Journal of Cellular Physiology最新文献

{"title":"Cardiomyocytic FoxP3 Attenuates Expression of β Isoform of Myosin Heavy Chain During Cardiac Hypertrophy and Effects of Triptolide","authors":"Jia-Hui Hong,&nbsp;Xi-Chun Pan,&nbsp;Ya-Lan Xiong,&nbsp;Peng Wang,&nbsp;Yao Yuan,&nbsp;Ya Liu,&nbsp;Hai-Gang Zhang","doi":"10.1002/jcp.70026","DOIUrl":"https://doi.org/10.1002/jcp.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiac hypertrophy, a maladaptive response to chronic stress, progresses to heart failure through mechanisms requiring deeper exploration. While forkhead helix transcription factor P3 (FoxP3) is well-known as a key regulator in CD4⁺ T cells, its role in cardiomyocytes remains unclear. Here, by using isoproterenol (ISO)-induced cardiac hypertrophy models (40 mg/kg daily for in vivo study and 10 μmol/L for in vitro study), we revealed the protective role of FoxP3 in cardiac hypertrophy. Though modulating FoxP3 expression using siRNA or plasmid in cardiomyocytes, we found that FoxP3 knockdown exacerbated ISO-induced hypertrophic responses, while overexpression of FoxP3 attenuated hypertrophic effects. The protective function of cardiomyocytic FoxP3 in vivo was further confirmed by infection of adeno-associated virus. Mechanically, the cardiomyocytic FoxP3 decreased the expression of nuclear factor of activated T cells c3 (NFATc3), a key regulator of hypertrophy-related genes, to suppress hypertrophy-related genes, including atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain (β-MHC), and thus ameliorate hypertrophic responses. Besides, the immunoprecipitation and immunofluorescence determination showed that FoxP3 could interact with NFATc3 in the nucleus to form a transcription complex, thereby regulating the transcription activity of NFATc3. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs) revealed the specific binding sequences of FoxP3 in the β-MHC promoter region, with binding occupancy reduced by ISO, suggesting that FoxP3 could interact with NFATc3 to down-regulate the β-MHC expression. Importantly, we identified triptolide (TP), a bioactive natural product, as a potent inducer of FoxP3 expression. Both in vivo (10 μg/kg daily) and in vitro (10 μmol/L) studies demonstrated that TP significantly reversed cardiac hypertrophy by upregulating FoxP3 expression, thereby inhibiting NFATc3-mediated β-MHC transcription. These findings highlight cardiomyocytic FoxP3 as a novel protective factor, elucidating its underlying mechanisms and demonstrating the therapeutic potential of TP in this process.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daytime-Restricted Feeding Alleviates D-Galactose-Induced Aging in Mice and Regulates the AMPK and mTORC1 Activities","authors":"Tiepeng Li,&nbsp;Ning Huang,&nbsp;Honghan Chen,&nbsp;Yu Yang,&nbsp;Jian Zhang,&nbsp;Weitong Xu,&nbsp;Hui Gong,&nbsp;Chuhui Gong,&nbsp;Ming Yang,&nbsp;Tingting Zhao,&nbsp;Fangfang Wang,&nbsp;Hengyi Xiao","doi":"10.1002/jcp.70020","DOIUrl":"https://doi.org/10.1002/jcp.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Time-restricted feeding (TRF) is a distinct regimen of intermittent fasting advocated for health improving. Although nighttime TRF (NRF) in rodents is analogous to daytime TRF (DRF) in humans and has health benefits, the effects of DRF on rodent's health remain uncertain. The adverse health effects of DRF in rodents are primarily attributed to its implementation-induced temporal shift in the expression of circadian rhythm-related genes. However, studies also demonstrate the health–beneficial effect of restricted feeding itself on metabolic homeostasis, particularly in periphery tissues. Moreover, the direct effects of DRF on aging progression in rodents are underexplored, highlighting a gap in current research. To explore the overall health effects of long-term DRF in rodents, especially its influence on aging progression, we investigated the impact of long-term DRF on mice under a progeric aging condition. Results showed that both 4-h and 8-h DRF regimens exerted positive effects on aging retardation; these effects were manifested as improved physical and memory capacities, enhanced liver and kidney functions, and reduced oxidative damage and inflammatory response. These DRF regimens also lowered the manifestation of aging-related markers in peripheral tissues, with decreased SA-β-gal staining and p16 expression. Mechanistically, DRF regimens, especially DRF8, upregulated AMPK signaling and downregulated mTORC1 signaling. Interestingly, the health benefits of DRF are similar to those of metformin intervention. In conclusion, our study demonstrates for the first time that DRF effectively counteracts oxidative stress-induced aging progression in mice, supporting the viewpoint that TRF as a promising strategy for preventing aging and aging-related disorders.