>The intestine plays numerous roles in the normal physiology of our body. Gut-brain axis (GBA) is a complex communication network linking the gastrointestinal (GI) tract and central nervous system (CNS). This bidirectional system integrates endocrine, neural, and immune signals, impacting host metabolism and cognition. The gut microbiota, a critical component of the GBA, significantly impacts gut hormones, neurotransmission, neural development, and other components of gut-brain-axis. The microbiota-gut-brain axis facilitates communication via metabolites such as short chain fatty acids (SCFAs), and neurotransmitters such as dopamine, γ-amino butyric acid (GABA) and serotonin. The microbiota influences gut peptide production, including ghrelin, glucagon like pepetide-1 (GLP-1), serotonin, and cholecystokinin (CCK), thereby modulating nutrient absorption and immune responses. Gut hormones such as ghrelin, CCK, GLP-1, gastric inhibitory peptide (GIP), serotonin (5-HT), neurotensin, peptide YY (PYY) and melatonin play key roles in the GBA. These hormones play several roles including modulation of appetite and satiety, metabolism of nutrients such as lipid and glucose, insulin and glucagon secretion, and influence on gut inflammation, mood, learning and cognition. The interaction between gut microbiota and these hormones underscores their role in maintaining gut-brain homeostasis. Dysbiosis, or microbial imbalance, is linked to altered stress responses, anxiety, and depressive behaviors, highlighting the therapeutic potential of microbiota modulation. Despite the significant roles of gut hormones and microbiota in the GBA, literature on their cellular and molecular mechanisms is limited, and often based on animal models. This review synthesizes current understanding of hormones secreted by the intestine, their physiological effects and the cellular and molecular mechanisms of action underlying these effects, with a focus on their roles in the GBA. By elucidating these complex relationships, the review aims to advance research and clinical applications, offering insights into gastrointestinal and systemic health.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112599"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYR61 and CTGF mediate the stimulatory effect of amphiregulin on COX-2 expression in human granulosa-lutein cells","authors":"Bingxin Fu ,&nbsp;Manman Guo ,&nbsp;Yuanyuan Jia,&nbsp;Xiaoyu Han,&nbsp;Beibei Bi,&nbsp;Lanlan Fang,&nbsp;Jung-Chien Cheng","doi":"10.1016/j.mce.2025.112604","DOIUrl":"10.1016/j.mce.2025.112604","url":null,"abstract":"<div><div>Amphiregulin (AREG), an epidermal growth factor (EGF)-like ligand, is the predominant epidermal growth factor receptor (EGFR) ligand in human follicular fluid and mediates the effects of luteinizing hormone (LH) on ovarian function. In this study, we investigated whether AREG regulates the expression of cysteine-rich angiogenic inducer 61 (CYR61) and connective tissue growth factor (CTGF), two key matricellular proteins involved in ovarian function, and whether they mediate AREG-induced cyclooxygenase-2 (COX-2) expression. Using the human granulosa cell tumor-derived KGN cell line and primary human granulosa-lutein (hGL) cells, we demonstrated that AREG treatment upregulated CYR61 and CTGF protein levels in an EGFR-dependent manner. Mechanistic analysis revealed that AREG-induced expression of CYR61 and CTGF was mediated through the ERK1/2, AKT, CREB, and YAP signaling pathways. Inhibition of these pathways using specific inhibitors or small interfering RNA blocked AREG-induced CYR61 and CTGF expression, indicating their essential roles in this process. Moreover, knockdown of CYR61 and CTGF attenuated AREG-induced COX-2 expression, establishing their role as key mediators of AREG signaling in human granulosa cells. Finally, our results showed that LH treatment induced the expression of CYR61 and CTGF, and this induction was attenuated by EGFR inhibition. Moreover, knockdown of CYR61 and CTGF reduced LH-induced COX-2 expression. These findings provide novel insights into the molecular mechanisms by which AREG regulates ovarian function and highlight potential targets for reproductive health research.