Journal of Endocrinology最新文献

Single-Cell Analysis of Oxidative Phosphorylation Protein Expression in Pancreatic Islets in Type 2 Diabetes. 2型糖尿病胰岛氧化磷酸化蛋白表达的单细胞分析。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-08 DOI: 10.1530/JOE-25-0253

Alana Mullins, Xuefei Yu, Anna Smith, George Merces, James Am Shaw, Laura Greaves, Mark Walker, Catherine Arden

{"title":"Single-Cell Analysis of Oxidative Phosphorylation Protein Expression in Pancreatic Islets in Type 2 Diabetes.","authors":"Alana Mullins, Xuefei Yu, Anna Smith, George Merces, James Am Shaw, Laura Greaves, Mark Walker, Catherine Arden","doi":"10.1530/JOE-25-0253","DOIUrl":"https://doi.org/10.1530/JOE-25-0253","url":null,"abstract":"Mitochondrial dysfunction is a key feature of type 2 diabetes and is closely linked to ageing, a major risk factor for the disease. This study investigated islet cell composition and mitochondrial oxidative phosphorylation protein expression in pancreatic tissue from older donors (≥62 years) with and without type 2 diabetes, matched for age, sex, and BMI. Fixed human pancreatic tissue sections were immunolabelled for insulin, glucagon, NDUFB8 (complex I), MTCO1 (complex IV), and VDAC1 (a mitochondrial mass marker) to quantify islet composition and mitochondrial protein levels. A machine learning-based single-cell segmentation pipeline enabled high-resolution profiling of individual cell populations within islets. In type 2 diabetes, islets exhibited an increased alpha: beta cell ratio, altered spatial organisation with fewer beta-beta and more alpha-alpha interactions, and a significantly higher proportion of bi-hormonal cells co-expressing insulin and glucagon. Within beta cells, we observed significant changes in mitochondrial protein expression, including reduced complex I and elevated complex IV levels. Unsupervised clustering of mitochondrial expression patterns identified three distinct beta cell expression clusters. Donors with type 2 diabetes showed a marked shift in distribution of beta cells across clusters, with increased proportions of beta cells exhibiting low complex I and high complex IV expression. These results highlight significant alterations in islet architecture and mitochondrial protein expression associated with type 2 diabetes, providing new insights into the mechanisms underlying type 2 diabetes.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251372","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}

引用次数: 0

A TIMELESS link to dedifferentiation in thyroid cancer. 与甲状腺癌去分化的永恒联系。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-08 DOI: 10.1530/JOE-25-0136

Jie-Jen Lee, Yi-Chiung Hsu, Chi-Yu Kuo, Shih-Yuan Huang, Shao-Chiang Chang, Shih-Ping Cheng

{"title":"A TIMELESS link to dedifferentiation in thyroid cancer.","authors":"Jie-Jen Lee, Yi-Chiung Hsu, Chi-Yu Kuo, Shih-Yuan Huang, Shao-Chiang Chang, Shih-Ping Cheng","doi":"10.1530/JOE-25-0136","DOIUrl":"https://doi.org/10.1530/JOE-25-0136","url":null,"abstract":"TIMELESS is considered a molecular hinge linking circadian rhythms and the cell cycle. We recently identified TIMELESS as one of the upregulated core circadian clock genes during thyroid cancer dedifferentiation, but its expression and significance in thyroid cancer remain unclear. To address this, we assessed TIMELESS expression in thyroid neoplasms using bioinformatics analysis, immunoblotting, and immunohistochemistry. TIMELESS expression progressively increased from normal thyroid tissue to differentiated thyroid cancer and then to anaplastic thyroid cancer. Silencing TIMELESS expression in thyroid cancer cells reduced clonogenicity and spheroid formation, induced G2/M cell cycle arrest, and impeded xenograft growth in NOD SCID mice. In the Cancer Genome Atlas, TIMELESS expression was negatively correlated with recombination proficiency scores. Knocking down TIMELESS increased sensitivity to doxorubicin in thyroid cancer cells and upregulated the mRNA expression of NKX2-1 and SLC5A5. In conclusion, the overexpression of TIMELESS is associated with thyroid cancer dedifferentiation and may serve as a potential target for combination therapies.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251353","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}