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The Effects and Mechanisms of Myeloid Differentiation Protein 2 on Intestinal Mucosal Permeability in Mice With Chronic Colitis”","authors":"","doi":"10.1002/jcp.70009","DOIUrl":"https://doi.org/10.1002/jcp.70009","url":null,"abstract":"<p>Han C., Q. Guan, L. Guo, Y. Yang, S. Ruan, and X. Zhang. 2019. “The Effects and Mechanisms of Myeloid Differentiation Protein 2 on Intestinal Mucosal Permeability in Mice With Chronic Colitis.” <i>Journal of Cellular Physiology</i> 234, no. 11: 21089–21099. https://doi.org/10.1002/jcp.28711.</p><p>In the initial version of the proof stage, We mistakenly inserted incorrect panels in Figure 2d, Figure 3a, Figure 4d, Figure 5a, and Figure 6c. Specifically:</p><p>Figure 2c: We have confused the panels of Con and DSS, and the magnification is not consistent. We will present the correct results as follows:</p><p>Figure 3a: Strip insertion error for MD2. We will present the correct results as follows:</p><p>Figure 4d: TLR4 strip insertion error. We will present the correct results as follows:</p><p>Figure 5a: MD2 and GAPDH strip insertion error. We will present the correct results as follows:</p><p>Figure 6c: GAPDH strip insertion error. We will present the correct results as follows:</p><p>This correction doesn't change the results and conclusions. The authors apologize for any confusion these errors may have caused.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Single-Cell Analysis Reveals Tendon Progenitor Dysfunction by Age-Associated Oxidative Stress and Its Restoration by Antioxidant Treatments","authors":"Youngjae Jeong,&nbsp;Dongwook Yang,&nbsp;Jea Giezl Solidum,&nbsp;Laura Ortinau,&nbsp;Dongsu Park","doi":"10.1002/jcp.70016","DOIUrl":"https://doi.org/10.1002/jcp.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/progenitor cells (TSPCs) remain unknown. Here, comparative single cell transcriptomics of early postnatal (2 weeks old) and adult (20 weeks old) mouse tendons revealed that adult tendons have reduced number of TSPCs, decreased gene expression in tendon and cartilage development, and a greater population of fibro-tenogenic cells. Notably, adult TSPCs and tenocytes exhibit increased expression of immune-response and oxidative-stress genes with higher EGFR but decreased IGF signaling. Adult tendon cells show increased levels of intracellular reactive oxygen species (ROS) in vivo. In contrast, antioxidant treatment of adult tendons significantly reduces intracellular ROS of TSPCs and improves tendon strength in vivo. Hence, these findings suggest that increased inflammation and ROS during tendon aging deteriorates tendon function and regeneration that can be mitigated by antioxidant treatment.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trophic Factors in Muscle-Nerve Cross-Talk Signaling Augment Muscle Fiber and Motor Endplate Development","authors":"James T. Redden,&nbsp;Sophie Kothe,&nbsp;David J. Cohen,&nbsp;Zvi Schwartz,&nbsp;Michael J. McClure","doi":"10.1002/jcp.70013","DOIUrl":"https://doi.org/10.1002/jcp.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>Synaptogenesis requires complex coordination between the terminating motor neuron and the developing myofiber endplate. Cross-talk research has focused on in vivo models or singular treatments with known signaling molecules identified from these animal studies. However, in vivo models are inefficient at measuring dynamic signaling changes due to assay resolution and cost. Further, despite advances in culture methods relying on microfluidic platforms, much remains unknown about the dynamic cross-talk between these two key cell types. As such, there is an unmet investigation into simple and reproducible coculture studies. In this study, we characterize both myoblast (C2C12) and motor neuron (NSC-34) changes that occur in either a conditioned