Journal of Endocrinology最新文献

Vitamin D Receptor Agonist Calcipotriol Protects Against Alcohol-Induced Hepatotoxicity in Male Mice. 维生素D受体激动剂钙三醇对雄性小鼠酒精性肝毒性的保护作用。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-09-03 DOI: 10.1530/JOE-26-0192

Ambuj Shahi, Abhishek Yadav, Rohit A Sinha, Mable M Singh, Pratik Medhe, Rukhsana Mahamood, Anuj Kumar, Ashish Gupta

{"title":"Vitamin D Receptor Agonist Calcipotriol Protects Against Alcohol-Induced Hepatotoxicity in Male Mice.","authors":"Ambuj Shahi, Abhishek Yadav, Rohit A Sinha, Mable M Singh, Pratik Medhe, Rukhsana Mahamood, Anuj Kumar, Ashish Gupta","doi":"10.1530/JOE-26-0192","DOIUrl":"https://doi.org/10.1530/JOE-26-0192","url":null,"abstract":"Vitamin D deficiency is highly prevalent in alcohol-associated liver disease and may contribute to metabolic and inflammatory dysregulation in alcoholic steatohepatitis (ASH). To examine the hepato-metabolic actions of vitamin D receptor (VDR) activation in ASH, we evaluated calcipotriol, a VDR agonist, in male C57BL/6N mice fed a 5% ethanol-containing Lieber-DeCarli diet. Calcipotriol (20 µg/kg) reduced intra-hepatic triglyceride accumulation and serum alanine aminotransferase activity, indicating attenuation of alcohol-induced liver injury. Integrated transcriptomic, metabolomic, and biochemical analyses showed that VDR agonism suppressed hepatic lipogenic programs, including de novo lipogenesis, and improved alcohol-induced metabolic derangements. Calcipotriol also reduced oxidative injury and endoplasmic reticulum stress, as evidenced by lower hepatic protein carbonyl content and reduced p-eIF2α, XBP1s, CHOP, ATF4, and BiP expression, together with diminished inflammasome-associated inflammatory signalling. Metabolomic profiling further showed partial restoration of hepatic metabolic homeostasis by calcipotriol, as evidenced by increased choline, uridine monophosphate, and taurine levels. These findings identify calcipotriol as an endocrine-metabolic modulator of ASH and support VDR activation as a mechanistically relevant therapeutic strategy for alcohol-induced liver injury.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887473","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

Adropin in polycystic ovarian syndrome: expression and impact on human granulosa cell function. Adropin在多囊卵巢综合征中的表达及对人颗粒细胞功能的影响。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-09-01 DOI: 10.1530/JOE-25-0240

Patrycja Kurowska, Monika Dawid, Natalia Respekta-Długosz, Julia Oprocha, Oliwia Szkraba, Marek Skrzypski, Noémie Couty, Christelle Ramé, Fabrice Guérif, Jakub Wyroba, Joanna Kochan, Lechosław Gajda, Monika Trzcińska, Joelle Dupont, Agnieszka Rak