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112604"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteroendocrine cell differentiation: Implications for human disease","authors":"Elisa Saint-Denis ,&nbsp;Bianca Frintu ,&nbsp;Madelyn Goldsmith ,&nbsp;Guilherme P. Ramos ,&nbsp;Daniel Zeve","doi":"10.1016/j.mce.2025.112607","DOIUrl":"10.1016/j.mce.2025.112607","url":null,"abstract":"<div><div>Enteroendocrine cells are the most abundant hormone producing cells in humans. Though they make up less than 1 % of the gastrointestinal epithelium, these cells have a large physiological impact through the secretion of hormones that act both locally and systemically to regulate intestinal function and whole-body metabolism, among other functions. The differentiation of enteroendocrine cells from intestinal stem cells is complex, involving not only lineage, but hormonal specification. This review highlights the specific signaling pathways and transcription factors that regulate enteroendocrine cell differentiation and hormone production, integrating newer findings into our growing understanding of this process. Further, it also describes how enteroendocrine cells and their differentiation are involved and altered in human health and disease: specifically aging, inflammatory bowel disease, obesity, and diabetes mellitus. Finally, we focus on how enteroendocrine cells can be targeted to produce insulin, a growing field with significant implications. Understanding what drives enteroendocrine differentiation, both molecularly and physiologically, will provide important insights into how these cells can serve as future therapeutic targets.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112607"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcospan, a candidate gene of fat distribution, may affect lipid storage in adipocytes","authors":"Katharina Anastasia Dinter ,&nbsp;Samantha Aurich ,&nbsp;Luise Müller ,&nbsp;Adhideb Ghosh ,&nbsp;Falko Noé ,&nbsp;Christian Wolfrum ,&nbsp;Matthias Blüher ,&nbsp;Anne Hoffmann ,&nbsp;Peter Kovacs ,&nbsp;Maria Keller","doi":"10.1016/j.mce.2025.112602","DOIUrl":"10.1016/j.mce.2025.112602","url":null,"abstract":"<div><h3>Background and aims</h3><div>Genetic and epigenetic variations in the <em>Sarcospan</em> (<em>SSPN</em>) gene are associated with parameters of fat distribution (body mass index, waist-to-hip ratio), glucose homeostasis and adipocyte size in human potentially by affecting adipogenesis. This study aims at clarifying the impact of <em>SSPN</em> on adipogenesis, particularly focusing on its promoter methylation.</div></div><div><h3>Materials and methods</h3><div>Immortalized murine epididymal preadipocytes were transfected with fluorescence-marked plasmids coding for DNMT3a, CRISPR/dCas9-Suntag and vectors carrying guide RNAs complementary to the transcription start site region and differentiated to mature adipocytes. We performed siRNA-mediated <em>Sspn</em> knockdown in epididymal preadipocytes, measured target DNA methylation using pyrosequencing and quantified transcriptional changes of <em>Sspn</em> and adipogenic genes by qPCR. Additionally, we correlated <em>SSPN</em> mRNA values and clinical characteristics from a large human adipose tissue biobank (Leipzig Obesity Biobank).</div></div><div><h3>Results</h3><div>Epigenetic editing of the <em>Sspn</em> regulatory region in preadipocytes resulted in a significant increase (up to 35 %) in DNA promoter methylation throughout adipocyte differentiation but showed only minor effects on <em>Sspn</em> expression and fat storage. Though siRNA knockdown could also not contribute to understand the role of <em>Sspn</em> in a 2D adipogenesis model, large-scale correlation analyses still indicate the gene to be a key player in fat distribution and glucose homeostasis.</div></div><div><h3>Conclusions</h3><div>Although the epigenetic downregulation of <em>Sspn</em> showed only marginal effects on adipogenesis, associations of <em>SSPN</em> expression in human adipose tissue with parameters of fat distribution and glucose homeostasis make it a promising candidate for further studies addressing metabolic processes in adipose tissue.