Redox Biology最新文献

{"title":"Glucagon-like peptide-1 receptor signaling activation in alveolar type II cells enhances lung development in neonatal rats exposed to hyperoxia","authors":"Tong Sun , Haiyang Yu , Dingning Zhang , Dan Zhang , Danni Li , Jianhua Fu","doi":"10.1016/j.redox.2025.103586","DOIUrl":"10.1016/j.redox.2025.103586","url":null,"abstract":"<div><h3>Background</h3><div>Many studies have reported the important role of glucagon-like peptide-1 receptor (GLP-1R) in regulating glucose homeostasis. However, in addition to the pancreas, GLP-1R is distributed in organs such as the lungs. A few researches have reported the mechanism of action of GLP-1R in acute and chronic lung diseases. Nevertheless, its effect on lung development remains unclear. In this research, we aimed to explore the role of GLP-1R in regulating lung development and its potential mechanisms in <em>in vivo</em> and <em>in vitro</em> bronchopulmonary dysplasia (BPD) models.</div></div><div><h3>Methods</h3><div>Neonatal Sprague-Dawley rats were divided into hyperoxia (FIO2 = 0.85) and control (FIO2 = 0.21) groups. Lung tissues were extracted at 3, 7, 10, and 14 postnatal days and subjected to hematoxylin and eosin staining for histopathological and morphological observation. Single-cell RNA sequencing was performed to explore the role of GLP-1R in lung development. Western blotting was conducted to assess the expression of GLP-1R, dynamin-related protein 1 (DRP1), and glycolysis-associated enzymes, including phosphofructokinase (PFKM), hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), in the lung tissues, primary alveolar type II (ATII) cells, and RLE-6TN cells. Double immunofluorescence staining was performed to confirm the co-localization of GLP-1R, DRP1, and ATII cells. A Seahorse XF96 metabolic extracellular flux analyzer was used to perform real-time analyses of extracellular acidification rate and oxygen consumption rate in ATII cells isolated from lung tissues and RLE-6TN cells. The adenosine triphosphate (ATP) concentrations in ATII and RLE-6TN cells were measured using an ATP kit. Mitochondria were stained with MitoTracker and observed using HiS-SIM. GLP-1R gene levels in lung tissues, primary ATII cells, and RLE-6TN cells were tested using RT-qPCR. We used MeRIP-qPCR to determine the m6A modification level of GLP-1R mRNA in RLE-6TN cells. A reporter gene was used to verify the modification site and key methyltransferases.</div></div><div><h3>Results</h3><div>We observed that GLP-1R signaling regulates lung development and plays a key role in ATII cells, particularly after birth. Hyperoxia inhibits GLP-1R protein and gene expression in ATII cells and accelerates BPD development. ATP production decreased and glycolysis levels increased in ATII cells under hyperoxia. Activation of GLP-1R signaling promotes ATP production and downregulates glycolysis by regulating DRP1 induced mitochondria fission. In RLE-6TN cells, we verified that the m6A modification level of GLP-1R mRNA decreased; the modification site was tested by MeRIP-qPCR and was primarily induced by the methyltransferase-like 14 (METTL14).</div></div><div><h3>Conclusion</h3><div>GLP-1R is primarily expressed in ATII cells of neonatal rats and can promote lung development during the early postnatal period. The GLP-1R signaling pathway modulates mitoch","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103586"},"PeriodicalIF":10.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Cancer Potential of a new Derivative of Caffeic Acid Phenethyl Ester targeting the Centrosome","authors":"Catello Giordano ,&nbsp;Jonatan Kendler ,&nbsp;Maximilian Sexl ,&nbsp;Sebastian Kollman ,&nbsp;Maxim Varenicja ,&nbsp;Boglárka Szabó ,&nbsp;Gerald Timelthaler ,&nbsp;Dominik Kirchhofer ,&nbsp;Oldamur Hollóczki ,&nbsp;Suzanne D. Turner ,&nbsp;Richard Moriggl ,&nbsp;Lukas Kenner ,&nbsp;Mohamed Touaibia ,&nbsp;Olaf Merkel","doi":"10.1016/j.redox.2025.103582","DOIUrl":"10.1016/j.redox.2025.103582","url":null,"abstract":"<div><div>Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal γ-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103582"},"PeriodicalIF":10.