Endocrine最新文献

{"title":"Incomplete male puberty: a new nosographic entity.","authors":"Sandro La Vignera, Rosita A Condorelli","doi":"10.1007/s12020-026-04732-2","DOIUrl":"10.1007/s12020-026-04732-2","url":null,"abstract":"<p><strong>Purpose: </strong>Incomplete male puberty is a recently proposed nosographic entity defined by the development of normal secondary sexual characteristics in boys who nonetheless fail to achieve adequate testicular volume (<12 mL) during puberty due to underlying Sertoli cell dysfunction. The condition typically goes unrecognised until the first spermiogram reveals azoospermia or severe oligozoospermia. This review examines the pathophysiology, available diagnostic tools, and clinical management strategies.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across SciSpace, PubMed, and Google Scholar covering Sertoli cell biology, AMH and Inhibin B as biomarkers, minipuberty physiology, endocrine disruptors, cryptorchidism, maternal metabolic disorders, and nutritional influences on testicular development. More than 500 relevant publications were retrieved and synthesised. This is a narrative review; no standardized or systematic methodology was applied for manuscript selection.</p><p><strong>Results: </strong>Minipuberty (months 1-6 of life) represents the earliest and most informative diagnostic window: Inhibin B peaks at 378 ± 23 pg/mL and AMH rises sharply, both reflecting Sertoli cell mass and function. Inhibin B below 60 pg/mL during this window predicts poor spermatogenic outcomes. Pubertal testicular volume progression below the P10 centile, or failure to reach ≥12 mL in adulthood, constitutes a cardinal sign. High-risk categories include cryptorchidism (bilateral Sertoli impairment in 70% of unilateral cases), offspring of diabetic or hypothyroid mothers, and boys exposed to endocrine-disrupting chemicals in utero.</p><p><strong>Conclusion: </strong>A structured surveillance protocol combining early infancy hormonal screening during minipuberty, serial orchidometry throughout childhood, and targeted Sertoli cell stimulation tests can identify incomplete male puberty years before irreversible spermatogenic failure. Early recognition enables timely intervention and counselling.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between candidate genes and FRAX scores in postmenopausal women.","authors":"Jessica Pepe, Arianna Viviani, Cristiana Cipriani, Bianca Maria Ciminelli, Carla Jodice, Luciano Colangelo, Marco Forti, Rachele Santori, Sara Terreri, Salvatore Minisola, Sara Latini, Marco Occhiuto, Patrizia Malaspina, Andrea Novelletto","doi":"10.1007/s12020-026-04739-9","DOIUrl":"10.1007/s12020-026-04739-9","url":null,"abstract":"<p><strong>Purpose: </strong>Single nucleotide polymorphisms (SNPs) have been associated with BMD and bone fracture risk. The aim of this study was to assess the possible association between FRAX scores and specific SNPs in Italian osteopenic and osteoporotic postmenopausal women.</p><p><strong>Methods: </strong>We enrolled 54 postmenopausal women with osteoporosis or osteopenia. FRAX (a computer-based free algorithm that provides the 10-year probability of fractures on the basis of classic risk factors) and BMD were obtained in every patient. We included 13 SNPs in the ESR1, OPG, RANK-L, VDR, PTH, CASR, COL1A1, CALCR, ACTN3 and TPRV6 candidate genes. We tested the association of principal component analysis scores based on individual multi-locus genotypes with FRAX.</p><p><strong>Results: </strong>A FRAX_M > = 20% was found in 20.3% and a FRAX_H > = 3% in 51.8% of patients. Twenty-four patients had a fragility fracture. At the level of single-locus associations, a significant difference (p = 0.046) was obtained for FRAX_H and the haplotype ESR1(GC), with mean values of 3.9 vs. 7.7 among non-carriers vs. carriers. In particular, patients characterized by high FRAX_M and FRAX_H values shared haplotype (GT) at PTH and allele G at OPG. On the opposite, patients in the low-risk FRAX score were characterized by COL1A1 allele A, CASR allele T, VDR haplotypes (GA) and (AA).</p><p><strong>Conclusion: </strong>In postmenopausal Italian women an appropriate combination of haplotypes/alleles at PTH and OPG genes is associated with high mean FRAX values. Long term studies would allow to assess if combining multi-locus genetic analyses with FRAX scores could empower physicians to tailor personalized preventive early strategies for osteoporosis.