引用次数: 0

In vivo effects of cadmium on signaling and secretion of pituitary gonadotrophs in male mice are time-dependent. 体内镉对雄性小鼠垂体促性腺激素分泌和信号转导的影响具有时间依赖性。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-07 Print Date: 2025-10-01 DOI: 10.1530/JOE-25-0161

Yorgui Santiago-Andres, Elizabeth Hernández Álvarez, Daniel Ochoa Gutierrez, Ofelia Morton Bermea, Tatiana Fiordelisio

{"title":"In vivo effects of cadmium on signaling and secretion of pituitary gonadotrophs in male mice are time-dependent.","authors":"Yorgui Santiago-Andres, Elizabeth Hernández Álvarez, Daniel Ochoa Gutierrez, Ofelia Morton Bermea, Tatiana Fiordelisio","doi":"10.1530/JOE-25-0161","DOIUrl":"10.1530/JOE-25-0161","url":null,"abstract":"Cadmium is a heavy metal found widely in the environment, originating from industrial emissions, mining activities, phosphate fertilizers, and cigarette smoke. It is an endocrine-disrupting chemical that mimics essential metals such as calcium and zinc, interfering with hormone signaling. Due to its long biological half-life, cadmium bioaccumulates in organisms, raising concerns about its long-term effects on endocrine and reproductive health. Cadmium's reproductive toxicity is well documented, with studies highlighting its impact on gonadotropin regulation and testicular function. However, its specific effects on calcium (Ca2+) signaling in gonadotrophs remain poorly understood. This study aims to determine whether cadmium disrupts Ca2+-dependent signaling mechanisms essential for gonadotropin secretion. To address this, we used an adult male mouse model to assess pituitary cadmium accumulation, gonadotroph responsiveness to GnRH, and alterations in Ca2+ mobilization patterns. Our results show that cadmium exposure leads to pituitary bioaccumulation, prolonged endocrine disruption, and gonadotroph hyperplasia. Initially, gonadotroph responsiveness to GnRH declines, but over time, altered Ca2+ oscillation patterns and increased gonadotropin secretion emerge. A transition from normal oscillatory Ca2+ signaling to biphasic responses was observed, along with sustained phospholipase C-β (PLCβ) activation, suggesting persistent intracellular signaling disruptions. In addition, cadmium exposure resulted in testicular atrophy, increased apoptosis, and reduced sperm count. Testosterone levels declined, while the gonadotroph population increased, highlighting an imbalance in endocrine regulation. These findings suggest that cadmium induces reproductive toxicity through a combination of direct testicular damage and disruption of gonadotroph calcium signaling and hormone secretion, leading to testicular dysfunction that is relevant to public health.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080897","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}

引用次数: 0

Lactobacillus johnsonii N6.2 Improves Glycemia, and Reduces Diabetes-induced Organ Injury in the db/db Mice Model. 约氏乳杆菌N6.2在db/db小鼠模型中改善血糖，减少糖尿病诱导的器官损伤

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-03 DOI: 10.1530/JOE-25-0184

Monica F Torrez Lamberti, Sharon Thompson, Natalie A Harrison, Christopher L Gardner, Danilo R da Silva, Leandro D Teixeira, Kanthi Kiran Kondepudi, Claudio F Gonzalez, Sasanka S Chukkapalli, Graciela L Lorca

