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Impact of a virtual Culinary medicine curriculum on fatty acid profiles in medical students 虚拟烹饪医学课程对医学生脂肪酸谱的影响
IF 2.7 Pub Date : 2025-12-09 DOI: 10.1016/j.metop.2025.100431
Selina Böttcher , Thomas Ellrott , Miriam Rabehl , Can G. Leineweber , Chaoxuan Wang , Uwe Neumann , Anne Pietzner , Christoph Schmöcker , Karsten H. Weylandt

Background

Culinary Medicine (CM) has gained increasing popularity as an educational approach to improve nutrition-related competencies among healthcare professionals. Previous studies have demonstrated increased counseling competencies, but also improvements in dietary behaviors among participants, however, objective biomarker-based evidence of such behavioral changes remains scarce. This pilot study aimed to explore preliminary effects of a CM course on biochemical and anthropometric parameters, and to evaluate the feasibility of biomarker assessment among medical students.

Methods

In this exploratory pre-post study, medical students completed a 20-h virtual CM curriculum. Blood samples were collected before and after the course to assess lipid parameters, HbA1c, erythrocyte fatty acid compositions, and body weight.

Results

Of 30 enrolled students, 13 participated in the biomarker assessment. There were slight non-significant decreases in Body Mass Index (−0.08 kg/m2, p = 0.07) and standard laboratory lipid parameters, including LDL Cholesterol (−0.08 mmol/L, p = 0.598) and total cholesterol (−0.12 mmol/L, p = 0.493). Significant alterations in erythrocyte fatty acids were detected with a slight increase in saturated fatty acids (+0.78 %, p = 0.004) and, in particular, monounsaturated fatty acids (+1.04 %, p = 0.004), accompanied by a significant decrease in n-6 polyunsaturated fatty acids (−2.28 %, p = 0.003).

Discussion

This pilot study demonstrates the feasibility of conducting biomarker-based evaluations within a CM curriculum and provides preliminary biochemical evidence supporting previous self-reported findings of dietary behavior change. The study illustrates a promising approach for integrating objective outcome measures into CM education and informs the design of future, adequately powered trials.
背景烹饪医学(CM)作为一种提高医疗保健专业人员营养相关能力的教育方法越来越受欢迎。先前的研究已经证明了咨询能力的提高,以及参与者饮食行为的改善,然而,基于生物标志物的这种行为改变的客观证据仍然很少。本初步研究旨在探讨CM课程对医学生生化及人体测量参数的初步影响,并评估生物标志物评估的可行性。方法在这项探索性的岗前研究中,医学生完成了20小时的虚拟CM课程。在疗程前后采集血样,评估血脂参数、糖化血红蛋白、红细胞脂肪酸组成和体重。结果30名在校生中,13名参加了生物标志物评估。体重指数(- 0.08 kg/m2, p = 0.07)和标准实验室脂质参数,包括低密度脂蛋白胆固醇(- 0.08 mmol/L, p = 0.598)和总胆固醇(- 0.12 mmol/L, p = 0.493)有轻微的无显著性下降。红细胞脂肪酸发生显著变化,饱和脂肪酸略有增加(+ 0.78%,p = 0.004),尤其是单不饱和脂肪酸(+ 1.04%,p = 0.004),同时n-6多不饱和脂肪酸显著减少(- 2.28%,p = 0.003)。本初步研究证明了在CM课程中进行基于生物标志物的评估的可行性,并提供了初步的生化证据,支持先前饮食行为改变的自我报告结果。该研究阐明了一种将客观结果测量纳入CM教育的有希望的方法,并为未来设计提供了充分动力的试验。
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引用次数: 0
Machine learning–based binary classification of elevated HbA1c (≥6.5 %) for risk assessment 基于机器学习的HbA1c升高(≥6.5%)二元分类风险评估
IF 2.7 Pub Date : 2025-12-09 DOI: 10.1016/j.metop.2025.100428
Dler Hussein Kadir , Azhin Mohammed Khudhur , Hewir Abdulqadir Khidir

Objective

One of the most important biomarkers for evaluating long-term glycemic management and estimating the risk of diabetes is glycated hemoglobin (HbA1c). Early risk assessment and intervention techniques can be improved by identifying important clinical and demographic variables. Through the integration of clinical indicators (lipid profiles, albumin, and liver enzymes) and demographic characteristics (age, gender), this study seeks to create a comprehensive HbA1c prediction model.