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort","authors":"Jialin Li ,&nbsp;Qiuhong Man ,&nbsp;Yingzhe Wang ,&nbsp;Mei Cui ,&nbsp;Jincheng Li ,&nbsp;Kelin Xu ,&nbsp;Zhenqiu Liu ,&nbsp;Li Jin ,&nbsp;Xingdong Chen ,&nbsp;Chen Suo ,&nbsp;Yanfeng Jiang","doi":"10.1016/j.redox.2025.103585","DOIUrl":"10.1016/j.redox.2025.103585","url":null,"abstract":"<div><div>Metabolic malnutrition and inflammation—key mechanism links to redox imbalance—are fundamental pathologies that accelerate aging and disease progression, ultimately leading to death. The recently proposed metabolic vulnerability index (MVX) integrates multiple circulatory biomarkers closely linked to both metabolic and inflammatory factors. This study aims to assess MVX's potential to predict mortality in community-based population. In this large community-based prospective study, we included UK Biobank participants who underwent plasma metabolomics analysis. Gender-specific MVX scores were calculated based on six established biomarkers of mortality. Linear and non-linear associations between MVX and mortality were assessed using Cox proportional hazards models and restricted cubic spline models, respectively. Among the 274,092 UKB participants, 24,241 all-cause deaths occurred during a median follow-up period of 13.7 years. A significant, graded positive association was observed between MVX quartiles and all-cause mortality risk (<em>P</em> for trend &lt;0.05), with the highest MVX quartile exhibiting the greatest risk (HR = 1.21 and 95 % CI = 1.16–1.25 after full adjustment). Females had higher MVX score than males (<em>P</em> &lt; 0.05), but males with the same MVX score faced a greater mortality risk. Baseline age and comorbidities interacted (<em>P</em> for interaction &lt;0.05 and synergy index &gt;1) with MVX on mortality risk. Longitudinal analyses showed that females with persistently high MVX score had a significantly increased risk of mortality (HR = 1.39 in fully adjusted model). Collectively, these findings highlight MVX as a novel tool that captures metabolic and potential redox vulnerabilities in community residents, and serves as a valuable resource for identifying high-risk individuals of mortality. Further research is warranted to investigate the underlying mechanisms and establish causal relationships.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103585"},"PeriodicalIF":10.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis","authors":"Xingdou Mu ,&nbsp;Lele Feng ,&nbsp;Qiang Wang ,&nbsp;Hong Li ,&nbsp;Haitao Zhou ,&nbsp;Wei Yi ,&nbsp;Yang Sun","doi":"10.1016/j.redox.2025.103580","DOIUrl":"10.1016/j.redox.2025.103580","url":null,"abstract":"<div><div>Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P &lt; 0.01; FS%: P &lt; 0.05), hindered long-term survival (P &lt; 0.01), and intensified adverse cardiac remodeling (WGA: P &lt; 0.01; MASSON: P &lt; 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P &lt; 0.01; FS%: P &lt; 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103580"},"PeriodicalIF":10.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AGR2-mediated cell-cell communication controls the antiviral immune response by promoting the thiol oxidation of TRAF3","authors":"Mengqi Jia ,&nbsp;Xiaojing Chen ,&nbsp;Wenxue Guo ,&nbsp;Dapeng Ma ,&nbsp;Peng Wang ,&nbsp;Huanmin Niu ,&nbsp;Changhong Liu ,&nbsp;Xianjuan Lin ,&nbsp;QiQi Lu ,&nbsp;Jing Wang ,&nbsp;Xiaoxue Zheng ,&nbsp;Qi Sun ,&nbsp;Chengjiang Gao ,&nbsp;Huiqing Yuan","doi":"10.1016/j.redox.2025.103581","DOIUrl":"10.1016/j.redox.2025.103581","url":null,"abstract":"<div><div>Protein disulfide isomerases (PDIs) are essential catalysts for the formation and isomerization of disulfide bonds in diverse substrate proteins and exert multiple functions under pathophysiological conditions. Here, we show that anterior gradient 2 (AGR2), a member of PDIs, acts as a negative regulator in antiviral immunity. RNA virus infection stimulated the expression and secretion of AGR2 in epithelial cells. While AGR2 is absent in immune cells, both intracellular AGR2 and extracellular AGR2 compromised type I interferon (IFN–I) production in vitro and in vivo. The inhibitory effect of secreted AGR2 on the immune response resulted from its crosstalk with immune cells, such as macrophages, by which eAGR2 was internalized via endocytosis depending on its adhesion motif. We further identified AGR2 as a novel binding protein of TRAF3, which forms a disulfide bond between Cys81 of AGR2 and Cys296 on TRAF3. This interaction led to the inhibition of TRAF3 K63-linked ubiquitination and TRAF3-TBK1 complex formation, ultimately impairing TRAF3's ability to induce IFN-I production. The TRAF3 Cys296 mutation diminishes oxidative modification by AGR2 but enhances self-association of TRAF3 and IFN-I production. Our study demonstrated a cysteine-dependent oxidative modification of TRAF3 by AGR2 that suppresses TRAF3 activity and maintains innate immune homeostasis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103581"},"PeriodicalIF":10.