{"title":"Lactobacillus johnsonii N6.2 Improves Glycemia, and Reduces Diabetes-induced Organ Injury in the db/db Mice Model.","authors":"Monica F Torrez Lamberti, Sharon Thompson, Natalie A Harrison, Christopher L Gardner, Danilo R da Silva, Leandro D Teixeira, Kanthi Kiran Kondepudi, Claudio F Gonzalez, Sasanka S Chukkapalli, Graciela L Lorca","doi":"10.1530/JOE-25-0184","DOIUrl":"https://doi.org/10.1530/JOE-25-0184","url":null,"abstract":"Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia as well as the associated comorbidities. Type 2 diabetes is also associated with dysfunction of liver, kidney and nervous system. In addition, an altered microbiota is frequently observed in subjects with Type 2 diabetes. In this study a db/db (diabetic) mouse model of Type 2 diabetes was used to elucidate the beneficial effects of the probiotic Lactobacillus johnsonii N6.2. To evaluate metabolic effects, we performed metabolomics on liver samples, and RNA-seq from liver and visceral adipose tissue, followed by qRT-PCR validation. Using L. johnsonii N6.2 extracellular vesicles we evaluated lipid accumulation in hepatocytes. Finally, the gut microbiome of db/db mice was profiled using 16S rRNA sequencing. We observed that administration of the probiotic improved glycemic levels and decreased diabetes scores, as well as Type 2 diabetes-associated injury to the pancreas, liver and kidneys. Liver metabolomic and transcriptome analyses identified biomarkers of L. johnsonii N6.2 activity, including modulation of the vitamin K pathway, upregulation of FGF21-, a key regulator of glucose and lipid metabolism, and alternations in selected circadian genes. This study elucidates the beneficial effects of L. johnsonii N6.2, against the common symptoms of type 2 diabetes, highlighting its potential as an adjuvant therapeutic agent.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212810","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}

引用次数: 0

Effects of a GLP-1 Receptor Polymorphism on Responses to Liraglutide. GLP-1受体多态性对利拉鲁肽应答的影响。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-03 DOI: 10.1530/JOE-25-0174

Mona Mashayekhi, Bilgunay Ilkin Safa, Hui Nian, Jessica K Devin, Jorge L Gamboa, Chang Yu, Rui Chen, Joshua A Beckman, John R Koethe, Heidi J Silver, Kevin Niswender, James M Luther, Nancy J Brown

{"title":"Effects of a GLP-1 Receptor Polymorphism on Responses to Liraglutide.","authors":"Mona Mashayekhi, Bilgunay Ilkin Safa, Hui Nian, Jessica K Devin, Jorge L Gamboa, Chang Yu, Rui Chen, Joshua A Beckman, John R Koethe, Heidi J Silver, Kevin Niswender, James M Luther, Nancy J Brown","doi":"10.1530/JOE-25-0174","DOIUrl":"https://doi.org/10.1530/JOE-25-0174","url":null,"abstract":"The rs6923761 (Gly168Ser) missense variant in the glucagon-like peptide-1 receptor (GLP-1R) has been associated with favorable anthropometric and metabolic parameters in individuals with obesity but decreased responsiveness to incretin-based therapies. Here we performed a pre-specified analysis of a randomized controlled trial in individuals with obesity and pre-diabetes comparing treatment with the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 inhibitor sitagliptin or hypocaloric diet, and evaluated the effects of the rs6923761 variant on outcomes. We found significantly greater weight loss to liraglutide with each copy of the variant allele present, indicating a gene dose effect. In addition, individuals with the variant allele exhibited a significant reduction in the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 after liraglutide treatment. There was no effect of genotype on fasting glucose after liraglutide treatment, yet individuals with the variant allele exhibited decreased responsiveness to liraglutide and hypocaloric diet in measurements of fasting insulin, C-peptide, glucagon, as well as in HOMA-IR. In conclusion, we found that the GLP-1R rs6923761 variant exerts a dual impact on liraglutide efficacy -- enhancing weight loss while diminishing metabolic benefits. The observed associations could be consistent with constitutive activation of the GLP-1R in the presence of this variant with reduced activation/signaling in response to pharmacologic agents, a pattern that has been observed with the rs10305492 variant in animal models. Future studies are needed to investigate the molecular mechanisms of associations with the rs6923761 variant.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212772","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}

