Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

{"title":"Reversing Dysfunction of CCR9⁺ Regulatory T Cells by Targeting the IL-21/IL-17 Axis Improves Type 1 Diabetes.","authors":"Yulian Xia, Qing He, Yuhui Yao, Lei Yang, Shanshan Zhan, Shunfeng Mao","doi":"10.2147/DMSO.S605204","DOIUrl":"10.2147/DMSO.S605204","url":null,"abstract":"<p><strong>Objective: </strong>The functional status of regulatory T cells expressing the gut-homing receptor CCR9 (CCR9⁺ Tregs) in type 1 diabetes mellitus (T1DM) remains unclear. This study aims to investigate the functional alterations of CCR9⁺ Tregs in a T1DM model and evaluate the interventional effect of targeting the IL-21/IL-17 axis on their dysfunction.</p><p><strong>Methods: </strong>The spontaneous T1DM non-obese diabetic (NOD) mouse model was employed. CCR9⁺ and CCR9^- Treg subsets were isolated from the spleen by flow cytometry. Their in vitro suppressive capacity on effector T cell (Teff) proliferation was assayed, and cytokine expression was analyzed using flow cytometry and qPCR. In vitro, CCR9⁺ Tregs were treated with different concentrations (50 and 100 ng/mL) of the anti-IL-21 monoclonal antibody (Avizakimab) to assess its effects on IL-21/IL-17A secretion and immunosuppressive function. In vivo, T1DM NOD mice were randomly assigned to a saline control group (n=3) and an Avizakimab treatment group (n=3, 10 mg/kg, tail vein injection, every other day for 2 weeks). Fasting blood glucose levels were monitored, pancreatic insulitis and pathological damage were evaluated by H&E staining, and the proportion of peripheral blood IL-17A⁺ cells was analyzed by flow cytometry.</p><p><strong>Results: </strong>Compared to CCR9^- Tregs, CCR9⁺ Tregs exhibited a significantly reduced ability to suppress Teff proliferation, secreted less of the anti-inflammatory cytokine IL-10, and showed significantly upregulated expression of the pro-inflammatory cytokines IL-17A and IL-21. Avizakimab effectively and dose-dependently inhibited the abnormal secretion of IL-21 and IL-17A by CCR9⁺ Tregs in vitro and restored their suppressive function on Teff proliferation. In vivo, Avizakimab treatment significantly lowered fasting blood glucose levels in T1DM NOD mice, alleviated pancreatic insulitis and pathological damage, and downregulated the proportion of IL-17A⁺ cells in peripheral blood.</p><p><strong>Conclusion: </strong>In the T1DM milieu, CCR9⁺ Tregs become dysfunctional and shift towards a pro-inflammatory phenotype, thereby exacerbating the autoimmune response. The anti-IL-21 monoclonal antibody Avizakimab can reverse the dysfunction of CCR9⁺ Tregs and ameliorate disease symptoms by inhibiting the IL-21/IL-17 axis, providing a novel potential strategy for the immunotherapy of T1DM and highlighting the translational potential of targeting this axis.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"605204"},"PeriodicalIF":3.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886662","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":"Wnt/β-Catenin Signaling in Diabetic Complications: Mechanisms and Therapeutic Potential.","authors":"Xuelian Liu, Yuefen Liu, Yun Zhang, Zhanqi Cao, Qie Guo, Hongyan Ji, Donghua Liu","doi":"10.2147/DMSO.S606697","DOIUrl":"10.2147/DMSO.S606697","url":null,"abstract":"<p><p>Diabetic complications, driven by chronic hyperglycemia and complex pathogenic mechanisms, are a major global health challenge, yet the basis of tissue-specific injury and repair remains unclear. Wnt/β-catenin signaling has emerged as an important regulator in these complications, but its role is highly context dependent, promoting pathological remodeling in some tissues while impairing repair in others. This review is distinguished by its integration of current evidence on the dual and often opposing roles of Wnt/β-catenin signaling across six major diabetic complications: diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic cutaneous ulcers (DCU), diabetic cardiomyopathy (DCM), diabetic neuropathy, and diabetic osteoporosis (DOP). We first outline the major pathological features and clinical significance of each complication, highlighting the recurring observation that hyperglycemia often causes aberrant activation of this pathway in DN, DR, and DCM, where it promotes epithelial-to-mesenchymal transition, extracellular matrix accumulation, fibrosis, inflammation, and pathological angiogenesis. In contrast, we then examine conditions in which Wnt/β-catenin signaling is suppressed, particularly in DCU, DOP, and certain forms or stages of DPN, leading to impaired wound healing, reduced bone formation, and defective nerve regeneration. We subsequently analyze the cell type- and stage-specific mechanisms