Study design

To find the most important factors, logistic regression was used to evaluate 482 cases using a stepwise selection process.

Results

With an area under the curve (AUC) of 0.797, the final model had strong predictive ability. Age (OR = 1.085, p < 0.001), glutamate pyruvate transaminase (GPT) (OR = 1.011, p = 0.0127), high-density lipoprotein (HDL) (OR = 0.969, p = 0.017), VitaminD3 (OR = 1.023, p = 0.014), and very low-density lipoprotein (VDL) (OR = 1.016, p = 0.018) were all significant predictors.

Conclusions

The greatest predictor was age, which was positively correlated with elevated HbA1c levels, whereas HDL had a protective impact. The addition of VitaminD3, VDL, and GPT implies that indicators of liver and metabolic function have a major role in the variability of HbA1c. These results demonstrate how normal clinical and demographic data may be incorporated into predictive models for early diabetes risk assessment, enabling more individualized medical care and bettering patient outcomes.
目的糖化血红蛋白(HbA1c)是评估长期血糖管理和评估糖尿病风险的最重要的生物标志物之一。通过识别重要的临床和人口变量,可以改进早期风险评估和干预技术。通过整合临床指标(血脂、白蛋白和肝酶)和人口统计学特征(年龄、性别),本研究试图建立一个全面的HbA1c预测模型。为了找出最重要的因素,采用逐步选择方法对482例病例进行了logistic回归评估。结果最终模型的曲线下面积(AUC)为0.797,预测能力较强。年龄(OR = 1.085, p < 0.001)、谷氨酸丙酮酸转氨酶(GPT) (OR = 1.011, p = 0.0127)、高密度脂蛋白(HDL) (OR = 0.969, p = 0.017)、维生素d3 (OR = 1.023, p = 0.014)、极低密度脂蛋白(VDL) (OR = 1.016, p = 0.018)均为显著预测因子。结论年龄是最大的预测因子,与HbA1c水平升高呈正相关,而HDL具有保护作用。维生素ind3、VDL和GPT的加入表明肝脏和代谢功能指标在HbA1c变变性中起主要作用。这些结果证明了如何将正常的临床和人口统计数据纳入早期糖尿病风险评估的预测模型,从而实现更个性化的医疗护理和更好的患者预后。
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引用次数: 0
Breakpoint-resolved balanced t(2;12)(q35;q24.31) disrupting HNF1A in multigenerational MODY-3: Diagnostic utility of long-read genome sequencing and therapeutic impact 断点解决平衡t(2;12)(q35;q24.31)在多代MODY-3中破坏HNF1A:长读基因组测序的诊断效用和治疗影响
IF 2.7 Pub Date : 2025-12-09 DOI: 10.1016/j.metop.2025.100430
Pamela Rivero-García , Osvaldo M. Mutchinick , Eira Huerta-Ávila , Ilse A. Colorado , Cristy Alfonso-López , Renata Rivera-Juárez , Virginia Santiago-Cano , Juan José Morales-Suárez , Alfredo Hidalgo-Miranda , Yevgeniya Svyryd
Balanced translocations that interrupt HNF1A are seldom documented in MODY-3. We studied a three-generation family with early-onset, non-autoimmune diabetes consistent with MODY-3. Conventional karyotyping revealed a balanced reciprocal translocation, t(2; 12)(q35; q24.31). We then opted for long-read genome sequencing using ONT® PromethION™ (median coverage 22X; read N50 11.4 kb), which mapped breakpoints at chr12:120,984,209 (HNF1A intron 1) and chr2:218,759,723 (intergenic region). Segregation analysis revealed that the rearrangement cosegregates with diabetes across three generations (5 affected individuals; 1 carrier). Although expression assays were not performed, disruption of HNF1A within intron 1 is most consistent with loss-of-function and haploinsufficiency in this context. After molecular diagnosis, sulfonylureas were added to the treatment regimen of four affected relatives, resulting in favorable clinical outcomes. To our knowledge, multigenerational cosegregation of a balanced translocation directly disrupting HNF1A has not been previously reported. This case introduces a breakpoint-level mechanism for MODY-3 and demonstrates why long-read sequencing is crucial when a karyotype indicates a balanced rearrangement near a monogenic diabetes locus: it resolves the structure and shortens the path to a treatment decision.