引用次数: 0

Phenotypic variations in polycystic ovary syndrome: metabolic risks and emerging biomarkers. 多囊卵巢综合征的表型变异：代谢风险和新兴生物标志物。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-03 Print Date: 2025-10-01 DOI: 10.1530/JOE-25-0226

Yi-Cih Ma, Kim-Seng Law, Wen-Sheng Wang, Hsun-Ming Chang

{"title":"Phenotypic variations in polycystic ovary syndrome: metabolic risks and emerging biomarkers.","authors":"Yi-Cih Ma, Kim-Seng Law, Wen-Sheng Wang, Hsun-Ming Chang","doi":"10.1530/JOE-25-0226","DOIUrl":"10.1530/JOE-25-0226","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with diverse clinical manifestations and metabolic risks. The 2012 NIH phenotypic classification, based on the presence of hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovarian morphology (PCOM), has enabled more nuanced characterization of PCOS into four phenotypes (A-D). Phenotypes A and B, both hyperandrogenic and anovulatory, are consistently associated with the highest metabolic risk, including insulin resistance, dyslipidemia, and increased prevalence of metabolic syndrome. Phenotype C, though ovulatory, still exhibits metabolic abnormalities due to androgen excess. In contrast, phenotype D, lacking hyperandrogenism, generally shows the mildest hormonal and metabolic profiles. This review outlines the evolving diagnostic landscape of PCOS, including the potential use of anti-Müllerian hormone (AMH) as a surrogate marker for PCOM. It explores hormonal and metabolic biomarkers, such as total and free testosterone, SHBG, LH/FSH ratio, HOMA-IR, and lipid parameters, in phenotype differentiation. Furthermore, emerging adipokines (e.g., adiponectin, chemerin, and ZAG) and inflammatory markers (e.g., CRP, IL-6, and TNF-α) provide additional insight into the metabolic heterogeneity of PCOS beyond obesity. Genetic and genomic studies have identified over 19 susceptibility loci involved in gonadotropin regulation, steroidogenesis, and insulin signaling, with distinct gene clusters aligning with adiposity, insulin resistance, and reproductive traits. MicroRNA signatures also show potential as phenotype-specific biomarkers. Recognizing phenotype-specific variations in PCOS is critical for individualized risk assessment and therapeutic strategies. Future research should prioritize standardized diagnostic criteria and large, diverse cohorts to validate emerging biomarkers and improve long-term outcomes for women with PCOS.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085953","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}

引用次数: 0

PTEN regulation by miR-486-5p contributes to the amelioration of polycystic ovary syndrome. miR-486-5p调控PTEN有助于改善多囊卵巢综合征。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-01 DOI: 10.1530/JOE-25-0247

