Journal of Endocrinology最新文献

{"title":"Non-enzymatic role of dipeptidyl peptidase-4 in regulating adenosine 2A receptor in MAFLD.","authors":"Yuli Cai, Xuan Niu, Ye Wang, Wei Liu, Qingwen Li, Jingjing Ma, Xiaolin Chen, Junfeng Li, Bo Yi, Zhongyuan Wen","doi":"10.1530/JOE-26-0029","DOIUrl":"https://doi.org/10.1530/JOE-26-0029","url":null,"abstract":"<p><p>Non-catalytic function of dipeptidyl peptidase-4 (DPP4) plays a crucial role in inflammation and immune regulation in the body; however, its significance in metabolic associated fatty liver disease (MAFLD) remains largely unknown. We sought to examine the effects of Dpp4 disruption on aspects of MAFLD and to elucidate underlying mechanisms. Wild-type (WT), Dpp4-disrupted, and DPP4 inhibitor-treated C57BL/6J male mice were fed a high-fat diet (HFD) for 12 weeks to establish MAFLD. Hepatic steatosis and liver proinflammatory responses were assessed. Furthermore, bone marrow-derived macrophages from different genotypes were co-cultured with mouse hepatocytes to assess their roles in inflammatory and metabolic responses in vitro. Upon HFD feeding, Dpp4-disrupted mice exhibited significantly attenuated hepatic steatosis and inflammation compared to both DPP4 inhibitor-treated and control WT mice. In vitro, Dpp4-deficient macrophages demonstrated a reduced proinflammatory phenotype. Consequently, these macrophages elicited less fat deposition in co-cultured wild-type hepatocytes. Mechanistically, Dpp4 deficiency significantly upregulated the protein abundance of the adenosine 2A receptor (A2AR) while markedly reducing adenosine deaminase (ADA) levels in both liver tissues and bone marrow-derived macrophages. Our results demonstrate that genetic disruption of Dpp4, unlike its pharmacological inhibition, ameliorates MAFLD progression. This protective effect is mediated through a novel non-catalytic mechanism involving the upregulation of A2AR and downregulation of ADA, which collectively inhibit macrophage-driven inflammation.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244946","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":"In memory of David J Mangelsdorf: my scientific interactions with Davo.","authors":"Wen Xie","doi":"10.1530/JOE-26-0222","DOIUrl":"https://doi.org/10.1530/JOE-26-0222","url":null,"abstract":"<p><p>David J Mangelsdorf was a senior colleague in the field of nuclear receptors who passed away unexpectedly in 2025. Dr Mangelsdorf and I share the same postdoctoral mentor at the Salk Institute. This article reflects on my scientific interaction with Dr Mangelsdorf, including the details of our research collaborations and how his discovery and early characterization of retinoid X receptor (RXR) and liver X receptor (LXR) receptor positively influence the research in my laboratory and many other laboratories in the nuclear receptor field.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194607","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":"miR-1236 regulates osteogenic and adipogenic differentiation by targeting BMP3 in osteoporotic fracture.","authors":"Hongling Yan, Jing Wang, Yanan Xiao, Jinju Pang, Xiao Chang, Na Zhu","doi":"10.1530/JOE-26-0228","DOIUrl":"https://doi.org/10.1530/JOE-26-0228","url":null,"abstract":"<p><strong>Background: </strong>Osteoporotic fracture (OPF) has become a major global public health issue. We aim to investigate the serum expression and fracture risk association of miR-1236 in OPF and its mechanisms in bone metabolism.</p><p><strong>Methods: </strong>This study included 83 osteoporosis (OP) patients and 93 OPF patients. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze gene expression levels. Lipofectamine 2000 was used to overexpress or inhibit miR-1236 in hFOB 1.19 human osteoblast cells and human bone marrow-derived mesenchymal stem cells (hBMSCs). Osteogenic differentiation was induced in hFOB 1.19 cells and adipogenic differentiation in hBMSCs. BMP3 was predicted as a target of miR-1236 by TargetScan and validated by dual-luciferase reporter assay. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to assess cell proliferation and apoptosis.</p><p><strong>Results: </strong>Serum miR-1236 was down-regulated in OPF patients. OPF patients presented elevated serum bone-metabolic markers (β-CTX, P1NP and BMP-3). miR-1236 was correlated with these bone-related markers in OPF patients. In hFOB 1.19 cells, miR-1236 promoted osteogenic differentiation. BMP3 was negatively regulated by miR-1236 and exerted an inhibitory effect on osteogenic differentiation. In hBMSCs, miR-1236 suppressed adipogenic differentiation, whereas BMP3 promoted adipogenic differentiation.