干扰HNF1A的平衡易位在MODY-3中很少被记录。我们研究了与MODY-3一致的早发性非自身免疫性糖尿病的三代家族。常规核型分析显示一个平衡的反向易位,t(2; 12)(q35; q24.31)。然后,我们选择使用ONT®PromethION™(中位覆盖率22X;读取N50 11.4 kb)进行长读基因组测序,该测序将断点定位在chr12:120,984,209 (HNF1A内含子1)和chr2:218,759,723(基因间区)。分离分析显示,重排与糖尿病共分离跨越三代(5个受影响个体;1个携带者)。虽然没有进行表达分析,但在这种情况下,内含子1内HNF1A的破坏与功能丧失和单倍功能不足最为一致。经分子诊断后,4例患病亲属在治疗方案中加入磺脲类药物,临床效果良好。据我们所知,直接破坏HNF1A的平衡易位的多代共隔离先前尚未报道。本病例介绍了MODY-3的断点水平机制,并证明了当核型表明在单基因糖尿病位点附近有平衡重排时,为什么长读测序是至关重要的:它解决了结构并缩短了治疗决策的路径。
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引用次数: 0
First European case of Geller syndrome complicated with hypokalemic nephropathy: A case report and literature review 欧洲首例盖勒综合征合并低钾血症肾病:1例报告及文献复习
IF 2.7 Pub Date : 2025-12-09 DOI: 10.1016/j.metop.2025.100429
Efstratios Gavriilidis , Christina Antoniadou , Georgia Dimopoulou , Evangelos Papadimitriou , Stefania-Aspasia Bakola , Charalampos Papagoras , Panagiotis Skendros , Dimitrios Tsilingiris
Geller syndrome is caused by a gain-of-function mutation in the mineralocorticoid receptor (MR), rendering it prone to activation by elevated progesterone levels during pregnancy. It is characterized by gestational hypertension and hypokalemia. We describe the case of a 35-year-old primigravida, who presented at 22 weeks of gestation with severe hypokalemia and hypertension, complicated by hypokalemic nephropathy manifesting as diabetes insipidus and proteinuria. Initial potassium replacement, eplerenone administration and desmopressin were insufficient, whereas the administration of amiloride, a potassium-sparing diuretic that inhibits epithelial sodium channels (ENaC) in the distal nephron, led to complete resolution of the clinical syndrome. The patient had no further complications and delivered a healthy infant at 37 weeks. Genetic testing did not reveal known MR mutations, suggesting that other genetic variants or epigenetic changes in MR may warrant future investigation, particularly in isolated populations. To date, 17 cases of Geller syndrome have been reported in the literature including the herein presented, which is to the best of our knowledge the first documented in Europe. Genetic testing was performed in only one case, apart from the initially reported ones. Urgent delivery was required in four cases, while amiloride, the treatment of choice, was administered in only five, highlighting the importance of early recognition of the syndrome for effective management and prevention of adverse pregnancy outcomes.
盖勒综合征是由矿化皮质激素受体(MR)的功能获得突变引起的,在怀孕期间,由于孕激素水平升高,该受体容易被激活。它的特点是妊娠期高血压和低钾血症。我们描述了一个35岁的初产妇,在妊娠22周时出现严重的低钾血症和高血压,并伴有低钾血症肾病,表现为尿囊症和蛋白尿。最初的钾替代、依普利酮和去氨加压素治疗不足,而阿米洛利(一种抑制远端肾元上皮钠通道(ENaC)的保钾利尿剂)的治疗导致临床综合征的完全解决。患者没有进一步的并发症,并在37周时生下了一个健康的婴儿。基因检测未发现已知的MR突变,这表明MR的其他遗传变异或表观遗传变化可能值得未来的研究,特别是在孤立人群中。迄今为止,文献中已经报道了17例盖勒综合征,包括本文所述,据我们所知,这是欧洲首次记录的病例。除了最初报道的病例外,只有一例进行了基因检测。4例需要紧急分娩,而只有5例选择了阿米洛利治疗,这突出了早期识别该综合征对有效管理和预防不良妊娠结局的重要性。
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引用次数: 0
Cross-sectional mediation analysis of systemic inflammation in the association between serum uric acid and diabetic kidney disease: Evidence from NHANES 1999–2018 血清尿酸与糖尿病肾病相关性全系统炎症的横断面中介分析:来自NHANES 1999-2018的证据
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100426
Jiaying Wang , Weijing Liu , Jiaoyan Li , Mengxiao Li , Heyan Feng , Shangfei Liu , Yanzhe Cheng , Wei Li