media model, a transwell coculture, and a 2D migration coculture. We successfully demonstrate repeatable changes in synaptogenesis with ~38% increase in Chrng protein levels (<i>p</i> &lt; 0.05) in each model, increased myotube alignment in cocultured myoblasts measured with FFT analysis, and show motor neurons are preferentially chemo-attracted to myotubes without the use of neurite-path constraining microfluidics. Lastly, we identified a potential new signaling protein responsible for motor endplate development, apolipoprotein E (ApoE). This coculture approach reveals changes to myotube myogenesis and synaptogenesis providing a consistent platform for cross-talk and pathway analysis for future studies.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Metabolic Sensor GPR81/HCAR1 in Diabetic Podocytes: Downregulated Lipolysis Results in the Deterioration of Glomerular Filtration Barrier","authors":"Klaudia Grochowalska,&nbsp;Maria Szrejder,&nbsp;Patrycja Rachubik,&nbsp;Irena Audzeyenka,&nbsp;Dorota Rogacka,&nbsp;Magdalena Narajczyk,&nbsp;Agnieszka Piwkowska","doi":"10.1002/jcp.70014","DOIUrl":"https://doi.org/10.1002/jcp.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>The effacement of podocyte foot processes, which form slit diaphragms, are common features of proteinuria. Exploring podocyte energy metabolism, especially under diabetic conditions, may offer insights into the pathogenesis of diabetic kidney disease. Lipid accumulation is recognized as a cause of podocyte cytoskeleton remodeling and insulin resistance. Thus, the role of the metabolic sensor G-protein-coupled receptor 81 (GPR81) was examined in the molecular pathway of lipid accumulation in podocytes under hyperglycemic conditions. It was discovered that hyperglycemia downregulated the cyclic adenosine monophosphate/protein kinase A signaling pathway, which downregulated the expression of adipose triglyceride lipase (ATGL). Perilipin 1 was also downregulated; simultaneously, lipid droplet accumulation was enhanced. Glycerol and free fatty acid concentrations were also reduced, providing evidence of lipolysis inhibition. Interestingly, the expression of GPR81 decreased under hyperglycemia conditions despite the evidence of its activation, indicating strict lipolysis regulation. More importantly, cell functions were altered, reflected by an increase in albumin permeability and rearrangement of the actin cytoskeleton. The effect of ATGL activity inhibition on lipolysis, actin cytoskeleton arrangement, and permeability of the podocyte monolayer was investigated. The results were similar to GPR81 downregulation. Altogether, the present data indicate that GPR81 is likely a crucial part of the lipid sensing system, and its alterations during hyperglycemia might contribute to glomerular filtration barrier deterioration in diabetic kidney disease.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptome Decoding Umbilical Cord-Derived Mesenchymal Stem Cell Heterogeneity Reveals a Unique IL1R1HighPDGFRAHigh Ultroser-G-MSC With Osteogenesis and Chondrogenesis Signatures","authors":"Shihao Huang,&nbsp;Xinyu Xu,&nbsp;Jiaqi Guo,&nbsp;Zhuolan Li,&nbsp;Yanlin Wu,&nbsp;Yuanyuan Liu,&nbsp;Qinyi Sun,&nbsp;Sihan Wang,&nbsp;Huilin Yan,&nbsp;Yueyan Su,&nbsp;Wei Guo","doi":"10.1002/jcp.70004","DOIUrl":"https://doi.org/10.1002/jcp.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>The heterogeneity of human umbilical cord mesenchymal stem cells (hUC-MSCs) is culturing-dependent, resulting in functional non-uniformness. To achieve the best clinical benefit, a comprehensive understanding of the origin of the heterogeneity in different culture systems can identify functional subgroups to direct the precise application of hUC-MSCs. Here, we create a single-cell transcriptome atlas of hUC-MSC in different culture systems for the identification of a subgroup of Ultroser-G-MSCs with high osteogenic and chondrogenic potentials featured by high expressions of IL1R1 and PDGFRA. Further experimental validations surprisingly reveal that IL1R1^highPDGFRA^high Ultroser-G-MSCs possess advantages over “traditional” hUC-MSCs in the treatments of modeled osteoarthritis, leading to a cell-cell communication network centered in Clusters 0 and 2. Moreover, we found that Wnt5 signaling is the key pathway for the dynamic transformation of osteogenic and chondrogenic phenotypes in hUC-MSC. Overall, the present study paves the way for the clarification of heterogenetic nature of hUC-MSC in different culture systems for the selection of optimal MSC types to achieve the precision on clinical treatments.