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Influence of climatic conditions on metabolite production in some Himalayan plants: a literature review. 气候条件对喜马拉雅植物代谢物产生的影响:文献综述。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-15 DOI: 10.1007/s11306-025-02375-4
Sugandh Singh, Mohd Ikram, Prakash Chand Sharma

Plants of the Himalayan region produce a wide spectrum of metabolites whose abundance is strongly influenced by species identity, genotype, developmental stage, and environmental factors such as altitude and temperature. These metabolites are of major relevance to the food, cosmetic, and pharmaceutical industries, yet their quality and composition often fluctuate with changing climatic conditions. This review synthesizes available evidence on the influence of environmental gradients particularly altitude and temperature on metabolite production in Himalayan plants, with a special emphasis on seabuckthorn (Hippophae spp.), a species of considerable commercial and pharmacological value. Unlike broader reviews of plant environment interactions, this work focuses specifically on Himalayan taxa, identifies emerging trends across metabolite classes (phenolics, flavonoids, alkaloids, terpenoids, and fatty acids), and highlights the adaptive significance of these compounds under climatic stress. In addition, 16 threatened medicinal plants of the Himalaya are considered, for which information on metabolite responses to environmental variables remains scarce. By integrating findings across species and metabolite groups, this review provides new insights into how Himalayan plants adapt to climatic challenges. Such knowledge is critical for guiding conservation strategies, optimizing cultivation practices, and ensuring the sustainable utilization of these species for nutraceutical and therapeutic applications.

喜马拉雅地区的植物产生广泛的代谢物,其丰度受物种特性、基因型、发育阶段和海拔、温度等环境因素的强烈影响。这些代谢物与食品、化妆品和制药工业密切相关,但它们的质量和成分经常随着气候条件的变化而波动。本综述综合了环境梯度,特别是海拔和温度对喜马拉雅植物代谢物产生影响的现有证据,特别强调了沙棘(Hippophae spp.),这是一种具有相当商业和药理价值的物种。与对植物与环境相互作用的广泛研究不同,这项工作特别关注喜马拉雅分类群,确定了代谢物类别(酚类、类黄酮、生物碱、萜类和脂肪酸)的新趋势,并强调了这些化合物在气候胁迫下的适应意义。此外,还考虑了喜马拉雅地区16种受威胁的药用植物,这些植物的代谢物对环境变量的反应信息仍然很少。通过整合跨物种和代谢物组的发现,本综述为喜马拉雅植物如何适应气候挑战提供了新的见解。这些知识对于指导保护策略,优化栽培方法以及确保这些物种的营养和治疗应用的可持续利用至关重要。
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引用次数: 0
Analytical practices, use and needs of standard and reference materials in the German-speaking metabolomics community: results of an online survey. 德语代谢组学社区标准和参考物质的分析实践、使用和需求:一项在线调查的结果。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-15 DOI: 10.1007/s11306-025-02360-x
Carsten Jaeger, Jutta Lintelmann, Raimo Franke, Anna Artati, Alexander Cecil, Frank Broda, Frank Klawonn, Alexander Erban, Joachim Kopka, Beate Fuchs, Ulf Sommer, Meina Neumann-Schaal, Gavin O'Connor

Introduction: Since the early 2000s, metabolomics has grown rapidly, becoming integral to fields like life sciences, health, and environmental research. This expansion has led to the formation of national and international societies, such as Germany's DGMet, to tackle emerging challenges. One of DGMet's goals is to improve measurement quality by assessing community needs for harmonization and standardization. A recent survey within the German-speaking community aimed to identify current practices and gaps in the use of chemical standards and reference materials, to guide future standardization efforts and collaborative initiatives.

Methods: An online survey was conducted between June 2023 and April 2024. The survey consisted of 38 key questions and was open to research institutions from Germany, Austria, and Switzerland.

Results: The survey was accessed by 68 laboratories, with 23 institutes providing complete or partial responses (34% response rate), which is comparable to rates reported in similar surveys within the metabolomics and lipidomics communities. Respondents were mainly experienced researchers from Germany, focusing mainly on health-related ("red") metabolomics, as indicated by 78% of the respondents, followed by microbial ("grey", 48%) and plant ("green", 39%) metabolomics (multiple answers possible). The use of targeted methods was reported more frequently (91%) than that of non-targeted methods (78%), whereas metabolite fractions studied were equally split between polar, midpolar and lipid fractions (83% each). Human (74%), mouse (61%) and Arabidopsis (30%) were the most frequently studied organisms. Most participants used synthetic chemical standards for instrument qualification (83%), calibration (78%), and metabolite identification (74%), while matrix reference materials were mainly applied for quality control (52%) and method validation (44%). There was a strong demand for more standards, especially for metabolite identification and quantification, with cost being a major barrier, particularly for isotopically labelled standards and certified reference materials.