Objective

To investigate whether systemic inflammation, quantified by the Aggregate Index of Systemic Inflammation (AISI), mediates the association between uric acid (UA) and diabetic kidney disease (DKD).

Study design

We analyzed data from 1716 adults with diabetes in NHANES 1999–2018. We used regression to assess UA-AISI-DKD associations and mediation analysis to quantify AISI's indirect effect. A random forest model, interpreted via SHAP, predicted DKD risk.

Results

Each 1 mg/dL increase in UA was associated with a 14 % higher DKD risk (adjusted OR = 1.14, 95 % CI: 1.04–1.26). UA was positively associated with AISI (β = 0.0356, p = 0.0058), which in turn predicted DKD (OR = 1.25 per SD increase in ln-AISI, 95 % CI: 1.10–1.42). AISI partially mediates (10.94 %) the association between UA and DKD, indicating that systemic inflammation is one of several pathways linking hyperuricemia to renal injury. The random forest model performed best, with SHAP highlighting AISI as a key positive predictor.

Conclusion

Systemic inflammation, as measured by AISI, partially mediates the cross-sectional association between serum uric acid and diabetic kidney disease, supporting inflammation as one of several contributing pathways. The predictive performance of models incorporating AISI remains modest and does not outperform conventional clinical risk scores.
目的探讨全身性炎症(AISI)是否介导尿酸(UA)与糖尿病肾病(DKD)的关系。研究设计我们分析了NHANES 1999-2018年1716名成人糖尿病患者的数据。我们使用回归来评估UA-AISI-DKD的关联,并使用中介分析来量化AISI的间接影响。通过SHAP解释的随机森林模型预测了DKD风险。结果UA每增加1 mg/dL, DKD风险增加14%(调整后OR = 1.14, 95% CI: 1.04 ~ 1.26)。UA与AISI呈正相关(β = 0.0356, p = 0.0058),进而预测DKD (OR = 1.25 / SD增加ln-AISI, 95% CI: 1.10-1.42)。AISI部分介导UA和DKD之间的关联(10.94%),表明全身性炎症是连接高尿酸血症与肾损伤的几种途径之一。随机森林模型表现最好,其中SHAP突出了AISI作为关键的积极预测因子。结论AISI测量的全身性炎症部分介导了血清尿酸与糖尿病肾病之间的横断面关联,支持炎症作为几种促进途径之一。纳入AISI的模型的预测性能仍然适中,并不优于传统的临床风险评分。
{"title":"Cross-sectional mediation analysis of systemic inflammation in the association between serum uric acid and diabetic kidney disease: Evidence from NHANES 1999–2018","authors":"Jiaying Wang ,&nbsp;Weijing Liu ,&nbsp;Jiaoyan Li ,&nbsp;Mengxiao Li ,&nbsp;Heyan Feng ,&nbsp;Shangfei Liu ,&nbsp;Yanzhe Cheng ,&nbsp;Wei Li","doi":"10.1016/j.metop.2025.100426","DOIUrl":"10.1016/j.metop.2025.100426","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether systemic inflammation, quantified by the Aggregate Index of Systemic Inflammation (AISI), mediates the association between uric acid (UA) and diabetic kidney disease (DKD).</div></div><div><h3>Study design</h3><div>We analyzed data from 1716 adults with diabetes in NHANES 1999–2018. We used regression to assess UA-AISI-DKD associations and mediation analysis to quantify AISI's indirect effect. A random forest model, interpreted via SHAP, predicted DKD risk.