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the immune landscape of parathyroid carcinoma: implications for immunotherapeutic responsiveness.","authors":"Saransh Kanaujia, Md Ali Osama, Jayati Sarangi, Saumitra Dey Choudhury, Riyaz Ahmad Mir, Kamal Kataria, Sonali Dixit, Millo Tabin, Shipra Agarwal","doi":"10.1007/s12020-026-04724-2","DOIUrl":"10.1007/s12020-026-04724-2","url":null,"abstract":"<p><strong>Background: </strong>Parathyroid carcinoma is a rare endocrine malignancy with limited therapeutic options. Immune checkpoint blockade targeting the PD-1/PD-L1 axis has transformed the management of several solid tumors; however, its role in parathyroid carcinoma remains largely unexplored. Given that the response to immunotherapy is influenced not only by PD-L1 expression but also by the tumor immune microenvironment (TIME), characterization of the immune landscape in parathyroid carcinoma may provide insights into its potential therapeutic vulnerability.</p><p><strong>Objective: </strong>To evaluate PD-L1 expression and comprehensively characterize the tumor immune microenvironment in parathyroid carcinoma, enabling identification of features predictive of immunotherapeutic responsiveness.</p><p><strong>Methods: </strong>Using immunohistochemistry and multiplex immunofluorescence, this ambispective study investigated parathyroid carcinoma, parathyroid adenoma, and normal parathyroid tissues for PD-L1 expression (clone SP263, Ventana), infiltrating immune cells, namely cytotoxic T lymphocytes (CTLs; CD3⁺CD8⁺), regulatory T cells (Tregs; CD4⁺CD25⁺FOXP3⁺), and monocytic myeloid-derived suppressor cells (MDSCs; CD11b⁺CD14⁺). Immune cell densities were quantified per mm², and the TIME was categorized into four types based on PD-L1 expression and the presence of CTLs: Type I (PD-L1⁺/CTL-rich, adaptive immune resistance), Type II (PD-L1⁻/CTL-poor, immune ignorance), Type III (PD-L1⁺/CTL-poor, intrinsic induction), and Type IV (PD-L1⁻/CTL-rich, immune tolerance).</p><p><strong>Results: </strong>While 30% of adenomas showed patchy PD-L1 positivity (Tumor proportion score, TPS 3-6%), all carcinomas and normal parathyroid tissues were PD-L1-negative (TPS < 1%). Among the immune cells, CTLs and MDSCs were more abundant in the TIME of parathyroid carcinomas than in adenomas and normal tissues. Tregs were rare or absent. Parathyroid carcinomas demonstrated immune-tolerant (Type IV) or immunologically ignorant (Type II) microenvironmental profiles.</p><p><strong>Conclusions: </strong>Parathyroid carcinomas predominantly exhibit a PD-L1-independent immune-tolerant microenvironment, rich in CTLs and MDSCs. The results predict a limited benefit from single-agent PD-1/PD-L1 blockade and the need for myeloid-targeting and immune-priming multimodal strategies.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698160","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":"Ultrasound-guided thermal ablation in patients affected by Graves' disease: a systematic review and meta-analysis.","authors":"Elisa Gatta, Riccardo Morandi, Claudio Casella, Roberto Negro, Mario Rotondi, Carlo Cappelli","doi":"10.1007/s12020-026-04740-2","DOIUrl":"10.1007/s12020-026-04740-2","url":null,"abstract":"<p><strong>Introduction: </strong>Ultrasound-guided thermal ablation (U-GTA) techniques, including radiofrequency ablation (RFA) and microwave ablation (MWA), have recently been proposed as minimally invasive alternatives to surgery or radioiodine (RAI) therapy for patients with Graves' disease (GD) who are unresponsive to antithyroid drugs. However, evidence supporting its effectiveness and safety remains limited.</p><p><strong>Methods: </strong>A PubMed/MEDLINE, Web of Science, and Scopus research updated until January 31, 2026, was performed. The review question was: What is the euthyroidism rate (outcome) one year after U-GTA (intervention) in Graves' disease (population)? Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the prevalence with corresponding 95% confidence intervals.