{"title":"Adropin in polycystic ovarian syndrome: expression and impact on human granulosa cell function.","authors":"Patrycja Kurowska, Monika Dawid, Natalia Respekta-Długosz, Julia Oprocha, Oliwia Szkraba, Marek Skrzypski, Noémie Couty, Christelle Ramé, Fabrice Guérif, Jakub Wyroba, Joanna Kochan, Lechosław Gajda, Monika Trzcińska, Joelle Dupont, Agnieszka Rak","doi":"10.1530/JOE-25-0240","DOIUrl":"10.1530/JOE-25-0240","url":null,"abstract":"Graphical abstract: Abstract: Adropin is a novel protein that regulates energy homeostasis. Serum and follicular fluid (FF) levels of adropin are decreased in women with polycystic ovarian syndrome (PCOS); however, its role in ovarian function remains unknown. The aims of this study were to determine the expression of adropin and its receptor G protein-coupled receptor 19 (GPR19), in human granulosa cells (GC), its immunolocalization, and its in vitro effects on GC function. Blood plasma, FF, and GC samples were obtained from normal-weight, obese, and women diagnosed with or without PCOS (n = 8). The in vitro effects of adropin on GC proliferation, apoptosis, cell cycle progression, and steroidogenesis were analyzed. The results revealed that adropin plasma concentration was decreased in obese patients, with a similar reduction observed in obese patients with PCOS, whereas GPR19 expression was decreased in the GC of obese and PCOS women, as well as in obese patients with PCOS. We noted that in all investigated patient groups, adropin reduced GC proliferation and cell cycle progression, negatively influenced steroidogenic enzyme levels, and promoted apoptosis. Such disruptions in GC function are likely to impair ovarian follicular maturation and contribute to the subfertility commonly observed in PCOS. These alterations may ultimately affect oocyte competence and ovarian responsiveness, parameters that are clinically relevant for in vitro fertilization outcomes. Our findings suggest that adropin may act as a novel regulator of ovarian function and could contribute to the pathophysiology of PCOS, highlighting its potential clinical value as a marker of altered ovarian follicular function in affected women.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766303","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

Empagliflozin improves gut microbial disturbances and intestinal barrier integrity in STZ-induced type 2 diabetic mice. 恩格列净改善stz诱导的2型糖尿病小鼠肠道微生物紊乱和肠道屏障完整性。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-09-01 DOI: 10.1530/JOE-26-0110

Ying Chang, Yuanjiang Zhou, Fanlin Zhou, Jie Liang, Gangyi Yang, Peng Zhang, Mingyuan Tian

{"title":"Empagliflozin improves gut microbial disturbances and intestinal barrier integrity in STZ-induced type 2 diabetic mice.","authors":"Ying Chang, Yuanjiang Zhou, Fanlin Zhou, Jie Liang, Gangyi Yang, Peng Zhang, Mingyuan Tian","doi":"10.1530/JOE-26-0110","DOIUrl":"10.1530/JOE-26-0110","url":null,"abstract":"Intestinal barrier dysfunction and gut microbiota dysbiosis contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). However, the effects of empagliflozin on the gut microbiota-intestinal barrier axis remain incompletely understood. This study investigated whether empagliflozin improves intestinal barrier integrity and gut microbiota profiles in a streptozotocin (STZ)-induced murine model of T2DM. Male C57BL/6 mice were fed a high-fat diet followed by STZ injection to induce T2DM and then treated with empagliflozin (10 mg/kg/day) for 8 weeks. Intestinal barrier-related proteins were assessed by immunofluorescence and western blotting. Gut microbial profiles were analyzed using 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), and inflammatory cytokines were quantified by GC-MS and ELISA. Empagliflozin treatment significantly reduced fasting blood glucose levels and attenuated weight gain in diabetic mice. Diabetic animals exhibited compromised intestinal barrier structure, accompanied by decreased tight junction protein expression (Claudin-1 and ZO-1) and enhanced TLR4/MyD88/NF-κB signaling, which were substantially alleviated following empagliflozin treatment. Concurrently, elevated inflammatory cytokines (IL-1β, IL-6, and TNF-α) and LPS levels were significantly reduced following empagliflozin treatment. Microbiome analyses revealed treatment-associated reorganization of gut microbial communities, including altered β-diversity patterns, shifts in diabetes-related taxa, and modified microbial interaction networks. In addition, empagliflozin increased fecal concentrations of key SCFAs, particularly butyrate and isohexanoate. Empagliflozin was associated with improved metabolic parameters, enhanced intestinal barrier integrity, reduced inflammation, and alterations in gut microbiota composition and predicted metabolic activity. Modulation of gut homeostasis may contribute to the therapeutic benefits of empagliflozin in T2DM.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793991","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

Dual roles of renal tubular mitochondrial Akt1 in protecting against diabetic nephropathy and improving body glucose metabolism. 肾小管线粒体Akt1在预防糖尿病肾病和改善机体葡萄糖代谢中的双重作用。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-25 DOI: 10.1530/JOE-26-0143