</div></div><div><h3>Results</h3><div>Each 1 mg/dL increase in UA was associated with a 14 % higher DKD risk (adjusted OR = 1.14, 95 % CI: 1.04–1.26). UA was positively associated with AISI (β = 0.0356, p = 0.0058), which in turn predicted DKD (OR = 1.25 per SD increase in ln-AISI, 95 % CI: 1.10–1.42). AISI partially mediates (10.94 %) the association between UA and DKD, indicating that systemic inflammation is one of several pathways linking hyperuricemia to renal injury. The random forest model performed best, with SHAP highlighting AISI as a key positive predictor.</div></div><div><h3>Conclusion</h3><div>Systemic inflammation, as measured by AISI, partially mediates the cross-sectional association between serum uric acid and diabetic kidney disease, supporting inflammation as one of several contributing pathways. The predictive performance of models incorporating AISI remains modest and does not outperform conventional clinical risk scores.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100426"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of sleep quality and glycemic variability among South Indian rural patients with Type-2 diabetes mellitus 南印度农村2型糖尿病患者睡眠质量与血糖变异性的关系
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100427
Mohammed Azhar Hussain , H. Anil Kumar , Mahadevamma Lingaiah

Background

Sleep quality plays a vital role in glucose homeostasis and may influence glycemic variability among diabetic individuals. The main objective of this study is to investigate the relationship between subjective sleep quality and glycemic variability in patients with Type-2 diabetes mellitus (T2DM).

Methods

Sixty-two adults with type 2 diabetes mellitus underwent Continuous Glucose Monitoring (CGM) and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with at least three days of valid CGM data were included in the analyses. Glycemic variability was quantified using coefficient of variation (%CV). Spearman's correlation and multiple linear regression modelling were used to examine the association between glycemic variability (%CV) and sleep quality.

Results

Sleep-efficiency showed a significant positive correlation with %CV (r = 0.28, p = 0.03), whereas greater sleep disturbances were associated with lower TBR (r = −0.27, p = 0.04). A %CV threshold of 32.3 was identified as a cutoff for distinguishing stable and unstable glycemic patterns; however, this threshold is exploratory and requires further validation. In multiple linear regression analyses reduced sleep efficiency (β = 7.77, p = 0.002) was significantly associated with higher glycemic variability, while sleep medication use (β = −2.12, p = 0.01) also showed significant association after adjustment for HbA1c, microvascular and macrovascular complications.