Conclusions: Valuable insights into the use of standards and reference materials within the German-speaking metabolomics community were obtained. Moving forward, the community should address critical gaps in metabolomics standardization. To achieve this, it must share its knowledge, articulate its needs clearly, and actively engage in joint efforts with national metrology institutes and international standardization initiatives.

自21世纪初以来,代谢组学迅速发展,成为生命科学、健康和环境研究等领域不可或缺的一部分。这种扩张导致了国家和国际协会的形成,例如德国的DGMet,以应对新出现的挑战。DGMet的目标之一是通过评估社区对协调和标准化的需求来提高测量质量。最近在德语社区内进行的一项调查旨在查明目前使用化学标准和参考材料的做法和差距,以指导今后的标准化工作和合作倡议。方法:于2023年6月至2024年4月进行在线调查。该调查包括38个关键问题,并向来自德国、奥地利和瑞士的研究机构开放。结果:68个实验室访问了该调查,其中23个研究所提供了完全或部分应答(34%的应答率),这与代谢组学和脂质组学社区中类似调查报告的比率相当。受访者主要是来自德国的经验丰富的研究人员,78%的受访者表示,他们主要关注与健康相关的代谢组学(“红色”),其次是微生物(“灰色”,48%)和植物(“绿色”,39%)代谢组学(可能有多个答案)。据报道,靶向方法的使用频率(91%)高于非靶向方法(78%),而所研究的代谢物组分在极性、中极性和脂质组分之间平均分配(各83%)。人类(74%)、小鼠(61%)和拟南芥(30%)是最常被研究的生物。大多数参与者使用合成化学标准品进行仪器鉴定(83%)、校准(78%)和代谢物鉴定(74%),而基质标准品主要用于质量控制(52%)和方法验证(44%)。迫切需要更多的标准,特别是代谢物的鉴定和定量,费用是一个主要障碍,特别是同位素标记标准和核证标准物质。结论:在德语代谢组学社区中获得了使用标准和参考物质的宝贵见解。展望未来,社区应该解决代谢组学标准化方面的关键差距。为了实现这一目标,它必须分享其知识,清楚地表达其需求,并积极参与与国家计量机构和国际标准化倡议的共同努力。
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引用次数: 0
Bioactive compound identification without fractionation: an Ocimum spp. case study. 没有分离的生物活性化合物鉴定:一个菊科植物的案例研究。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-15 DOI: 10.1007/s11306-025-02369-2
Evelyn J Abraham, Kelsey Custer, R Teal Jordan, Joshua J Kellogg

Introduction: Identifying the phytochemistry underpinning a plant's observed therapeutic benefits is essential for understanding mechanisms of action and developing novel therapeutics. More recent efforts fusing global metabolomics and multivariate predictive modeling have improved compound discovery; however, these models rely on chemical variations between samples, which often necessitates at least one round of fractionation and may result in compound loss or degradation.

Objectives: This study uses multiple whole botanical extracts to explore whether a metabolome-wide association study approach can accurately identify bioactive phytochemicals without prior fractionation.

Methods: We employed 40 Ocimum extracts with a range of IC50 levels against HT-29 cells in an in vitro MTT assay and combined this data with untargeted UPLC-MS/MS metabolomics for biochemometric modeling of the potential bioactives. Multiple chemometric tools and statistical filters were employed to improve feature selection.

Results: The metabolomic profiles resulted in ca. 1600 metabolite features; implementing source-based filters, followed by LASSO dimension reduction, improved the reliability of Partial Least Squares (PLS) bioactivity predictions. The resulting model highlighted four biomarkers positively correlated with activity, one of which was putatively identified as gallic acid. Gallic acid's cytotoxicity against HT-29 cells was confirmed with the purified compound.

Conclusion: This study results demonstrated that predictive modeling of botanicals using a metabolome-wide association study of extracts with no fractionation was capable of identifying biologically active compounds.