</p><p><strong>Conclusion: </strong>Serum miR-1236 is decreased in patients with OPF, and is correlated with altered bone-metabolic markers. In-vitro findings demonstrate that miR-1236 promotes osteogenic differentiation and inhibits adipogenic differentiation by targeting BMP3.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182225","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":"A nuclear ERK-ATF5 axis coordinates mitochondrial metabolism and thermogenic gene expression in brown adipocytes.","authors":"Hyo Ju Jang, Yeongjun Suh, Jingwen Tian, Ho Yeop Lee, Ji Sun Moon, Ha Thi Nga, Thi Linh Nguyen, Alfin Mohammad Abdillah, Gyu Min Lim, Dong Wook Choi, Chuna Kim, Yonghoon Kwon, Hyon-Seung Yi","doi":"10.1530/JOE-26-0101","DOIUrl":"10.1530/JOE-26-0101","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Obesity and diabetes arise from disrupted energy homeostasis, underscoring the need to identify mechanisms that enhance energy expenditure. Brown adipose tissue dissipates energy through mitochondria-dependent non-shivering thermogenesis; however, the transcriptional regulators coordinating this process remain incompletely defined. Here, we investigated the role of activating transcription factor 5 in thermogenic programming and mitochondrial metabolism in brown adipocytes using in vivo and in vitro models. Cold exposure and β3-adrenergic stimulation induced activating transcription factor 5 expression in brown adipose tissue and differentiated adipocytes, accompanied by activation of thermogenic gene programs. Mechanistically, activating transcription factor 5 functioned downstream of a nuclear protein kinase A-extracellular signal-regulated kinase pathway, whose nuclear activation was required for its induction and for upregulation of uncoupling protein 1. Loss of activating transcription factor 5 impaired thermogenic gene expression, reduced mitochondrial stress response and lipolytic programs, diminished mitochondrial oxidative capacity, and suppressed fatty acid oxidation, including reduced incorporation of fatty acid-derived carbons into the tricarboxylic acid cycle. Transcriptomic analysis revealed coordinated repression of pathways related to fatty acid oxidation, oxidative phosphorylation, and thermogenesis in activating transcription factor 5-deficient adipocytes. Live-cell imaging further confirmed that β3-adrenergic stimulation selectively enhanced nuclear kinase activity, establishing a nuclear-localized signaling axis. Together, these findings identify activating transcription factor 5 as a key transcriptional regulator linking mitochondrial metabolism and thermogenic gene expression, supporting its potential as a therapeutic target for enhancing energy expenditure in metabolic disease.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137074","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":"TSPO deficiency uncovers a novel role for porphyrins in adipocyte lipid metabolism.","authors":"Carmen R Smith, Lan N Tu, Prasanthi P Koganti, Vimal Selvaraj","doi":"10.1530/JOE-25-0187","DOIUrl":"10.1530/JOE-25-0187","url":null,"abstract":"<p><p>The translocator protein (TSPO) is a mitochondrial outer membrane protein enriched in lipid-metabolic tissues, including white adipose tissue (WAT), but its physiological role in adipocytes remains poorly defined. Building on prior work that demonstrated a role for TSPO in mitochondrial fatty acid oxidation, we investigated whether TSPO contributes to adipocyte lipid homeostasis under metabolic stress. We employed a combination of in vivo and in vitro approaches using global Tspo knockout (Tspo-/-) mice, primary adipocyte cultures, and pharmacological TSPO-binding drugs to examine TSPO function. Our findings show that Tspo-/- mice exhibited increased gonadal and inguinal WAT mass and adipocyte hypertrophy following high-fat diet feeding in both sexes, with a modest late body weight increase in females, but no differences in feed intake. These changes were accompanied by suppression of key lipolytic genes, reduced circulating NEFA and glycerol levels, and altered expression of fatty acid oxidation genes. Lipidomic profiling showed no genotype-dependent changes, indicating impaired mobilization rather than altered lipid composition. In vitro, primary adipocytes derived from inguinal WAT of Tspo-/- mice exhibited enhanced lipid accumulation during differentiation and reduced expression of lipolytic genes. TSPO-binding drugs phenocopied this response in TSPO-expressing cells. Mechanistically, we identify protoporphyrin IX (PPIX), an endogenous TSPO ligand, as a suppressor of adipogenic and lipolytic programs. PPIX levels increase during adipogenesis, and its accrual inhibits both lipid accumulation and lipolytic programs. Our findings identify TSPO as a regulator of adipocyte lipid metabolism through a previously unrecognized TSPO-PPIX axis that influences lipid mobilization. This mechanism provides new insight into TSPO's role in adipose metabolic adaptation.