Esam S B Salem, Albert Ta, Elizabeth Bloom-Saldana, Patrick T Fueger, Ping H Wang

{"title":"Dual roles of renal tubular mitochondrial Akt1 in protecting against diabetic nephropathy and improving body glucose metabolism.","authors":"Esam S B Salem, Albert Ta, Elizabeth Bloom-Saldana, Patrick T Fueger, Ping H Wang","doi":"10.1530/JOE-26-0143","DOIUrl":"https://doi.org/10.1530/JOE-26-0143","url":null,"abstract":"Background: Diabetic nephropathy (DN) is a leading cause of chronic kidney failure. We hypothesized that mitochondrial Akt1 dysfunction in renal proximal tubules plays a pathogenic role in DN development and that its activation may reverse DN progression.Methods: To study this signaling pathway, we generated a transgenic mouse model harboring a renal tubule-specific, Tamoxifen-inducible, mitochondria-targeted constitutively active Akt1 (KMCAKT). Type 2 diabetes was induced by a high-fat, high fructose diet (HFFD) for 40 weeks. Renal histology and function were evaluated, and glucose metabolism was assessed using dynamic glucose testing.Results: HFFD feeding resulted in development of DN in control non-induced KMCAKT mice, whereas KMCAKT mice with constitutively active mitochondrial Akt1, induced by Tamoxifen-injection (TAM), exhibited significant improvement of kidney dysfunction and histology. Urinary albumin, fasting plasma BUN levels, fibrosis and Jablonski scores were all markedly improved in HFFD-TAM-KMCAKT mice compared with controls, while levels of α-smooth muscle actin (αSMA) and transforming growth factor-β1 (TGFβ1) were significantly reduced. HFFD-TAM-KMCAKT mice exhibited lower fasting blood glucose and improved oral glucose tolerance, while basal and stimulated insulin levels were higher, along with increased beta cell mass and insulin secretion (HOMA-β) compared to controls. Hyperglycemic clamp studies confirmed increased insulin secretion in HFFD-TAM-KMCAKT mice.Conclusion: Tubular mitochondrial Akt1 plays a key role in DN progression. Restoring tubular mitochondrial Akt1 signaling may represent a novel approach to reverse development of chronic kidney disease. We also identified previously unrecognized metabolic crosstalk between renal tubular mitochondrial Akt1 and pancreatic insulin secretion that may modulate systemic glucose homeostasis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817319","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

Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues. 确定矿皮质激素受体在肌肉骨骼健康和与其他组织的骨串扰中的潜在作用。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-24 DOI: 10.1530/JOE-24-0212

Husam Bensreti, Joseph C Shaver, Christopher L Yearwood, Dima W Alhamad, Eric C Morey, Shabiha Sultana, Mark W Hamrick, Kate Kosmac, Wendy B Bollag, Eric J Belin de Chantemele, Carlos M Isales, Meghan E McGee-Lawrence

{"title":"Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues.","authors":"Husam Bensreti, Joseph C Shaver, Christopher L Yearwood, Dima W Alhamad, Eric C Morey, Shabiha Sultana, Mark W Hamrick, Kate Kosmac, Wendy B Bollag, Eric J Belin de Chantemele, Carlos M Isales, Meghan E McGee-Lawrence","doi":"10.1530/JOE-24-0212","DOIUrl":"10.1530/JOE-24-0212","url":null,"abstract":"Excessive mineralocorticoid receptor (MR) activation in the heart and vasculature leads to pathological effects such as extracellular matrix accumulation, oxidative stress, and sustained inflammation. While MR's role in cardiovascular and renal systems is well understood, MR signaling has also been implicated as a key driver of homeostasis and pathological changes in several other body systems including skeletal muscle and adipose tissue. The glucocorticoid receptor (GR) and MR are structurally and functionally linked, sharing 95% similarity in DNA binding domains and recognizing many of the same hormone response elements (HRE) as transcriptional regulators of target genes. The role of GR in bone has been defined through several mechanistic studies, whereas the role of MR in bone is understudied. Because mineralocorticoid signaling regulates renal sodium and calcium handling, chronic hyperaldosteronism may indirectly disrupt skeletal homeostasis through urinary calcium wasting and secondary alterations in parathyroid hormone signaling. Furthermore, MR inhibition through MR antagonists (MRAs) has been associated with beneficial skeletal effects, particularly in settings of hyperaldosteronism and 11β-HSD2 deficiency. In this review, we present historical and current scientific findings on the role of genomic MR signaling in bone and extra-skeletal tissues that may be involved in crosstalk with the skeletal system. Furthermore, we also highlight the availability of tools to study MR signaling in the context of the musculoskeletal system.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813155","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