简介:确定植物化学基础的观察到的治疗效益是理解作用机制和开发新的治疗方法至关重要。最近的努力融合了全球代谢组学和多变量预测模型,改善了化合物的发现;然而,这些模型依赖于样品之间的化学变化,这通常需要至少一轮分馏,并可能导致化合物损失或降解。目的:本研究使用多种全植物提取物来探索代谢组关联研究方法是否可以在没有事先分离的情况下准确识别生物活性植物化学物质。方法:采用40种不同IC50水平的Ocimum提取物对HT-29细胞进行体外MTT实验,并结合非靶向UPLC-MS/MS代谢组学对其潜在生物活性进行生物化学建模。使用多种化学计量工具和统计滤波器来改进特征选择。结果:代谢组学图谱显示约1600个代谢特征;实施基于源的滤波器,然后进行LASSO降维,提高了偏最小二乘(PLS)生物活性预测的可靠性。由此产生的模型突出了四个与活性正相关的生物标志物,其中一个被推定为没食子酸。纯化后的化合物证实了没食子酸对HT-29细胞的细胞毒性。结论:本研究结果表明,利用无分离提取物的全代谢组关联研究对植物药物进行预测建模能够识别出生物活性化合物。
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引用次数: 0
Identifying sex-linked metabolomic biomarkers in fish gonads after bacterial infection. 鉴定细菌感染后鱼类性腺的性别相关代谢组学生物标志物。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-15 DOI: 10.1007/s11306-025-02356-7
M Caballero-Huertas, C Ladisa, S López-Chillarón, S Joly, H R Habibi, L Ribas

Purpose: Fish aquaculture faces sustainable production challenges. Among them are the pathogenic outbreaks that can compromise the health of the stocks from various perspectives, including broodstock reproduction. This study focused on identifying the metabolite alterations produced after a bacterial infection by Vibrio anguillarum in the gonads of European seabass (Dicentrarchus labrax). Sex-related response to the infection challenge was studied using a metabolomics approach.

Method: The metabolome of testes and ovaries of adult fish were extracted and analyzed after 48 h of bacterial exposure by ultra-high-performance liquid chromatography-mass spectrometer using negative-mode electrospray ionization (ESI) (UHPLC-MS, Vanquish Horizon UHPLC coupled to a Thermo Fisher Scientific Q-Exactive HF). To further decipher the molecular events, metabolomic and transcriptomic data were interconnected.

Results: In total, 97 metabolites were identified. In the ovary, uric acid, O-phosphoethanolamine, allantoin, and acetoacetic acid were more represented. By contrast, nine metabolites were altered after the infection in testes, including uridine, N-acetylglucosamine-6-Phosphate, and Gamma-aminobutyric acid (GABA). The most abundant metabolic cascades triggered by infection in ovaries were related to glyoxylate and dicarboxylate metabolism, nitrogen metabolism, and purine metabolism, while in testes, we observed changes in glycerolipid metabolism, glycerophospholipid metabolism, and galactose metabolism.

Conclusion: The present results demonstrate, for the first time in fish, that changes in metabolic pathways induced following infection are sex-dependent. The findings will help develop sex-specific immune therapies, identify resistant phenotypes, and improve aquaculture infection protocols.

目的:水产养殖面临可持续生产挑战。其中包括病原性暴发,可从各种角度损害种群的健康,包括亲鱼的繁殖。本研究的重点是鉴定欧洲鲈鱼(Dicentrarchus labrax)生殖腺被鳗弧菌感染后产生的代谢物变化。使用代谢组学方法研究了对感染挑战的性别相关反应。方法:利用超高效液相色谱-质谱联用负模式电喷雾电离(UHPLC- ms, Vanquish Horizon UHPLC偶联Thermo Fisher Scientific Q-Exactive HF)对暴露于细菌48 h后的成鱼睾丸和卵巢代谢组进行提取和分析。为了进一步破译分子事件,代谢组学和转录组学数据相互关联。结果:共鉴定出97种代谢物。卵巢中以尿酸、磷酸乙醇胺、尿囊素、乙酰乙酸较多。相比之下,感染后睾丸中9种代谢物发生改变,包括尿苷、n -乙酰氨基葡萄糖-6-磷酸和γ -氨基丁酸(GABA)。卵巢感染引发的最丰富的代谢级联与乙醛酸盐和二羧酸盐代谢、氮代谢和嘌呤代谢有关,而在睾丸中,我们观察到甘油脂代谢、甘油磷脂代谢和半乳糖代谢的变化。结论:目前的研究结果首次在鱼类中证明了感染后代谢途径的变化是性别依赖的。这些发现将有助于开发性别特异性免疫疗法,识别耐药表型,并改进水产养殖感染方案。
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引用次数: 0
Rigor, respect and responsible reviewing for Metabolomics: essential tips for peer review success. 严谨、尊重和负责任的代谢组学评审:同行评审成功的基本技巧。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-14 DOI: 10.1007/s11306-025-02349-6
Royston Goodacre, Roan Louw
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引用次数: 0
Metabolites and MRI-derived markers of dementia risk in a Puerto Rican cohort. 波多黎各队列中痴呆风险的代谢物和mri衍生标记物。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-13 DOI: 10.1007/s11306-025-02240-4
Scott Gordon, Jong Soo Lee, Tammy M Scott, Shilpa Bhupathiraju, Jose Ordovas, Rachel S Kelly, Rafeeque Bhadelia, Bang Bon Koo, Sherman Bigornia, Katherine L Tucker, Natalia Palacios