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080940","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":"Inflammation-induced NFκB activation drives a pro-inflammatory and anti-apoptotic transcriptome in mouse islets.","authors":"Alicia White, Mack Solar, Kenneth L Jones, Natarajan Balasubramaniyan, Paul J Rozance, Clyde J Wright","doi":"10.1530/JOE-26-0138","DOIUrl":"10.1530/JOE-26-0138","url":null,"abstract":"<p><p>Diabetes results from an inflammatory insult to the pancreas. NFκB is a key transcription factor regulating cellular inflammatory responses. Therefore, we hypothesized that inflammatory exposures would acutely activate NFκB in the adult mouse pancreas and in isolated islets, leading to upregulation of target genes associated with inflammation and apoptosis. Mice were exposed to lipopolysaccharide (LPS), and isolated islets were exposed to a cytokine mixture to model a strong pro-inflammatory challenge. NFκB activation was determined by phosphorylation and nuclear translocation of NFκB proteins p65 and p50, dynamics of the inhibitors, IκBα and IκBβ, and the expression of NFκB target genes. NFκB target gene transcription was then correlated with p65 binding at promoter regions. Targeted apoptotic transcriptome changes were also evaluated. Systemic LPS exposure induced pancreatic NFκB activation, as evidenced by IκB oscillations and nuclear translocation of NFκB subunits. In isolated islets, cytokines triggered rapid p65 phosphorylation and DNA binding and increased NFκB target gene expression, with corresponding increases in specific promoter binding. Notably, anti-apoptotic genes were upregulated. These findings demonstrate that acute inflammatory stress activates NFκB in pancreatic tissue and islets, promoting a pro-inflammatory yet anti-apoptotic transcriptional response. Targeting NFκB at specific time points after inflammation may help prevent β-cell injury and diabetes development.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137132","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":"The evolutionary dynamics and functional refinement of IGF bioavailability in the vertebrate phylum: focus on IGFBPs.","authors":"Sophie Fouchécourt, Isabelle Callebaut, Philippe Monget","doi":"10.1530/JOE-26-0169","DOIUrl":"10.1530/JOE-26-0169","url":null,"abstract":"<p><strong>Abstract: </strong>In eutherians, insulin-like growth factor-1 (IGF-1) and IGF-2 exert insulin-like activity by interacting with type 1 receptor. IGF bioavailability is finely regulated by six IGF-binding proteins (IGFBPs), IGFBP-1 to IGFBP-6, which bind IGF-1 and IGF-2 with high affinity but not insulin. Moreover, the pregnancy-associated plasma protein-A (PAPP-A) protease is able to specifically degrade IGFBP-2, IGFBP-4, and IGFBP-5. In the present work, we were interested in the evolution of this regulation of bioavailability in vertebrates, in particular in the question of the different nodes of appearance of IGFs, IGFBPs, and PAPP-A in the tree of life. We confirmed that insulin-like/IGF peptides and their receptors appeared in non-vertebrate species, whereas IGFBPs first appeared in the vertebrate ancestor. More precisely, the first IGFBP that appeared was IGFBP-5 in amphioxus, whereas IGFBP-1, IGFBP-2, and IGFBP-3 appeared in lamprey, IGFBP-4 appeared in jawed fishes, and IGFBP-6 appeared in teleost, with the latter being lost in birds. We also showed that the PAPP-A and PAPP-A2 metzincin proteases, which degrade several IGFBPs, might have appeared in non-vertebrates and that their two inhibitors, proMBP and STC, probably appeared before both proteases. Interestingly, the cleavage sites of IGFBP were restricted to some species: for IGFBP-2 and IGFBP-5, they were present in mammals, birds, and reptiles, but not in amphibians and fishes, and for IGFBP-4, they were present in mammals only. Another important point is that another insulin-like peptide-binding protein found in the fruit fly, IMPL2, has probably disappeared in vertebrates.