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D Histology visualizing hypoxia-induced upregulation of N-terminal cysteine using de novo fluorophore generation","authors":"Yunjung Choi ,&nbsp;Joo-Yeong Jeon ,&nbsp;Jeongin Hwang ,&nbsp;Sejong Choi ,&nbsp;Ki-Myo Kim ,&nbsp;Ji-Ung Park ,&nbsp;Yan Lee","doi":"10.1016/j.redox.2025.103577","DOIUrl":"10.1016/j.redox.2025.103577","url":null,"abstract":"<div><div>Our research group developed a novel fluorescence staining strategy based on the DNFC targeting <em>N</em>-Cys in proteins. By treating biological samples with non-fluorogenic citrate and coupling reagents, we achieved strong cyan fluorescence, enabling effective visualization of <em>N</em>-Cys proteins in cells and tissues. The DNFC reaction occurs specifically on <em>N</em>-Cys residues, making it highly ideal for monitoring protein processing events, particularly within the Arg/<em>N</em>-degron pathway. Under hypoxic conditions, DNFC fluorescence is significantly enhanced, likely due to the increased presence of <em>N</em>-Cys-containing proteins. Using immunoassays and mass spectrometry, we identified Class 2 actin as a target protein under hypoxia, emphasizing the utility of 3D histopathology for analyzing actin's spatial distribution. Furthermore, we have identified a novel finding indicating a significant presence of RGS5 in red blood cells (RBCs), a discovery that has not been previously reported. Our fluorescence imaging studies, conducted across various cell types, animal tissues, and human clinical samples suggest that DNFC staining, when combined with tissue-clearing techniques, enables detailed 3D imaging of <em>N</em>-Cys proteins and may offer a means to assess molecular responses to hypoxia within tissues. This study highlights the potential of DNFC as a valuable tool for imaging and quantitative analysis of <em>N</em>-proteomes and providing a foundation for 3D histopathology in hypoxia-related disease research.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103577"},"PeriodicalIF":10.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Nicotinamide nucleotide transhydrogenase-mediated redox homeostasis promotes tumor growth and metastasis in gastric cancer” [Redox Biol. (2018) 246–255]","authors":"Shuai Li ,&nbsp;Zhuonan Zhuang ,&nbsp;Teng Wu ,&nbsp;Jie-Chun Lin ,&nbsp;Ze-Xian Liu ,&nbsp;Li-Fen Zhou ,&nbsp;Ting Dai ,&nbsp;Lei Lu ,&nbsp;Huai-Qiang Ju","doi":"10.1016/j.redox.2025.103571","DOIUrl":"10.1016/j.redox.2025.103571","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103571"},"PeriodicalIF":10.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases","authors":"Antonio Cuadrado ,&nbsp;Eduardo Cazalla ,&nbsp;Anders Bach ,&nbsp;Boushra Bathish ,&nbsp;Sharadha Dayalan Naidu ,&nbsp;Gina M. DeNicola ,&nbsp;Albena T. Dinkova-Kostova ,&nbsp;Raquel Fernández-Ginés ,&nbsp;Anna Grochot-Przeczek ,&nbsp;John D. Hayes ,&nbsp;Thomas W. Kensler ,&nbsp;Rafael León ,&nbsp;Karen T. Liby ,&nbsp;Manuela G. López ,&nbsp;Gina Manda ,&nbsp;Akshatha Kalavathi Shivakumar ,&nbsp;Henriikka Hakomäki ,&nbsp;Jessica A. Moerland ,&nbsp;Hozumi Motohashi ,&nbsp;Ana I. Rojo ,&nbsp;Anna-Liisa Levonen","doi":"10.1016/j.redox.2025.103569","DOIUrl":"10.1016/j.redox.2025.103569","url":null,"abstract":"<div><div>Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation <em>in vivo</em>.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103569"},"PeriodicalIF":10.