Objective: Metabolomic risk factors for dementia are under studied, especially in Latinos. We examined the relationship between plasma metabolomic profiles and a Magnetic-Resonance Imaging (MRI)-based markers of brain aging in a cohort of older adult Puerto Ricans residing in the greater Boston area.

Methods: We used multiple linear regression, adjusted for covariates, to examine the association between metabolite concentration and MRI-derived brain age deviation. Metabolites were measured at baseline with untargeted metabolomic profiling (Metabolon, Inc). Brain age deviation was calculated at wave 4 (~ 9 years from Boston Puerto Rican Health Study (BPRHS) baseline) as chronologic age, minus MRI-estimated brain age, representing the rate of biological brain aging relative to chronologic age. We also examined if metabolites associated with brain age deviation were similarly associated with hippocampal volume and global cognitive function.

Results: Several metabolites, including isobutyrylcarnitine, propionylcarnitine, phenylacetylglutamine, phenylacetylcarnitine (acetylated peptides), p-cresol-glucuronide, phenylacetylglutamate, and trimethylamine N-oxide (TMAO) were associated with worse brain aging. Taurocholate sulfate, a bile salt, was marginally associated with better brain aging. Most metabolites with negative associations with brain age deviation also were inversely, although not significantly, associated with hippocampal volume and cognitive function.

Conclusion: The metabolites associated with brain aging in this study are generally consistent with prior literature and highlight the potential role of TMAO, BCAA and other microbially derived metabolites in dementia.

目的:痴呆症的代谢组学危险因素正在研究中,尤其是拉丁美洲人。我们研究了一组居住在大波士顿地区的波多黎各老年人的血浆代谢组学特征与基于核磁共振成像(MRI)的脑衰老标志物之间的关系。方法:我们使用多元线性回归,调整协变量,检验代谢物浓度与mri衍生的脑年龄偏差之间的关系。代谢物在基线时通过非靶向代谢组学分析(Metabolon, Inc)进行测量。脑年龄偏差在第4波(距波士顿波多黎各健康研究(BPRHS)基线约9年)计算为实际年龄,减去mri估计的脑年龄,代表相对于实际年龄的生物脑衰老率。我们还研究了与脑年龄偏差相关的代谢物是否与海马体积和整体认知功能相似。结果:几种代谢物,包括异丁基肉碱、丙酰基肉碱、苯乙酰谷氨酰胺、苯乙酰肉碱(乙酰化肽)、对甲酚-葡萄糖醛酸盐、苯乙酰谷氨酸和三甲胺n -氧化物(TMAO)与脑老化加剧有关。硫酸牛磺胆酸盐,一种胆汁盐,与更好的大脑老化有轻微的联系。大多数与脑年龄偏差呈负相关的代谢物也与海马体积和认知功能呈负相关,尽管不显著。结论:本研究中与脑衰老相关的代谢物与既往文献基本一致,并突出了TMAO、BCAA等微生物衍生代谢物在痴呆中的潜在作用。
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引用次数: 0
Retraction Note: Harnessing NMR technology for enhancing field crop improvement: applications, challenges, and future perspectives. 利用核磁共振技术加强田间作物改良:应用、挑战和未来展望。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-10 DOI: 10.1007/s11306-025-02378-1
Vedant Gautam, Vibhootee Garg, Nitesh Meena, Sunidhi Kumari, Shubham Patel, Mukesh, Himanshu Singh, Shreyashi Singh, R K Singh
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引用次数: 0
Applications of metabolomics in cow health assessment. 代谢组学在奶牛健康评估中的应用。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-08 DOI: 10.1007/s11306-025-02364-7
Xiaorui Zhao, Paraskevi Tsermoula, Bekzod Khakimov

Background: The dairy cow is an integral part of the global agricultural economy and plays a vital role in human nutrition. Compromised health in dairy cows leads to substantial economic losses and adverse environmental impacts. Understanding cow physiology and the etiology of common diseases is essential for developing effective strategies to improve animal health and mitigate negative consequences. Over the past two decades, metabolomics has emerged as a powerful approach not only for assessing and monitoring the health status of dairy cows but also for predicting and diagnosing diseases.