Conclusion

Poor sleep quality, particularly sleep efficiency exhibited a significant relationship with glycemic variability. Improving sleep quality may represent a practical and modifiable strategy to improve glycemic stability in this population.
背景:睡眠质量在葡萄糖稳态中起着至关重要的作用,并可能影响糖尿病患者的血糖变异性。本研究的主要目的是探讨2型糖尿病(T2DM)患者主观睡眠质量与血糖变异性的关系。方法对62例成人2型糖尿病患者进行连续血糖监测(CGM),并采用匹兹堡睡眠质量指数(PSQI)评价其睡眠质量。具有至少三天有效CGM数据的患者被纳入分析。用变异系数(%CV)量化血糖变异性。使用Spearman相关和多元线性回归模型来检验血糖变异性(%CV)与睡眠质量之间的关系。结果睡眠效率与%CV呈显著正相关(r = 0.28, p = 0.03),而睡眠障碍越大,TBR越低(r = - 0.27, p = 0.04)。32.3的%CV阈值被确定为区分稳定和不稳定血糖模式的截止值;然而,这个阈值是探索性的,需要进一步验证。在多元线性回归分析中,睡眠效率降低(β = 7.77, p = 0.002)与较高的血糖变异性显著相关,而睡眠药物使用(β = - 2.12, p = 0.01)在调整HbA1c、微血管和大血管并发症后也显示出显著相关性。结论睡眠质量差,尤其是睡眠效率差与血糖变异性有显著关系。改善睡眠质量可能是改善这一人群血糖稳定性的一种实用且可修改的策略。
{"title":"Association of sleep quality and glycemic variability among South Indian rural patients with Type-2 diabetes mellitus","authors":"Mohammed Azhar Hussain ,&nbsp;H. Anil Kumar ,&nbsp;Mahadevamma Lingaiah","doi":"10.1016/j.metop.2025.100427","DOIUrl":"10.1016/j.metop.2025.100427","url":null,"abstract":"<div><h3>Background</h3><div>Sleep quality plays a vital role in glucose homeostasis and may influence glycemic variability among diabetic individuals. The main objective of this study is to investigate the relationship between subjective sleep quality and glycemic variability in patients with Type-2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>Sixty-two adults with type 2 diabetes mellitus underwent Continuous Glucose Monitoring (CGM) and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with at least three days of valid CGM data were included in the analyses. Glycemic variability was quantified using coefficient of variation (%CV). Spearman's correlation and multiple linear regression modelling were used to examine the association between glycemic variability (%CV) and sleep quality.</div></div><div><h3>Results</h3><div>Sleep-efficiency showed a significant positive correlation with %CV (r = 0.28, p = 0.03), whereas greater sleep disturbances were associated with lower TBR (r = −0.27, p = 0.04). A %CV threshold of 32.3 was identified as a cutoff for distinguishing stable and unstable glycemic patterns; however, this threshold is exploratory and requires further validation. In multiple linear regression analyses reduced sleep efficiency (β = 7.77, p = 0.002) was significantly associated with higher glycemic variability, while sleep medication use (β = −2.12, p = 0.01) also showed significant association after adjustment for HbA1c, microvascular and macrovascular complications.</div></div><div><h3>Conclusion</h3><div>Poor sleep quality, particularly sleep efficiency exhibited a significant relationship with glycemic variability. Improving sleep quality may represent a practical and modifiable strategy to improve glycemic stability in this population.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100427"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease 以毒攻毒:抑制PLA2G15调动BMP脂质对抗NPC1疾病
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100390
Wei Meng , Junli Liu , Xun Huang
{"title":"Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease","authors":"Wei Meng ,&nbsp;Junli Liu ,&nbsp;Xun Huang","doi":"10.1016/j.metop.2025.100390","DOIUrl":"10.1016/j.metop.2025.100390","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100390"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deoxycholic Acid and Lipoteichoic Acid cooperatively drive macrophage M2/M1 polarization via TGR5/STAT3 and TLR2/NF-κB to fuel HCC progression in obesity 去氧胆酸和脂质胆酸通过TGR5/STAT3和TLR2/NF-κB共同驱动巨噬细胞M2/M1极化,促进肥胖患者HCC进展
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100420
Jian Wu , wen Zheng , Xu-zhen Ding , Qiao-ping Jin , Ming-xing Ding

Background

Obesity-related hepatocellular carcinoma (HCC) is associated with gut microbiota dysbiosis. However, the specific roles of key microbial metabolites, deoxycholic acid (DCA) and lipoteichoic acid (LTA), in modulating the immune microenvironment and promoting HCC progression are not fully understood.