</p><p><strong>Results: </strong>Four studies comprising 82 patients (88% female) were included in the analysis. Approximately 2.4% of patients required levothyroxine replacement after U-GTA. Thyroid volume significantly decreased following treatment, and baseline thyroid volume was identified as a predictor of relapse in one study. A transient increase in anti-TSH receptor antibodies was observed one month after U-GTA, followed by a subsequent decline. No worsening or new onset of Graves' orbitopathy was reported. Post-procedural adverse events occurred in 6.1% of patients and were transient. At 12 months, pooled euthyroidism rate was 67.0% (95% CI 54-78), with low heterogeneity (I² = 0%).</p><p><strong>Discussion: </strong>U-GTA appears to induce biochemical remission in approximately two-thirds of selected patients with persistent or relapsed GD, with a favourable short-term safety profile and preservation of thyroid function in most cases. However, remission rates remain lower than those typically reported for definitive surgical treatment, and current evidence is limited to small, non-randomized studies with relatively short follow-up. Larger prospective comparative trials with standardized protocols are required to define the role of U-GTA within current management strategies for GD.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious complications following thyroid needle procedures: an underrecognized clinical challenge.","authors":"Roberto Novizio, Pasquale Zenone, Lucrezia D'Amore, Gennaro Lupone, Francesco Scavuzzo, Vincenzo Novizio","doi":"10.1007/s12020-026-04747-9","DOIUrl":"10.1007/s12020-026-04747-9","url":null,"abstract":"<p><p>Ultrasound-guided thyroid needle procedures, including fine-needle aspiration (FNA), percutaneous ethanol injection (PEI), and thermal ablation, are widely regarded as safe and effective. Infectious complications are exceptionally rare and may be underrecognized because their presentation can overlap with expected post-procedural inflammatory reactions or aseptic nodule rupture. We performed a focused narrative review of reported infections following thyroid needle procedures, examining their clinical presentation, microbiological findings, risk factors, and management. Published cases indicate that infections may occur after FNA, PEI, and thermal ablation, with considerable heterogeneity in timing, clinical severity, microbiological findings, and therapeutic approach. Reported management strategies range from antibiotic therapy alone to image-guided drainage or surgery, and no standardized treatment pathway is currently available. Early recognition, careful clinical and ultrasound assessment, and management tailored to disease severity are essential to limit progression to abscess formation or local and systemic complications. Greater awareness of these uncommon events may facilitate timely diagnosis and reduce both adverse outcomes and unnecessary interventions.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698209","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":"Determinants of physicians' risk-benefit perceptions of adjuvant radioactive iodine for differentiated thyroid cancer.","authors":"Carlos Garcia-Regal, Jhonatan Quiñones-Silva, Alberto Martinez-Lorca, Noemi Brox-Torrecilla, Sandra Campos Mena, Teresa Alonso-Gordoa, Joaquín Gómez-Ramírez, Pablo Valderrabano","doi":"10.1007/s12020-026-04717-1","DOIUrl":"10.1007/s12020-026-04717-1","url":null,"abstract":"<p><strong>Purpose: </strong>Selective use of radioactive iodine is advocated in recent guidelines. We aimed to characterize clinical practice and factors associated with its prescription in low- or intermediate-risk differentiated thyroid cancer patients among Spanish physicians.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted in 2022 among Spanish physicians. The survey assessed preferences for radioactive iodine administration in different differentiated thyroid cancer clinical scenarios with excellent response to surgery.</p><p><strong>Results: </strong>Ninety-six responses were received. In low-risk differentiated thyroid cancer, radioactive iodine was most often used to facilitate follow-up (40%), or to reduce the risk of recurrence (23%). Activity of radioactive iodine was selected according to treatment intention by 96% of respondents; but more than 50% of low-risk differentiated thyroid cancer patients received radioactive iodine treatment in the clinical setting of 2/3 of the respondents; and 13% routinely recommend adjuvant activities in this setting. In intermediate-risk differentiated thyroid cancer, the main objective of radioactive iodine administration was to reduce the risk of recurrence (81-83%). Adjuvant radioactive iodine was perceived to be well or very well tolerated (96% of respondents); with a positive risk-benefit balance in patients with low-risk (50%) or intermediate-risk (90%) differentiated thyroid cancer. Factors influencing physicians' likelihood to recommend radioactive iodine included an overestimation of its benefits; and underestimation of its risks; and perceived increased risk with increasing tumor size, nodal involvement, BRAF V600E mutation, and follicular/oncocytic histology.