underlying these divergent effects, including cross-talk with oxidative stress, the renin-angiotensin system, and transforming growth factor-β signaling. Following a detailed discussion of emerging therapeutic strategies, such as LRP6-targeting biologics, small-molecule modulators, and agents derived from traditional Chinese medicine, we summarize preclinical evidence showing that carefully tuned, context-specific modulation of Wnt/β-catenin can improve both pathological and functional outcomes. This review is intended to clarify the potential mechanisms linking Wnt/β-catenin signaling to diabetic complications and to guide the rational development of new therapies that take into account its tissue-specific and stage-specific effects.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"606697"},"PeriodicalIF":3.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864013","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":"HDAC9 in Insulin Resistance: An Update on Epigenetic Mechanisms, Inflammatory Crosstalk, and Therapeutic Potential.","authors":"Lingzhen Meng, Jing Liu, Zhihong Liu","doi":"10.2147/DMSO.S622182","DOIUrl":"10.2147/DMSO.S622182","url":null,"abstract":"<p><p>Insulin resistance is one of the main causes of type 2 diabetes mellitus and metabolic disorders. Histone deacetylase 9 (HDAC9) belongs to the class IIa histone deacetylase family. It remodels chromatin structure and modulates gene expression to regulate adipocyte differentiation, inflammatory responses, and hepatic glucose homeostasis, thereby inhibiting insulin signaling. However, the complete and precise molecular mechanisms underlying these processes remain unclear. This review systematically summarizes the molecular characteristics and regulatory mechanisms of HDAC9, and analyzes its biological functions under insulin resistance from the perspectives of chromatin remodeling and transcriptional regulation. This review further explores whether HDAC9 exacerbates insulin resistance through regulating adipocyte differentiation, mediating inflammatory responses and disrupting hepatic glucose metabolic homeostasis. Meanwhile, this review evaluates HDAC9-targeted therapeutic prospects for metabolic diseases and offer theoretical support for future precision interventions.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"622182"},"PeriodicalIF":3.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863978","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":"Younger Age is Associated with Treatment and Complication Outcomes Among Type 2 Diabetes Mellitus Patients in Kigali University Teaching Hospital.","authors":"Abdullateef Isiaka Alagbonsi, Aime P N Kagina, Denyse Ingabire, Moise Nayituriki, Alliance Tusifu, Hawau Olaide Abdulkadir, Aliyu O Olaniyi, Noah A Omeiza, Mojeed Akorede Gbadamosi","doi":"10.2147/DMSO.S614442","DOIUrl":"10.2147/DMSO.S614442","url":null,"abstract":"<p><strong>Aims: </strong>Current diabetes mellitus (DM) prevention and treatment strategies rely on risk factors adapted from developed countries, which may not be effective in most poor sub-Saharan Africa settings. This study investigated the association between diabetic treatment outcomes and complications with sociodemographic and diabetic risk factors among type 2 DM (T2DM) patients in Rwanda.</p><p><strong>Methods: </strong>This cross-sectional study analyzed the records of T2DM patients who accessed care at Kigali University Teaching Hospital (CHUK) between January and December 2020, using a non-random sampling technique. Treatment outcomes (improved or not improved based on glycemic control target) and complication outcomes (presence or absence of DM-related microvascular and macrovascular events) were the primary outcome variables. Data were analyzed using <i>t</i>-tests, chi-square tests, and multivariable analyses as appropriate.</p><p><strong>Results: </strong>After adjusting for confounders, only age remained significantly associated with treatment and complication outcomes. The adjusted prevalence ratio (PR) of treatment outcomes for patients aged <50 years was 1.43 (95% CI 1.07-1.92; p = 0.016) and for those aged 50-64 years was 1.12 (95% CI 0.83-1.52; p = 0.462), both relative to the ≥65 years reference category. The adjusted PR for complication outcomes was 0.59 (95% CI 0.40-0.86; p = 0.005) for patients aged <50 years and 0.72 (95% CI 0.57-0.91; p = 0.007) for those aged 50-64 years, compared with the ≥65 years reference category. The adjusted PRs for smoking, alcohol consumption, pharmacological therapy, non-pharmacological therapy, and diet were attenuated and no longer statistically significant (all p > 0.05).