Scutellarin ameliorates PCOS in a mouse model by restoring mitochondrial function and inhibiting granulosa cell apoptosis. 黄芩苷通过恢复线粒体功能和抑制颗粒细胞凋亡改善PCOS小鼠模型。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JOE-25-0429

Zhi Li, Xiaoping Yang, Weifen Deng, Yudong Liu, Peixuan Lan, Yibo Song, Yanqiu Xie, Yuhua Shi

{"title":"Scutellarin ameliorates PCOS in a mouse model by restoring mitochondrial function and inhibiting granulosa cell apoptosis.","authors":"Zhi Li, Xiaoping Yang, Weifen Deng, Yudong Liu, Peixuan Lan, Yibo Song, Yanqiu Xie, Yuhua Shi","doi":"10.1530/JOE-25-0429","DOIUrl":"10.1530/JOE-25-0429","url":null,"abstract":"Polycystic ovary syndrome (PCOS), a common endocrine-metabolic disorder, lacks effective therapeutic options. Granulosa cell (GC) apoptosis and mitochondrial dysfunction are critical drivers of ovarian dysfunction in PCOS, yet targeted therapies are scarce. Scutellarin, a bioactive flavonoid, is a promising but unexplored candidate for treating PCOS. We investigated scutellarin's effects in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model and in DHEA-treated human granulosa-like KGN cells. We assessed metabolic and reproductive parameters, ovarian histology, and fertility and examined molecular mechanisms using transcriptomics, qRT-PCR, and western blotting. Apoptosis and mitochondrial function were evaluated via TUNEL staining, flow cytometry, and real-time mitochondrial assays. We found that scutellarin treatment was associated with improved metabolic phenotypes in PCOS mice, including glucose intolerance and insulin resistance, a normalized estrous cycle, lower serum testosterone and luteinizing hormone levels, better ovarian morphology, and enhanced fertility. Mechanistically, scutellarin correlated with reduced ovarian GC apoptosis and modulation of BCL2, BAX, and cleaved caspase-3. Transcriptomic analysis identified the PI3K/Akt signaling pathway as a key mediator, and scutellarin dampened its abnormal activation in DHEA-induced PCOS in vivo and in vitro. Furthermore, scutellarin was associated with improved mitochondrial function in DHEA-treated KGN cells, evidenced by reduced ROS production and restored membrane potential. We conclude that scutellarin is associated with the amelioration of metabolic and reproductive abnormalities in a PCOS mouse model, correlating with reduced GC apoptosis and improved mitochondrial function. By modulating these cellular defects, scutellarin offers potential dual benefits on ovarian and systemic dysfunctions, highlighting its value for clinical investigation and providing novel mechanistic insights.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664082","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

Renal Vdr deletion drives urinary calcium loss with intestinal and skeletal compensatory responses. 肾Vdr缺失导致尿钙流失，伴有肠道和骨骼代偿反应。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JOE-26-0151

Lieve Verlinden, Stefanie Doms, Iris Janssens, Kayleigh Rillaerts, Geert Carmeliet, Brigitte Decallonne, Annemieke Verstuyf