Aim of review: To review current metabolomics research aimed at improving the understanding of cow health status and metabolic changes associated with common diseases in dairy cows.

Key scientific concept of review: This review discusses findings from nearly 100 studies that report metabolic changes linked to health status and common diseases in dairy cows. It focuses on disease-specific metabolite alterations across different biofluids in conditions such as mastitis, lameness, acidosis, ketosis, and hypocalcemia, highlighting their relevance to pathological significance. The review also discusses how metabolomics can support early diagnosis and examines metabolic shifts related to physiological factors such as pregnancy, lactation, transition period, and parity.

背景:奶牛是全球农业经济不可分割的一部分,在人类营养中起着至关重要的作用。奶牛健康受损导致了巨大的经济损失和不利的环境影响。了解奶牛的生理和常见疾病的病因对于制定有效的策略来改善动物健康和减轻负面影响至关重要。在过去的二十年里,代谢组学已经成为一种强大的方法,不仅用于评估和监测奶牛的健康状况,而且还用于预测和诊断疾病。综述目的:综述代谢组学研究现状,旨在提高对奶牛健康状况和与奶牛常见疾病相关的代谢变化的认识。综述的关键科学概念:本综述讨论了近100项研究的发现,这些研究报告了与奶牛健康状况和常见疾病相关的代谢变化。它侧重于不同生物体液中疾病特异性代谢物的改变,如乳腺炎、跛行、酸中毒、酮症和低钙血症,强调其与病理意义的相关性。该综述还讨论了代谢组学如何支持早期诊断,并检查与生理因素(如妊娠、哺乳期、过渡期和胎次)相关的代谢变化。
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引用次数: 0
Exploring the potential relationship between serum biomarkers in obese individuals and cancer using FTIR, metabolomics, and lipidomics. 利用FTIR、代谢组学和脂质组学探索肥胖个体血清生物标志物与癌症之间的潜在关系。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-03 DOI: 10.1007/s11306-025-02351-y
Maria Eduarda Marques, Natália Ferreira Silva, Fernanda Naves Araújo do Prado Mascarenhas, Tatiana Carla Tomiosso, Robson José de Oliveira Júnior, Ricardo Rodrigues, Hebreia Oliveira Almeida-Souza, Mário Machado Martins, Luciana Machado Bastos, Arlene Bispo Dos Santos Nossol, Tiara da Costa Silva, Camila Moreira de Andrade, Marco Fidel Guevara-Vega, Robinson Sabino-Silva, Carlos Ueira-Vieira, Renata Graciele Zanon

Introduction: Robust evidence endorsed by the International Agency for Research on Cancer demonstrates that excess body fat represents a risk for the development of at least 13 types of cancer.

Objective: We investigated the serum of individuals with obesity who had no history of cancer (either personal or familial) to identify biomarkers.

Methods: 45 individuals were included in this study; they did not show significant differences regarding age, sex, or physical activity. A quality-of-life questionnaire was administered to all participants, revealing that the obese group self-reported difficulties in functional capacity and a greater association with comorbidities, notably hypertension. FTIR, metabolomic, and lipidomic analyses were performed to identify spectral peaks, metabolic, and lipids differentiating between the NO (non-obese) and OB (obese) groups.

Results: The identified peaks are predominantly associated with profiles of lipids, carbohydrates, and nitrogenous compounds. A total of six metabolites and lipids were identified at different levels in the serum of the OB group that have a direct relationship with the development or metabolism of cancer cells (three metabolites and three lipids). Among these, some suggest a reduced likelihood of cancer development, while others indicate an increased potential for cancer development. In this context, we can highlight two substances: the metabolite 4-Hydroxyphenylglyoxylate, which is reduced in the serum of individuals with obesity, and the lipid Glycidyl palmitate, which is elevated in individuals with obesity.

Conclusion: 4-Hydroxyphenylglyoxylate and Glycidyl palmitate can be used as biomarkers for cancer and obesity correlation. New experiments manipulating these substances may contribute to a better understanding of their interactions with cancer cells.