</p><p><strong>Conclusion: </strong>The outcomes of diabetic treatment in Rwanda are associated with the age of the patients, rather than the type of therapy or the assessed sociodemographic and risk factors. The causal interpretation and generalizability of this study are limited by its cross-sectional design, non-random sampling, and the single-center setting.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"614442"},"PeriodicalIF":3.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863992","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":"Methodological and Statistical Considerations Regarding the Assessment of Psychological Distress and Disordered Eating in Obesity: A Letter to the Editor.","authors":"Dandan Chi, Yuntao Guan","doi":"10.2147/DMSO.S639894","DOIUrl":"10.2147/DMSO.S639894","url":null,"abstract":"","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"639894"},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857131","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 of Serum Meteorin-Like with OCTA Metrics in Type 2 Diabetic Nonproliferative Retinopathy: A Cross-Sectional Study.","authors":"Xinyue Yu, Saijia Li, Zichun Wei, Yuqin Tang, Linjia Guo, Yingqi Liu, Kewei Wang, Qincheng Qiao, Xinguo Hou, Fei Yan","doi":"10.2147/DMSO.S556677","DOIUrl":"10.2147/DMSO.S556677","url":null,"abstract":"<p><strong>Purpose: </strong>Meteorin-like (Metrnl), a novel secreted myokine, has been implicated in metabolic imbalance and the pathogenesis of type 2 diabetes mellitus (T2DM). The present work sought to determine whether circulating Metrnl concentrations are associated with alterations in retinal microcirculation, assessed via optical coherence tomography angiography (OCTA), in individuals living with T2DM.</p><p><strong>Patients and methods: </strong>This cross-sectional investigation enrolled 160 adults with T2DM, including those with and without nonproliferative diabetic retinopathy (NPDR). Each participant underwent OCTA imaging, from which vessel density (VD), foveal avascular zone (FAZ) area, and ganglion cell complex (GCC) thickness were automatically extracted. Multivariable analytical models were constructed to evaluate independent associations between serum Metrnl levels and OCTA-derived microvascular metrics.</p><p><strong>Results: </strong>Totally, 160 eyes from 160 patients (median age: 56 years [IQR 48-64]; 64% male; median diabetes duration: 10 years [IQR 5-16]) were analyzed. Serum Metrnl concentrations were markedly reduced in DR patients relative to those without DR (425.59 ± 95.69 vs 479.02 ± 96.85 pg/mL, p = 0.002). Decreasing Metrnl concentrations were accompanied by a reduction in retinal VD. After adjustment for potential confounders, higher Metrnl levels remained significantly associated with greater VD in both the superficial vascular complex and deep vascular complex. No significant relationships were observed between Metrnl levels and FAZ area or GCC thickness.</p><p><strong>Conclusion: </strong>Serum Metrnl concentrations are positively associated with retinal microvascular perfusion in T2DM. Further studies are needed to explore whether Metrnl plays a role in the development or progression of DR.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"556677"},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812133","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":"Optimizing Nutrition Strategies for Diabetes Management in India: An Expert Opinion.","authors":"Banshi Saboo, Ameya Joshi, Subir Chandra Swar, Mahesh D M, Anantharaman Ramakrishnan, Apoorva Hajirnis, Suhas Khaire, Subrata Chakrabarti, Sreedevi Patnala, Sattik Siddhanta, Virendra A Patil, Parthasarathy Balasubramanian, Uthra Subash Chandra Bose, Sriram Kalangani Mohan, Nandan Arun Joshi, Sourabh Bharat Sonawale","doi":"10.2147/DMSO.S624092","DOIUrl":"10.2147/DMSO.S624092","url":null,"abstract":"<p><p>A distinct \"South Asian phenotype\" and unhealthy dietary patterns contribute to the high burden of type 2 diabetes mellitus (T2DM) in India, highlighting the need for context-specific nutritional management. Five regional advisory board meetings were conducted to gather expert perspectives on the unique epidemiology of T2DM and key aspects of nutritional management, including optimal dietary practices and the role of high-protein, high-fiber (HPHF) supplements or meal replacements. A total of 60 experts attended the meetings. During each meeting, an optional multiple-choice poll was administered as part of the discussion. Expert perspectives were derived from optional poll responses and discussions informed by scientific evidence and participants' clinical experience. High carbohydrate and low protein intake, insulin resistance, central obesity, suboptimal muscle mass, and genetic predisposition