{"title":"Renal Vdr deletion drives urinary calcium loss with intestinal and skeletal compensatory responses.","authors":"Lieve Verlinden, Stefanie Doms, Iris Janssens, Kayleigh Rillaerts, Geert Carmeliet, Brigitte Decallonne, Annemieke Verstuyf","doi":"10.1530/JOE-26-0151","DOIUrl":"10.1530/JOE-26-0151","url":null,"abstract":"1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are endocrine regulators of calcium homeostasis. To assess the contribution of 1,25(OH)2D3-mediated renal calcium reabsorption to systemic calcium balance and bone homeostasis, we generated mice with a targeted deletion of the vitamin D receptor (VDR) in renal tubules (VdrRen- mice), weaned them onto diets containing 1% or 0.2% calcium, and examined their phenotype at 8 weeks of age. Despite higher urinary calcium excretion, VdrRen- mice maintained normocalcemia, suggesting compensatory adaptations in the intestine and bone. Transcript levels of intestinal calcium transporters were higher in male VdrRen- mice, particularly under dietary calcium restriction, whereas genotype-dependent changes were minimal in females. Bone mass was lower in VdrRen- mice of both sexes than in diet-matched wild-type littermates. On the 1% calcium diet, changes in calcium absorption and bone remodeling occurred without alterations in serum PTH and 1,25(OH)2D3, while FGF23 was elevated. Calcium restriction increased circulating PTH, 1,25(OH)2D3, and FGF23, with additional genotype- and sex-dependent effects on 1,25(OH)2D3 and FGF23. Together, these findings demonstrate that renal VDR signaling contributes to serum calcium conservation, and its loss triggers sexually dimorphic compensatory mechanisms in intestinal calcium absorption, especially under conditions of dietary calcium restriction.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520602","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

Rapamycin-induced fatty liver in mice is attenuated by chloroquine co-treatment in an ERRα-dependent manner. 氯喹以erα依赖的方式联合治疗雷帕霉素诱导的小鼠脂肪肝。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JOE-26-0176

Wafa B'chir, Catherine R Dufour, Sylvia Andrzejewski, Julie St-Pierre, Charlotte Scholtes, Vincent Giguère

{"title":"Rapamycin-induced fatty liver in mice is attenuated by chloroquine co-treatment in an ERRα-dependent manner.","authors":"Wafa B'chir, Catherine R Dufour, Sylvia Andrzejewski, Julie St-Pierre, Charlotte Scholtes, Vincent Giguère","doi":"10.1530/JOE-26-0176","DOIUrl":"10.1530/JOE-26-0176","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), remains a major health concern worldwide. Hepatic steatosis manifests by the aberrant accumulation of lipids in hepatocytes. We have previously shown that pharmacological inhibition of mTOR complex 1 (mTORC1) by rapamycin, a widely utilized potent immunosuppressant, induces MASLD under normal conditions. Notably, this phenotype was found exacerbated in mice with genetic or pharmacological inhibition of the master transcriptional regulator of energy metabolism, nuclear receptor ERRα. In this study, we show that combining antimalarial drug chloroquine with rapamycin attenuates the severity of hepatic lipid deposition observed with rapamycin monotherapy. Bulk mRNA-seq profiling showed that chloroquine co-injection reverses the upregulation of a large proportion of genes linked to lipid metabolism homeostasis found induced by rapamycin alone. Interrogation of these genes for direct transcriptional regulators identified ERRα among top candidates. Using a mouse model with genetic ERRα ablation, we demonstrate a crucial dependency on ERRα activity for the observed amelioration of rapamycin-induced hepatic steatosis by chloroquine addition. In ERRα-null liver, chloroquine failed to reverse and, in some instances, aggravated the upregulation of lipid metabolism genes by rapamycin, with evidence linking the impaired management of hepatic lipid overload to the underlying mitochondrial dysfunction. Together, these findings underscore a critical role of ERRα in reversing MASLD.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664077","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

Attenuation of diet-induced obesity and impaired glucose homeostasis by the IL-2/anti-IL-2 complex and hyperbaric oxygen. IL-2/抗IL-2复合物和高压氧对饮食性肥胖和葡萄糖稳态受损的抑制作用。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JOE-25-0474