</p><p><strong>Highlights: </strong></p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016868","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":"Learning from Davo: a trainee's reflection on scientific generosity and mentorship.","authors":"Shengyi Sun","doi":"10.1530/JOE-26-0291","DOIUrl":"10.1530/JOE-26-0291","url":null,"abstract":"<p><p>David J 'Davo' Mangelsdorf is widely recognized for pioneering discoveries that transformed our understanding of nuclear receptor biology and endocrine physiology. Equally important, though less often described, was his extraordinary generosity as a mentor, collaborator, and scientific leader. This commentary reflects on his profound influence on my scientific development during my postdoctoral training at the University of Texas Southwestern Medical Center. As the scientific community reflects on Davo's remarkable career following his untimely passing in 2025, this personal perspective honors a legacy defined not only by his scientific discoveries, but also by the generations of scientists he inspired and empowered.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137123","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":"Pineal melatonin modulates responsiveness to exogenous melatonin via the IFN-γ-CXCL9/10-CXCR3 axis in gastric cancer.","authors":"Xiurong Wang, Chenyi Lin, Yuyang Zhang, Linxuan Wei, Yu Zhu, Rixiong Wang, Ruixiang Zhou, Hui Liu","doi":"10.1530/JOE-26-0238","DOIUrl":"10.1530/JOE-26-0238","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Melatonin is a pineal-derived neuroendocrine hormone with pleiotropic actions on tumor biology and immune regulation. Although exogenous melatonin has been reported to exert antitumor and immunomodulatory effects, whether these actions depend on an intact endogenous pineal melatonin background remains unclear. In particular, the role of endogenous melatonin in conditioning chemokine-mediated antitumor effects has not been defined. A male mouse gastric cancer model was used to investigate the interplay between endogenous and exogenous melatonin in tumor growth, immune infiltration, and chemokine signaling. Tumor and immune tissues were analyzed by flow cytometry, immunofluorescence, RT-qPCR, and western blotting. In vitro assays evaluated the direct effects of melatonin on chemokine expression in gastric cancer cells. Exogenous melatonin suppressed tumor growth in vivo and inhibited tumor cell proliferation in vitro. These effects were accompanied by increased intratumoral CD8+ T-cell accumulation and activation of the IFN-γ-CXCL9/10-CXCR3 axis within tumor tissues. Pinealectomy alone did not significantly alter baseline tumor progression, but it attenuated the tumor and chemokine responses to exogenous melatonin and disturbed splenic immune homeostasis. In gastric cancer cells, melatonin directly induced CXCL9 and CXCL10 expression, indicating that tumor cells contribute to endocrine-responsive chemokine amplification. Endogenous pineal melatonin contributes to optimal responsiveness to exogenous melatonin in this gastric cancer model. It provides a critical endocrine context for effective chemokine-mediated immune modulation by exogenous melatonin. By enhancing intratumoral immune cell recruitment while preserving immune homeostasis, melatonin integrates neuroendocrine and immune regulation to suppress tumor growth.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137128","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":"Iron deficiency impaired StAR-mediated steroidogenesis.","authors":"Xin-Yuan Cui, Lin-Qiang Ma, Jin-Bo Hu, Shuang-Shuang Zhu, Miao-Yun Chen, Yi-Fan He, Qing-Lian Zeng, Chuan Peng, Yong Xu, Wei Huang, Yun-Jie Xiong, Ru-Fei Gao, Qi-Fu Li, Shu-Min Yang, Yue Wang","doi":"10.1530/JOE-26-0235","DOIUrl":"10.1530/JOE-26-0235","url":null,"abstract":"<p><p>Iron deficiency (ID) impairs adrenocortical function, yet its underlying mechanism remains unclear. Here, we demonstrate that ID suppresses steroidogenic acute regulatory protein (StAR)-mediated adrenocortical steroidogenesis. In dietary ID mice, deferoxamine-treated mice, and H295R cells, mineralocorticoid and glucocorticoid hormone production was significantly reduced. Transcriptomic analysis revealed that ID-induced suppression of steroidogenesis was primarily associated with StAR downregulation, which was reversed by iron supplementation. Mechanistically, ID activated the ERK signaling pathway, leading to reduced StAR expression. Pharmacological inhibition of ERK restored both StAR protein levels and steroidogenic output. Collectively, our findings suggest that the ERK-StAR axis represents a potential regulatory pathway associated with ID-induced adrenocortical hypofunction.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137081","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}