Juan Wang, Boran Yan, Yanqiu Ding, Jingyun Cao

{"title":"PTEN regulation by miR-486-5p contributes to the amelioration of polycystic ovary syndrome.","authors":"Juan Wang, Boran Yan, Yanqiu Ding, Jingyun Cao","doi":"10.1530/JOE-25-0247","DOIUrl":"10.1530/JOE-25-0247","url":null,"abstract":"This research intended to identify the genes related to PCOS (Polycystic ovary syndrome) and verify the regulatory function of miR-486-5p as well as its target PTEN in granulosa cells (GCs). RT-qPCR was used to detect the expression of miR-486-5p in the serum, follicular fluid (FF), and granulosa cells (GC) of PCOS patients and normal subjects. ROC curve analysis indicated strong diagnostic performance. Bioinformatic analysis via miRDB and ENCORI databases predicted PTEN as a potential target of miR-486-5p, this prediction was validated through dual-luciferase reporter gene assays. Meanwhile, a series of functional assays were performed. Cellular proliferation capacity was quantitatively assessed using the CCK8 assay while flow cytometry was implied to determine cell apoptosis ratio. The secretion of pro-inflammatory mediators was quantitatively measured employing an ELISA kit. miR-486-5p was found to be reduced in serum from patients, as well as in patient FF and GCs. The enhanced expression of miR-486-5p strengthened the proliferation of GC and suppressing apoptotic activity, while concurrently attenuating pro-inflammatory cytokine secretion. Conversely, miR-486-5p inhibitor yielded opposing effects. Further investigation revealed that PTEN functioned as a negative regulatory factor of miR-486-5p. The increase of miR-486-5p caused a significant down-regulation of PTEN mRNA expression. Forced expression of PTEN reversed the cellular effects induced by miR-486-5p, including the enhanced proliferation rate, suppressed apoptosis, and attenuated inflammatory response. miR-486-5p can inhibit cell apoptosis and secretion of inflammatory factors by negatively regulating the expression of target gene PTEN, suggesting that miR-486-5p may be a potential target for PCOS.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199590","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}

引用次数: 0

Developmental regulation of fetal mitochondrial respiratory function towards term: the role of glucocorticoid and thyroid hormones. 胎儿线粒体呼吸功能的发育调节：糖皮质激素和甲状腺激素的作用。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-10-01 DOI: 10.1530/JOE-25-0135

A L Fowden, K L Davies, E J Camm, A J Forhead, A J Murray

{"title":"Developmental regulation of fetal mitochondrial respiratory function towards term: the role of glucocorticoid and thyroid hormones.","authors":"A L Fowden, K L Davies, E J Camm, A J Forhead, A J Murray","doi":"10.1530/JOE-25-0135","DOIUrl":"10.1530/JOE-25-0135","url":null,"abstract":"Mitochondria are unique intracellular organelles that have their own DNA and are inherited intact in the oocyte. They have multiple functions, the most important of which is producing energy in the form of ATP by oxidative phosphorylation (OXPHOS) using a range of metabolic substrates. As energy requirements increase with intrauterine growth and the onset of new postnatal functions at birth, mitochondria develop structurally and functionally in utero to meet these energy demands. In part, the developmental and prepartum maturational changes in mitochondrial OXPHOS capacity depend on the endocrine environment and the natural rise in the fetal concentrations of hormones, such as cortisol and tri-iodothyronine (T3), towards term. This review discusses the development of mitochondrial respiratory function during late gestation with an emphasis on tissue OXPHOS capacity. It considers the role of cortisol and thyroid hormones, in particular, in the intrauterine development and prepartum maturation of mitochondrial OXPHOS capacity in preparation for extrauterine life. Finally, it briefly examines the potential longer-term consequences of abnormal hormonal exposure before birth on mitochondrial OXPHOS function later in postnatal life. Endocrine regulation of mitochondrial OXPHOS in the fetus is shown to be multifactorial, dynamic and tissue specific with a central role in determining functional development. It optimises energetics for survival both in utero and at birth and has implications for adult metabolic fitness and the inheritance of mitochondrial phenotype.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199606","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}

引用次数: 0

CL316,243 and skeletal muscle metabolism: role of sex and estrogen receptor beta. CL316,243与骨骼肌代谢：性别和雌激素受体β的作用。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-09-25 Print Date: 2025-09-01 DOI: 10.1530/JOE-25-0005

Alan Maloney, Jinseok Lee, Eric D Queathem, Kylie A Schaller, Shahad Buckhary, Dennis B Lubahn, Rudy J Valentine, Victoria J Vieira-Potter