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112602"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SP600125 decreases cAMP/PKA-dependent steroid production through ATF4/DDIT3 activation in MA-10 Leydig cells","authors":"Audrey Basque ,&nbsp;Liel-Sarah Izichkis ,&nbsp;Luc J. Martin","doi":"10.1016/j.mce.2025.112613","DOIUrl":"10.1016/j.mce.2025.112613","url":null,"abstract":"<div><div>Leydig cells, located between seminiferous tubules within the testis, are the primary source of testosterone in males. In these cells, the luteinizing hormone (LH)/cAMP/protein kinase A (PKA) signaling pathway mainly regulates androgen biosynthesis. We have previously reported that the <em>connexin43</em> (<em>Gja</em>) promoter can be activated in mouse MA-10 Leydig cells as a result of a cooperation between the AP-1 transcription factors JUN and FOS. The mitogen-activated protein kinases (MAPK) signaling pathway, through the JUN N-terminal kinase (JNK), can phosphorylate members of the AP-1 family of transcription factors, modulating their activities. Hence, MA-10 Leydig cells were treated for 4 h with the JNK inhibitor SP600125 (pyrazolanthrone) at 25 μM, in the absence or presence of the activator of adenylate cyclase forskolin (FSK) at 10 μM, followed by RNA extractions and 3′Tag RNA-Seq analysis of the transcriptome. Interestingly, SP600125 decreases cAMP/PKA dependent expression of genes related to cholesterol and steroid biosynthetic/metabolic processes, resulting in decreased cAMP/PKA dependent progesterone production in MA-10 cells. Moreover, SP600125 increases the expression of genes involved in the endoplasmic reticulum stress response related to ATF4, resulting in activation of DDIT3 and apoptosis as indicated with cleaved caspase 3. Overall, our results suggest that SP600125 increases the ATF4/DDIT3-dependent endoplasmic reticulum stress response independently of MAPK9 (JNK2) inhibition, and inhibits LH/cAMP/PKA-dependent androgen synthesis in Leydig cells.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112613"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia” [Mol. Cell. Endocrinol. (2019), 498, 110576 (doi: 10.1016/j.mce.2019.110576)]","authors":"Vanessa M. Lima ,&nbsp;Caroline A. Lino ,&nbsp;Nathalia Senger ,&nbsp;Tábatha de Oliveira Silva ,&nbsp;Renata I.B. Fonseca ,&nbsp;Michael Bader ,&nbsp;Robson A.S. Santos ,&nbsp;Jose Donato Júnior ,&nbsp;Maria Luiza M. Barreto-Chaves ,&nbsp;Gabriela P. Diniz","doi":"10.1016/j.mce.2025.112590","DOIUrl":"10.1016/j.mce.2025.112590","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112590"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of glucose intake drives distinct hepatic outcomes: Divergent glucose and lipid metabolism","authors":"Xiaofu Zhang ,&nbsp;Chenfei Ma ,&nbsp;Shichen Chang ,&nbsp;Xiaoying Li ,&nbsp;Qiuyu Wang","doi":"10.1016/j.mce.2025.112611","DOIUrl":"10.1016/j.mce.2025.112611","url":null,"abstract":"<div><h3>Objective</h3><div>Excessive sugar intake is strongly associated with insulin resistance and type 2 diabetes (T2D), yet the metabolic consequences of nutrient timing—specifically glucose consumption during fasting versus feeding—remain poorly understood.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were subjected to an every-other-day fasting (EODF) regimen and randomly divided into three groups: control (tap water only), food-glucose (FG; glucose water during feeding), and starvation-glucose (SG; glucose water during fasting). After 22 weeks, metabolic phenotypes, hepatic lipid profiles, insulin signaling markers, and hepatic transcriptomes were analyzed.</div></div><div><h3>Results</h3><div>Glucose intake during fasting (SG) induced marked hepatic insulin resistance, as evidenced by reduced phosphorylation of Akt and FoxO1. In contrast, glucose intake during feeding (FG) promoted hepatic triglyceride accumulation, upregulated lipogenic genes (e.g., Acaca, Fasn), and increased expression of SREBP-1c and PPARγ. Transcriptomic and pathway enrichment analyses revealed distinct activation patterns of insulin signaling and lipid metabolism between FG and SG groups.</div></div><div><h3>Conclusions</h3><div>Nutrient timing critically influences hepatic metabolic responses: glucose intake during feeding promotes lipogenesis, whereas intake during fasting triggers insulin resistance. These findings underscore the importance of chrononutritional strategies in preventing T2D and suggest that personalized dietary timing may offer therapeutic benefits.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"607 ","pages":"Article 112611"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}