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-driven selenium Janus single-atom nanomotors for autonomous regulating mitochondrial oxygen imbalance to catalytic therapy of rheumatoid arthritis","authors":"Xu Chen ,&nbsp;Yang Yang ,&nbsp;Jiajun Chen ,&nbsp;Yuebing He ,&nbsp;Yukai Huang ,&nbsp;Qidang Huang ,&nbsp;Weiming Deng ,&nbsp;Ruiqi Zhu ,&nbsp;Xuechan Huang ,&nbsp;Tianwang Li","doi":"10.1016/j.redox.2025.103574","DOIUrl":"10.1016/j.redox.2025.103574","url":null,"abstract":"<div><div>O₂ deficiency and excessive reactive oxygen and nitrogen species (RONS) in macrophage mitochondria is a key factor causing oxygen imbalance in rheumatoid arthritis microenvironment (RAM). Although nanocatalytic therapy that simultaneously produce O₂ and eliminate RONS offer a novel strategy for RA therapy, the therapeutic efficacy of nanozymes is limited by the lack of autonomous targeting into mitochondria. Herein, we constructed a Janus-structured nanomotor (Pd@MSe) with autonomous targeting ability by embedding Pd single-atom nanozymes into mesoporous selenium (MSe) nanozymes, and obtained a composite nanomotor (Pd@MSe-TPP) with dual-driven forces by modifying with triphenylphosphine (TPP) in MSe hemisphere. In RAM, Pd@MSe-TPP nanomotor achieved autonomously target into macrophages mitochondria with the driven of generation O₂ and TPP targeting effect, moreover under the single-atom effect of the Pd nanozymes enhanced electronic transfer between nanozymes, which significantly boosted GPx catalytic activity further effectively enhanced the diffusion of Pd@MSe-TPP nanomotor, thus quickly resorted the oxygen balance. Additionally, while regulating oxygen imbalance, Pd@MSe-TPP nanomotor enable rapidly blocked the inflammatory cascade, restored mitochondrial function and alleviated inflammation, further prevented cartilage degradation and effectively inhibited RA progression. Therefore, the exquisitely designed nanoplatform to regulation arthritic microenvironment provides a new direction for the RA therapy and the clinical translation of nanomedicine.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103574"},"PeriodicalIF":10.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary oxidized lipids in redox biology: Oxidized olive oil disrupts lipid metabolism and induces intestinal and hepatic inflammation in C57BL/6J mice","authors":"Yifan Bao ,&nbsp;Magdalena Osowiecka ,&nbsp;Christiane Ott ,&nbsp;Vasiliki Tziraki ,&nbsp;Lukas Meusburger ,&nbsp;Claudia Blaßnig ,&nbsp;Daniela Krivda ,&nbsp;Petra Pjevac ,&nbsp;Joana Séneca ,&nbsp;Matthias Strauss ,&nbsp;Christina Steffen ,&nbsp;Verena Heck ,&nbsp;Soner Aygün ,&nbsp;Kalina Duszka ,&nbsp;Kevin Doppelmayer ,&nbsp;Tilman Grune ,&nbsp;Marc Pignitter","doi":"10.1016/j.redox.2025.103575","DOIUrl":"10.1016/j.redox.2025.103575","url":null,"abstract":"<div><div>Olive oil, rich in oleic acid, is often regarded as a healthier alternative to animal fats high in saturated fatty acids and plant oils rich in oxidizable polyunsaturated fatty acids. However, the redox biological implications and health effects of oxidized olive oil (ox-OO) remain underexplored. Our study investigated its impact on lipid metabolism, intestinal and hepatic inflammation, and gut microbiota. Female C57BL/6J mice were fed either a standard normal (NFD), high-fat diet (HFD), an NFD-ox-OO or HFD-ox-OO, in which ox-OO (180 °C heating, 10 min) was the sole lipid source. Inflammation was assessed using macrophage marker F4/80 immunohistochemical (IHC) staining. Gene expression of inflammatory and lipid metabolism markers (IL-10, NF-kBp65, IL-1β, TNFα, TLR4, COX2, PPARα, PPARγ, CPT1a, SCAD, MCAD, LCAD) was analyzed by qRT-PCR. Soluble epoxide hydrolase (sEH) protein expression was measured using IHC. Oxylipin and carnitine profiles were determined by LC-MS/MS. Gut microbiota was analyzed by 16S rRNA sequencing. Ox-OO disrupted redox homeostasis, leading to lipid metabolic dysfunction in the intestines and liver. In the duodenum and proximal jejunum, ox-OO decreased the levels of anti-inflammatory oxylipins and increased pro-inflammatory mediators, leading to inflammation. In the ileum and colon, ox-OO caused lipid metabolic dysregulation and inflammation. Colon inflammation was linked to inhibited mitochondrial β-oxidation and decreased short-chain fatty acid-producing microbiomes. Notably, redox imbalances were further implicated by the identification of 9,10-epoxy-stearic acid, a novel inflammatory lipid mediator oxidized from dietary oleic acid, which upregulated sEH. Ox-OO affects lipid metabolism and may contribute to inflammation in the gut and liver, raising questions about the assumption that olive oil is always beneficial and suggesting possible risks linked to oxidized oleic acid.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103575"},"PeriodicalIF":10.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}