Aim

This study aimed to elucidate the synergistic effects and mechanisms of DCA and LTA in obesity-related HCC.

Methods

An obesity-related HCC model was established in mice using a high-fat diet combined with diethylnitrosamine. In vitro, macrophage and HCC cell co-culture systems were utilized, along with gene knockdown approaches.

Results

Combined DCA and LTA treatment synergistically exacerbated liver fibrosis and tumorigenesis in the mouse model. This was accompanied by suppressed expression of Cdkn1a and Cdkn2a, and activation of GPC-3 and CD44. Mechanistically, DCA promoted M2 macrophage polarization via the TGR5-STAT3 axis, whereas LTA drove M1 polarization via TLR2-NF-κB. In co-culture, knockdown of TLR2 and TGR5 reversed the pro-tumorigenic effects of DCA and LTA, inhibiting the epithelial-mesenchymal transition and reducing cancer cell invasion.

Conclusion

DCA and LTA synergistically promote HCC progression in obesity by co-modulating the TLR2-TGR5 signaling axis in macrophages, thereby reshaping the tumor immune microenvironment.
背景:肥胖相关性肝细胞癌(HCC)与肠道菌群失调有关。然而,关键微生物代谢物脱氧胆酸(DCA)和脂磷胆酸(LTA)在调节免疫微环境和促进HCC进展中的具体作用尚不完全清楚。目的探讨DCA和LTA在肥胖相关性肝癌中的协同作用及其机制。方法采用高脂饮食联合二乙基亚硝胺建立小鼠肥胖相关肝癌模型。在体外,利用巨噬细胞和HCC细胞共培养系统,以及基因敲低方法。结果DCA和LTA联合治疗可协同加重小鼠肝纤维化和肿瘤发生。这伴随着Cdkn1a和Cdkn2a的表达抑制,以及GPC-3和CD44的激活。在机制上,DCA通过TGR5-STAT3轴促进M2巨噬细胞极化,而LTA通过TLR2-NF-κB轴促进M1极化。在共培养中,TLR2和TGR5的下调逆转了DCA和LTA的致瘤作用,抑制了上皮-间质转化,减少了癌细胞的侵袭。结论dca和LTA通过共同调节巨噬细胞中TLR2-TGR5信号轴,协同促进肥胖HCC进展,从而重塑肿瘤免疫微环境。
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引用次数: 0
Corrigendum to “Prevalence of normal weight obesity among adults in Southeast Asia: Insights from a systematic review and meta-analysis” [Metabol. Open 28C (2025) 100416] “东南亚成年人中正常体重肥胖的患病率:来自系统回顾和荟萃分析的见解”的勘误表。打开28C (2025) 100416]
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100425
K.G. Sruthi , C. Aditya , Paramjot Panda , Jyoti Ranjan Mohanty , Manas Ranjan Behera
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引用次数: 0
Gestational diabetes alters prefrontal neurochemistry and disrupts maternal behaviors: Role of Fibrillin-1, serotonin, and TNF-α in rats 妊娠期糖尿病改变大鼠前额叶神经化学并扰乱母体行为:纤原蛋白-1、血清素和TNF-α的作用
IF 2.7 Pub Date : 2025-12-01 DOI: 10.1016/j.metop.2025.100422
Samira Khayat , Hamed Fanaei , Abdolvahed Safarzaei

Objective

Gestational diabetes mellitus (GDM) is a metabolic disorder that can impact various aspects of maternal behavior and neurochemical processes. This study aimed to investigate the effects of GDM on FBN1 (fibrillin-1) gene expression, TNF-alpha, serotonin and maternal behavior in rat.