Eun-Jeong Choi, Hyung-Ran Kim, Jeong-Hae Kie, Ju-Young Seoh, Joo-Ho Lee

{"title":"Attenuation of diet-induced obesity and impaired glucose homeostasis by the IL-2/anti-IL-2 complex and hyperbaric oxygen.","authors":"Eun-Jeong Choi, Hyung-Ran Kim, Jeong-Hae Kie, Ju-Young Seoh, Joo-Ho Lee","doi":"10.1530/JOE-25-0474","DOIUrl":"10.1530/JOE-25-0474","url":null,"abstract":"Obesity is characterized by chronic inflammation and impaired glucose homeostasis. Regulatory T cells (Tregs) preserve immunometabolic balance, and their reduction contributes to metabolic disturbances. Although IL-2/anti-IL-2 complex (IL-2C) and hyperbaric oxygen (HBO) therapy expand Tregs, their combined effects on obesity remain unclear. Male C57BL/6 mice were fed a low-fat diet (LFD) or a high-fat diet (HFD) for 16 weeks and treated with IL-2C and/or HBO. Both interventions significantly reduced HFD-induced body weight (9-22%, P < 0.05) independent of caloric intake, with no significant changes in LFD groups. Glucose tolerance and insulin sensitivity improved, showing significant reductions in IPGTT and IPITT area-under-the-curve values (20-25% and 30-35%, respectively; P < 0.05) compared with the HFD control. Combination therapy produced the most consistent metabolic improvements. Histological analysis demonstrated reduced adipocyte hypertrophy and crown-like structures in epididymal adipose tissue (P < 0.05). Treatments restored CD4+FoxP3+ Tregs, suppressed pro-inflammatory M1 macrophages, and decreased hypoxia-inducible factor-1α expression (P < 0.05). Consistent with these findings, histological examination revealed tissue-specific structural remodeling, characterized by restored multilocular adipocytes in iBAT and reduced adipocyte hypertrophy in iWAT under HFD conditions. These findings suggest that IL-2C and HBO improve immunometabolic dysfunction associated with obesity, in parallel with favorable adipose tissue remodeling and metabolic adaptation. Thus, IL-2C and HBO may represent complementary therapeutic strategies for enhancing metabolic health.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679002","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

The vitamin D receptor story: discovery, control, and genomic reach. 维生素D受体的故事：发现、控制和基因组覆盖。

IF 5.7 3区医学

Journal of Endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JOE-26-0204

Mark B Meyer, J Wesley Pike

{"title":"The vitamin D receptor story: discovery, control, and genomic reach.","authors":"Mark B Meyer, J Wesley Pike","doi":"10.1530/JOE-26-0204","DOIUrl":"10.1530/JOE-26-0204","url":null,"abstract":"The vitamin D receptor (VDR) is a ligand-activated nuclear receptor that mediates the biological actions of vitamin D and is a critical regulator of mineral homeostasis, cellular differentiation, immune function, and metabolism. VDR is a high-affinity intracellular binding protein for the most active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D). Early biochemical and molecular studies established VDR as a member of the nuclear receptor superfamily, functioning as a transcription factor that heterodimerizes with the retinoid X receptor and binds vitamin D response elements to regulate gene expression. Since the cloning of the VDR gene in the 1980s, characterization of its structural domains and identification of coregulators significantly advanced understanding of its genomic mechanisms of action. Over the past several decades, research has expanded the scope of VDR biology beyond classical calcium and phosphate metabolism. Genome-wide binding analyses and transcriptomic studies have revealed extensive VDR cistromes and context-dependent gene networks across diverse tissues. These advances have positioned VDR as a key factor linking vitamin D availability to tissue-specific outcomes. Despite substantial progress, fundamental questions remain, including mechanisms governing tissue-specific VDR actions, integration of genomic signaling pathways, and the role of VDR in complex diseases, such as cancer, autoimmune disorders, and aging. In addition, how VDR function is modulated by chromatin context, metabolic state, and the microbiome remains incompletely understood. Here, we summarize what is known about these actions of VDR and its history of discovery. Addressing these questions will be essential for translating mechanistic insights into improved therapeutic strategies targeting the vitamin D axis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678979","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}

引用次数: 0