{"title":"CL316,243 and skeletal muscle metabolism: role of sex and estrogen receptor beta.","authors":"Alan Maloney, Jinseok Lee, Eric D Queathem, Kylie A Schaller, Shahad Buckhary, Dennis B Lubahn, Rudy J Valentine, Victoria J Vieira-Potter","doi":"10.1530/JOE-25-0005","DOIUrl":"10.1530/JOE-25-0005","url":null,"abstract":"CL316,243 (CL), a beta 3 adrenergic receptor (B3-AR) agonist, has 'exercise mimetic' effects in adipose tissue. CL may also positively affect skeletal muscle (SM), yet the role of estrogen receptor beta (ERβ) in mediating SM-specific effects of CL is not known. We investigated the effects of CL on SM metabolism, as well as the role played by ERβ. High-fat diet-fed male and female wild-type (WT) and ERβ DBD knockout (KO) mice were administered CL daily for 2 weeks. Quadriceps SM protein markers of fatty acid oxidation (FatOx), protein synthesis, and protein catabolism were assessed. CL increased relative lean mass in both sexes (P = 0.012). In females, CL increased FatOx in WT, yet reduced FatOx in KO, while among males, CL reduced FatOx independent of genotype (P = 0.04). Uncoupling protein 2 (UCP2) and fatty acid synthase (FASN) abundance were higher in females (P = 0.004 and 0.037, respectively), and in both sexes, KO mice had higher SM UCP2 abundance (P = 0.022). CL increased phosphorylated acetyl-CoA carboxylase in males, yet reduced it in females (P = 0.015). Similarly, CL affected p706S kinase abundance (indicative of anabolic signaling) in a sexually dimorphic manner, increasing in males and decreasing in females. CL robustly increased SM FASN across sexes and genotypes (P < 0.001). In summary, the most salient finding was that CL increased SM FASN content independent of sex and ERβ genomic activity; additional novel sex-divergent effects of CL on SM metabolism were identified, some of which were affected by ERβ genomic activity.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029958","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}

引用次数: 0

Dysbiosis in the upper airway and gut, and altered urine metabolome in Malaysian diabetic patients. 马来西亚糖尿病患者上呼吸道和肠道的生态失调和尿液代谢组的改变。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-09-23 Print Date: 2025-09-01 DOI: 10.1530/JOE-25-0102

Chin-Lee Ting, Zhi-Xian Kong, Nur Alia Binti Johari, Cindy Shuan-Ju Teh, Ivan Kok-Seng Yap, David William Cleary, Stuart C Clarke, Victor Lim, Lokman Hakim Bin Sulaiman, Nurain Binti Mohd Noor, Zanariah Hussein, Chun-Wie Chong

{"title":"Dysbiosis in the upper airway and gut, and altered urine metabolome in Malaysian diabetic patients.","authors":"Chin-Lee Ting, Zhi-Xian Kong, Nur Alia Binti Johari, Cindy Shuan-Ju Teh, Ivan Kok-Seng Yap, David William Cleary, Stuart C Clarke, Victor Lim, Lokman Hakim Bin Sulaiman, Nurain Binti Mohd Noor, Zanariah Hussein, Chun-Wie Chong","doi":"10.1530/JOE-25-0102","DOIUrl":"10.1530/JOE-25-0102","url":null,"abstract":"Gut dysbiosis and an increased risk of respiratory infection in type 2 diabetes have been well recognised. However, the relationship between the gut and respiratory pathobiont carriage rates in the type 2 diabetic Malaysian population is understudied. To address the knowledge gap, we profiled the gut and upper respiratory tract (URT) microbial composition, and the urine metabolome of 31 type 2 diabetic adults and 14 non-diabetic adults. We showed a higher prevalence of opportunistic URT pathogens in diabetes patients. A higher abundance of pro-inflammatory bacteria Escherichia coli was detected in the gut of the diabetic subjects. This coincided with the higher levels of sorbitol and taurine in the urine. The former is produced by aldose reductase, an enzyme strongly associated with airway inflammation, while the latter is a substrate for bacterial antioxidants (i.e. H2S). Despite a small sample size, our study revealed the potential relationship between the carriage rates of URT pathobionts with the gut microbial and urine metabolomic profiles of diabetes patients.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015513","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}

引用次数: 0