</p><p><strong>Conclusions: </strong>This survey shows discrepancy between reported clinical practice and current consensus guidelines as well as variation in practice patterns in Spain regarding [¹³¹I]NaI treatment.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698158","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":"Association of the combined triglyceride-glucose and frailty index with chronic kidney disease: evidence from two national cohort studies.","authors":"Chao Cheng, Yaohui Jiang, Qiuping Luo, Feng Qin, Jiuhong Yuan","doi":"10.1007/s12020-026-04738-w","DOIUrl":"10.1007/s12020-026-04738-w","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the relationships between TyG-Frailty Index (TyGFI), a comprehensive indicator of the triglyceride-glucose (TyG) index and frailty index (FI), and the risk of chronic kidney disease (CKD).</p><p><strong>Methods: </strong>A total of 8721 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 9670 participants from the U.S. National Health and Nutrition Examination Survey (NHANES) were included for cross-sectional study; while 4102participants from CHARLS were included for longitudinal study. For longitudinal study, cumulative TyGFI (CumTyGFI) is calculated, and the participants were categorized into four clusters on the basis of the dynamic changes in the TyGFI through K-means clustering. Multivariable logistic regression models and cox proportional hazards models were applied to estimate associations with CKD, with adjustment for demographic, clinical, and lifestyle covariates. Restricted cubic spline (RCS) and subgroup analyses were used to explore dose-response relationships and interaction effects, respectively.</p><p><strong>Result: </strong>Higher TyGFI, older age, hypertension, diabetes, and dyslipidemia were associated with CKD. In fully adjusted models, the highest TyGFI quartile (CHARLS: OR 3.98, 95% CI 3.03-5.22; NHANES: OR 4.49, 95% CI 3.55-5.69), highest CumTyGFI quartile (HR 4.18, 95% CI 3.09-5.65), and \"increasing TyGFI alteration\" cluster (HR 3.56, 95% CI 2.69-4.71) all showed significant associations, with dose‑response trends confirmed by RCS.</p><p><strong>Conclusion: </strong>In two national datasets, higher TyGFI was associated with prevalent CKD in the cross-sectional analyses and with incident CKD in the longitudinal CHARLS analysis. TyGFI may serve as a compact epidemiological marker combining metabolic and frailty-related burden, although its predictive and clinical utility requires further validation.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698190","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":"Reconsidering CVRR-based sleep apnea screening in non-obese diabetes: evidence requirements for clinical translation.","authors":"Cui Pengyuan, Cai Chunhong","doi":"10.1007/s12020-026-04737-x","DOIUrl":"10.1007/s12020-026-04737-x","url":null,"abstract":"","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698156","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":"Functional causes of low testosterone predominate in contemporary Australian endocrine referral practice: a two centre experience across 5 years.","authors":"Aongus O'Brolchain, Kacie McAndrew, William Newman, Dylan Young, Dian Van Zyl, Randunu Dissanyake, Elahe Ebrahimi, Katherine Griffin","doi":"10.1007/s12020-026-04722-4","DOIUrl":"10.1007/s12020-026-04722-4","url":null,"abstract":"<p><strong>Background: </strong>The epidemiology and outpatient management of low testosterone in Australian tertiary care remain poorly characterised. Rising testosterone prescription rates and evolving guidelines underscore the need to delineate contemporary referral patterns, diagnostic adherence, and therapeutic practice.