characterize Indian patients with diabetes. Recognizing this phenotype is essential for providing tailored nutritional interventions. Key assessments to facilitate nutritional interventions include anthropometry (weight, body mass index, and waist circumference), lipid profile, and 24-hour dietary recalls. Experts emphasized that customized nutrition plans should be developed based on individual nutritional status, clinical profile, and dietary preferences. Dietary strategies should emphasize increased consumption of complex carbohydrates, high-fiber foods, and protein. The high burden of \"diabesity\" underscores the need for nutritional interventions addressing both glycemic control and weight management, including the appropriate use of meal replacement strategies. Protein and fiber are key nutrients in diabetes management. While dietary sources should be prioritized, experts noted that low-glycemic index, HPHF supplements/replacements may be considered for patients with overweight/obesity, poor nutrition intake, weakness or fatigue, or uncontrolled hyperglycemia. However, their limited use in clinical practice highlights the need for further research to evaluate their indications for use, effectiveness, safety, implementation, cost considerations, and long-term outcomes. This expert opinion highlights the unique epidemiology of T2DM in India and provides context-specific, evidence-informed insights to support nutritional management strategies. These perspectives are derived from advisory board discussions and should be interpreted as expert opinion rather than systematic evidence synthesis or formal guideline recommendations.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"624092"},"PeriodicalIF":3.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789507","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":"Identification of Factors Associated with Glycemic Control Using the PRECEDE- PROCEED Model in Patients with Type 2 Diabetes: A Cross-Sectional Study.","authors":"Juan Tu, Guoxin Lin, Feng Zhu, Feipeng Xu, Yuan Gao, Qiulan Gan, Yali Chen, Xiaofang Hu, Rui Tang","doi":"10.2147/DMSO.S598614","DOIUrl":"https://doi.org/10.2147/DMSO.S598614","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify the predisposing, enabling, and reinforcing factors associated with glycemic control in patients with type 2 diabetes mellitus, and to provide preliminary evidence for developing continuity management programs across hospital and community settings.</p><p><strong>Methods: </strong>A cross-sectional survey design was used. Based on the PRECEDE-PROCEED planning model, 220 patients with type 2 diabetes were assessed using a general information questionnaire, the Chronic Disease Management Self-Efficacy Scale, the Type 2 Diabetes Self-Management Behavior Scale, and the Social Support Rating Scale. Data were analyzed using the chi-square test, Spearman correlation analysis, and multiple linear regression analysis.</p><p><strong>Results: </strong>The average age of patients with type 2 diabetes was 57.90 (SD=14.28), and the average course of disease was 8.76 (SD=7.52). Overall, 25% of patients achieved the glycemic control target of HbA1c < 7%. Age, disease duration, smoking history, self-efficacy, self-management behavior, and social support were significantly associated with HbA1c and jointly accounted for 44.4% of its variance.</p><p><strong>Conclusion: </strong>The rate of adequate glycemic control among patients with type 2 diabetes mellitus remains suboptimal. Within the PRECEDE-PROCEED framework, self-efficacy may represent a predisposing factor, self-management behaviors an enabling factor, and social support both an enabling and reinforcing factor affecting glycemic control. These findings indicate that future continuity management programs should integrate tailored interventions targeting self-efficacy enhancement, self-management behavior improvement, and social support reinforcement. The incorporation of intelligent terminal technologies may further support personalized diabetes management and improve long-term glycemic outcomes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"598614"},"PeriodicalIF":3.