Materials and methods

A total of twenty female Wistar rats were randomly divided into two groups: the control group and the gestational diabetes mellitus (GDM) group. The study compared maternal behavior patterns between the GDM and control groups and measured the following in the hippocampus and prefrontal cortex: TNF-α and serotonin levels (via ELISA), and FBN1 mRNA expression (via qRT-PCR).

Results

The findings demonstrated that TNF-α levels (P = 0.0025) were significantly higher in the prefrontal cortex of the GDM group compared to the control group, whereas serotonin levels (P = 0.0037) were significantly lower. Additionally, FBN1 mRNA expression levels (P = 0.012) in the prefrontal cortex of GDM group were significantly higher than those in the control group. In terms of maternal behavior, the GDM group exhibited weakened behaviors compared to the control group. Specifically, endurance of maternal behaviors such as the duration of breastfeeding (P = 0.024), nesting (P = 0.016), and pup grooming (P = 0.017) were significantly decreased in the GDM group compared to control group. The speed of integration of maternal behaviors, specifically the latency to onset of pup retrieval (P = 0.0018), significantly increased, while the number of breastfeeding instances (P = 0.0026) significantly decreased in the GDM group compared to the control group. Furthermore, the emotionality (self-calming) aspect of maternal behavior, specifically self-grooming, exhibited a significant decreases in both duration (P = 0.0097) and number of instances (P = 0.0029) in the GDM group compared to the control group. In the hippocampus, only TNF-α levels were significantly elevated in the GDM group (P = 0.0003); no significant differences were found in serotonin or FBN1 mRNA expression.

Conclusion

These results demonstrate that GDM significantly dysregulates prefrontal cortex neurochemistry (increasing TNF-α and FBN1 mRNA while decreasing serotonin) and profoundly weakens maternal behavior, affecting its endurance, speed of integration, and emotional components in rats.
目的:植物性糖尿病(GDM)是一种影响母体行为和神经化学过程的代谢性疾病。本研究旨在探讨GDM对大鼠FBN1(纤原蛋白-1)基因表达、tnf - α、血清素及母性行为的影响。材料与方法选用雌性Wistar大鼠20只,随机分为对照组和妊娠期糖尿病(GDM)组。该研究比较了GDM组和对照组之间的母亲行为模式,并测量了海马和前额皮质的以下指标:TNF-α和血清素水平(通过ELISA),以及FBN1 mRNA表达(通过qRT-PCR)。结果GDM组前额叶皮层TNF-α水平显著高于对照组(P = 0.0025),血清素水平显著低于对照组(P = 0.0037)。GDM组大鼠前额叶皮层FBN1 mRNA表达量显著高于对照组(P = 0.012)。在母性行为方面,GDM组表现出较对照组弱的行为。其中,与对照组相比,GDM组母性行为的持续时间(P = 0.024)、筑巢时间(P = 0.016)和幼崽梳理时间(P = 0.017)均显著降低。与对照组相比,GDM组母性行为整合的速度,特别是幼崽检索开始的潜伏期(P = 0.0018)显著增加,而母乳喂养次数(P = 0.0026)显著减少。此外,与对照组相比,GDM组的母性行为的情绪(自我镇静)方面,特别是自我梳理,在持续时间(P = 0.0097)和实例数量(P = 0.0029)上都显着减少。在海马中,GDM组只有TNF-α水平显著升高(P = 0.0003);血清素和FBN1 mRNA表达无显著差异。结论GDM显著失调大鼠前额叶皮层神经化学(升高TNF-α和FBN1 mRNA,降低血清素),严重削弱母性行为,影响其耐力、整合速度和情绪成分。
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引用次数: 0
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Metabolism open
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