</p><p><strong>Methods: </strong>A retrospective review was undertaken of all new male patients assessed for low testosterone levels at Gold Coast University and Robina Hospitals between 2020 and 2024. Demographic, biochemical, and management data were extracted from the integrated electronic medical record. Continuous variables were analysed using the Kruskal-Wallis test, categorical variables using χ² or Fisher's exact test, and binary logistic regression identified predictors of testosterone replacement therapy (TRT) initiation and pituitary imaging.</p><p><strong>Results: </strong>Among 294 consecutive referrals, functional low testosterone (43%) exceeded all pathological diagnostic categories combined individually. Obesity affected 65% of patients and obstructive sleep apnoea 28%, the latter highest in functional low testosterone (48%; p < 0.001). Two-thirds of referrals included two early-morning testosterone samples, pituitary imaging was performed in one-quarter of patients, with clinically actionable abnormalities identified in 4% of imaged men. TRT was prescribed in 25% of men, less often in functional than pathological forms (23% vs. 45%; OR 0.37, 95% CI 0.22-0.62; p < 0.001). Most patients were discharged after a median of three visits and six months' follow-up. Functional low testosterone was associated with a high burden of cardiometabolic and psychological comorbidity. Across the entire cohort, 31% reported previous androgen exposure.</p><p><strong>Conclusions: </strong>Most men referred with low testosterone did not have structural hypothalamic-pituitary-testicular axis disease, supporting a clinical approach prioritising identification of metabolic and reversible contributors before testosterone therapy. Diagnostic completeness and adherence to guideline-recommended imaging vary, but testosterone prescribing generally aligns with current Endocrine Society of Australia (ESA) and Pharmaceutical Benefits Scheme (PBS) restrictions. These findings support the establishment of a dedicated andrology service integrating metabolic, reproductive, and psychological care to optimise assessment and outcomes in men with androgen deficiency.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voluntary exercise ameliorates obesity and related metabolic disorders by promoting browning of visceral adipose tissue.","authors":"Junzheng Yu, Mengshu Cao, Sainan Ma, Xiushan Fan, Liang Tang, Lijun Sun","doi":"10.1007/s12020-026-04730-4","DOIUrl":"10.1007/s12020-026-04730-4","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate whether voluntary exercise alleviates obesity-induced metabolic disorders by promoting visceral adipose tissue (VAT) browning and to explore its potential mechanisms.</p><p><strong>Methods: </strong>Thirty male C57BL/6J mice were fed a normal diet (ND) or high-fat diet (HFD) for 8 weeks. Obese HFD mice were then divided into sedentary (HFD) or voluntary wheel running (HFD + VWR) groups and switched to standard diet for 4 weeks. VWR mice had access to unlocked running wheels; HFD controls had locked wheels.</p><p><strong>Results: </strong>Voluntary exercise significantly reduced obesity-associated metabolic disturbances compared to HFD controls, including decreased body weight, fat mass, serum insulin, triglycerides (TG), total cholesterol (T-CHO), and hepatic lipid accumulation. Crucially, voluntary exercise enhanced VAT browning, evidenced by upregulated UCP1 and PPAR-γ protein expression, as well as increased mRNA levels of beige adipocyte-specific markers TMEM26 and CD137. Additionally, VWR significantly upregulated the protein expression of the exercise-responsive factor FGF21 in VAT. Mechanistically, the observed browning phenotype was accompanied by alterations in the PI3K/AKT/mTOR signaling axis, characterized by enhanced PI3K/AKT activity and reduced mTOR phosphorylation, though the causal relationship remains to be established.</p><p><strong>Conclusions: </strong>Voluntary exercise mitigates obesity and metabolic dysfunction, may be associated with the regulation of VAT browning, potentially involving the PI3K/AKT/mTOR signaling axis, thus enhancing insulin sensitivity and reducing lipid accumulation. Unlike forced exercise, it is low-stress and self-regulated, offering a mechanistic reference for understanding exercise-induced adipose remodeling.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664593","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}