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789459","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":"Recent Advances in Metabolic and Bariatric Surgery: A Narrative Review of Therapeutic Strategies for Weight Loss and Metabolic Health.","authors":"Bing Zhao, Feilong Wang, Yerui Bi, Lei Li, Yabin Xia, Yan Jin","doi":"10.2147/DMSO.S613322","DOIUrl":"https://doi.org/10.2147/DMSO.S613322","url":null,"abstract":"<p><p>Metabolic and bariatric surgery (MBS) plays an important role in the management of obesity and related metabolic disorders, particularly in patients who meet established surgical criteria. The field has transitioned from open procedures to laparoscopic surgery, and the current landscape includes multiple operations with distinct efficacy-risk profiles. Alongside established procedures such as sleeve gastrectomy (SG), newer approaches-such as endoscopic metabolic interventions and robot-assisted platforms-are being evaluated for their feasibility, safety, learning curve, and potential outcome benefits. However, important questions remain regarding long-term durability, complication patterns, revisional surgery, patient selection, cost-effectiveness. To map these developments, we screened PubMed literature up to March 10, 2026 using terms such as \"metabolic and bariatric surgery\" and \"sleeve gastrectomy\", with emphasis on the International Federation for Surgery and Other Therapies for Obesity (IFSO) and higher-level evidence when available. We then synthesize findings across surgical technique evolution, indications and complications, unresolved challenges, and future directions, including how artificial intelligence (AI) and machine learning (ML) may support perioperative risk prediction and individualized treatment planning. This work aims to support clinicians in tailoring MBS plans and to guide future research priorities.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"613322"},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789518","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":"<i>Polygonati Odorati Rhizoma</i> Extract Ameliorates Obesity and Insulin Resistance Potentially Through Modulation of the TLR4/NLRP3 Signaling Pathway.","authors":"Xu Deng, Yong Wu, Xiao Chen, Jianqiang Zeng, Weihua Li, Xinghui Wang, Hua Luo, Yuntao Luo","doi":"10.2147/DMSO.S610538","DOIUrl":"https://doi.org/10.2147/DMSO.S610538","url":null,"abstract":"<p><strong>Background: </strong><i>Polygonati Odorati Rhizoma</i> (Yuzhu) is known to regulate glucose and lipid metabolism and inflammation, but its bioactive components and molecular mechanisms, particularly those involving the TLR4/NLRP3 pathway, remain unexplored. This study integrates chemical profiling, network pharmacology, and experimental validation to investigate whether and how Yuzhu extract ameliorates obesity-associated insulin resistance (IR).</p><p><strong>Methods: </strong>The chemical constituents of Yuzhu were characterized by UHPLC-Q-TOF-MS/MS. Network pharmacology integrated with GEO dataset analysis was employed to identify potential active compounds, therapeutic targets, and signaling pathways. Molecular docking was performed to evaluate compound-target interactions. A high-fat diet (HFD)-induced obese mouse model and a TNF-α-induced 3T3-L1 adipocyte inflammation model were used for experimental validation. Metabolic parameters, inflammatory cytokines, and TLR4/NLRP3 pathway-related molecules were assessed by biochemical assays, RT-qPCR, Western blot, immunohistochemistry, ELISA, and TUNEL staining.</p><p><strong>Results: </strong>A total of 127 chemical constituents were identified from Yuzhu, of which 67 met the screening criteria for potential bioactivity. Network pharmacology analysis identified 23 overlapping targets and highlighted corchorifatty acid F, 9,10-dihydroxy-12Z-octadecenoic acid, N-trans-feruloyloctopamine, and diosgenin glucoside (DG) as core active components. TLR4 and CCL2 were identified as hub targets, with significant enrichment in the NOD-like receptor signaling pathway. Molecular docking demonstrated favorable binding affinities of the core compounds to TLR4 and NLRP3, with DG exhibiting the strongest binding activity. In vivo, Yuzhu significantly reduced body weight gain, hyperglycemia, dyslipidemia, glucose intolerance, and IR in HFD-fed mice, while suppressing adipose tissue inflammation. Mechanistically, Yuzhu inhibited the expression of TLR4, MyD88, NLRP3, IL-1β, TNF-α, p-p65, p-STAT3, and cleaved caspase-1. In vitro, DG alleviated TNF-α-induced inflammatory responses and apoptosis in adipocytes, whereas recombinant HMGB1 partially reversed these protective effects.</p><p><strong>Conclusion: </strong>Yuzhu may alleviate obesity-associated IR through multi-component and multi-target regulation of the TLR4/NLRP3 signaling pathway. DG may represent a key bioactive constituent responsible for these protective effects. These findings provide mechanistic insights and experimental evidence supporting the potential application of Yuzhu in the management of metabolic disorders.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"610538"},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789426","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}