导读:国际癌症研究机构(International Agency for Research on Cancer)认可的有力证据表明,体内脂肪过多会增加患至少13种癌症的风险。目的:研究无癌症史(个人或家族)肥胖个体的血清,以确定生物标志物。方法:本研究纳入45例个体;他们在年龄、性别或身体活动方面没有显着差异。对所有参与者进行了一份生活质量问卷调查,结果显示肥胖组自我报告的功能障碍以及与合并症(尤其是高血压)的更大关联。FTIR、代谢组学和脂质组学分析用于鉴别NO(非肥胖)组和OB(肥胖)组之间的光谱峰、代谢和脂质差异。结果:鉴定出的峰主要与脂质、碳水化合物和氮化合物有关。在OB组的血清中,共鉴定出6种不同水平的代谢物和脂质与癌细胞的发生或代谢有直接关系(3种代谢物和3种脂质)。在这些研究中,一些研究表明癌症发展的可能性降低,而另一些则表明癌症发展的可能性增加。在这种情况下,我们可以强调两种物质:代谢产物4-羟基苯基乙醛酸盐,在肥胖个体的血清中减少,脂质棕榈酸缩水甘油酯,在肥胖个体中升高。结论:4-羟基苯基乙醛酸酯和棕榈酸缩水甘油酯可作为癌症与肥胖相关性的生物标志物。操纵这些物质的新实验可能有助于更好地了解它们与癌细胞的相互作用。
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引用次数: 0
Increased 1-deoxysphingolipids caused by an altered plasma alanine to serine ratio are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). 血浆丙氨酸与丝氨酸比值改变引起的1-脱氧鞘脂升高与代谢功能障碍相关的脂肪变性肝病(MASLD)有关。
IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-02 DOI: 10.1007/s11306-025-02359-4
F Wipfli, M A Lone, A von Eckardstein, A Verrijken, S Francque, J Weyler, L Van Gaal, B Staels, T Hornemann

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (formerly Non-Alcoholic Fatty Liver Disease, NAFLD) encompasses a spectrum of metabolic disorders ranging from isolated steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), potentially progressing to cirrhosis and hepatocellular carcinoma (HCC). In this study, we investigated metabolic changes in MASLD by analysing plasma lipidomics and metabolomics profiles from 315 biopsy-characterized patients. We observed significant alterations in alanine/serine (ala/ser) ratio, 1-deoxysphingolipids, alanine aminotransferase (ALT), and waist/hip ratio (whr) between patients with and without MASH. These findings highlight a close interplay between amino acid metabolism and sphingolipid biosynthesis in MASLD progression. The shift in ala/ser ratio particularly distinguished non-MASH from borderline MASH patients, suggesting that early metabolic disruptions precede overt liver damage. Additionally, elevated branched-chain and aromatic amino acids correlated with steatosis severity, reinforcing the central role of amino acid dysregulation in MASLD. While a simple model combining ALT, ala/ser ratio, and whr showed some potential to support risk stratification, the primary significance of our findings lies in the mechanistic insights into metabolic dysfunction. In conclusion, this study emphasizes the importance of metabolic network alterations in MASLD and points toward future opportunities for both mechanistic research and the development of supportive diagnostic strategies.

代谢功能障碍相关脂肪性肝病(MASLD)(原非酒精性脂肪性肝病,NAFLD)包括一系列代谢性疾病,从孤立的脂肪变性到代谢功能障碍相关脂肪性肝炎(MASH),可能进展为肝硬化和肝细胞癌(HCC)。在这项研究中,我们通过分析315例活检患者的血浆脂质组学和代谢组学特征来研究MASLD的代谢变化。我们观察到有和没有MASH的患者在丙氨酸/丝氨酸(ala/ser)比率、1-脱氧鞘脂、丙氨酸转氨酶(ALT)和腰/臀比(whr)方面的显著变化。这些发现强调了氨基酸代谢和鞘脂生物合成在MASLD进展中的密切相互作用。ala/ser比值的变化特别区分了非MASH和临界MASH患者,表明早期代谢紊乱先于明显的肝损害。此外,支链和芳香氨基酸的升高与脂肪变性的严重程度相关,强化了氨基酸失调在MASLD中的核心作用。虽然结合ALT、ala/ser比率和whr的简单模型显示出支持风险分层的一些潜力,但我们的研究结果的主要意义在于对代谢功能障碍的机制见解。总之,本研究强调了MASLD中代谢网络改变的重要性,并指出了未来机制研究和支持性诊断策略发展的机会。
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引用次数: 0
期刊
Metabolomics
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