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stearoyl-CoA Desaturase 1 Regulates Metabolism and Inflammation in Mouse Perivascular Adipose Tissue in Response to a High-Fat Diet","authors":"Adrian Sowka,&nbsp;Volodymyr V. Balatskyi,&nbsp;Viktor O. Navrulin,&nbsp;James M. Ntambi,&nbsp;Pawel Dobrzyn","doi":"10.1002/jcp.31510","DOIUrl":"https://doi.org/10.1002/jcp.31510","url":null,"abstract":"<div>\u0000 \u0000 <p>The dysregulation of perivascular adipose tissue (PVAT) is a key contributor to obesity-induced vascular dysfunction. Mouse periaortic adipose tissue is divided into two parts: thoracic perivascular adipose tissue (TPVAT) and abdominal perivascular adipose tissue (APVAT). These two parts have different physiological properties, which translate into different effects on the vascular wall in the onset of metabolic syndrome. Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that is involved in the synthesis of monounsaturated fatty acids and has been shown to play an important role in metabolic syndrome, including vascular homeostasis. Despite a considerable focus on the role of SCD1 in the development of vascular disorders, there is currently a lack of knowledge of the relationship between SCD1 and PVAT. The present study investigated effects of SCD1 deficiency on lipolysis, β-oxidation, mitochondrial dynamics, and inflammation in mouse TPVAT and APVAT under high-fat diet (HFD) feeding conditions. We found lower triglyceride levels in PVAT in SCD1^−/− mice both in vitro and in vivo compared with wildtype perivascular adipocytes, attributable to activated lipolysis and β-oxidation. Moreover, PVAT in HFD-fed SCD1^−/− mice was characterized by higher levels of oxidative phosphorylation complexes and mitochondrial respiratory potential and alterations of mitochondrial morphology compared with wildtype mice. Furthermore, TPVAT and APVAT in SCD1^−/− mice showed signs of greater pro-inflammatory macrophage polarization and higher inflammatory markers that were induced by a HFD. This may be related to the accumulation free fatty acids and diacylglycerols, which are enriched in saturated fatty acids. These findings elucidate the role of SCD1 in maintaining vascular integrity.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Effects of Photoperiod on Morphology and Function in Testis and Epididymis of Cricetulus Barabensis”","authors":"","doi":"10.1002/jcp.70010","DOIUrl":"https://doi.org/10.1002/jcp.70010","url":null,"abstract":"<p>J. Mou, J. Xu, Z. Wang, C. Wang, X. Yang, X. Wang, H. Xue, M. Wu, and L. Xu, “Effects of Photoperiod on Morphology and Function in Testis and Epididymis of <i>Cricetulus Barabensis</i>,” <i>Journal of Cellular Physiology</i> 236, no. 3 (2021): 2109-2125, https://doi.org/10.1002/jcp.29998.</p><p>In the published article, the authors made two inadvertent mistakes in Figure 7: 1) In Figure 7a, the LD-merged pictures were wrongly copied to the corresponding position of the SD-merged ones. 2) In Figure 7b, the panel of the SD group was incorrectly placed at the corresponding position of the LD group. The corrected Figure 7 is presented below.</p><p>The authors apologize for this error and for the inconvenience it may have caused.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias","authors":"Pegah Bahrami,&nbsp;Kelly A. Aromolaran,&nbsp;Ademuyiwa S. Aromolaran","doi":"10.1002/jcp.70012","DOIUrl":"https://doi.org/10.1002/jcp.70012","url":null,"abstract":"<p>The prevalence of obesity and associated metabolic disorders such as diabetes is rapidly increasing; therefore, concerns regarding their cardiovascular consequences, including cardiac arrhythmias, are rising. As obesity progresses, the excessively produced lipids accumulate in unconventional areas such as the epicardial adipose tissue (EAT) around the myocardium. Metabolic alterations in obesity contribute to the transformation of these ectopic fat deposits into arrhythmogenic substrates. However, despite advances in therapeutic approaches, particularly in lowering EAT volume and thickness through sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, obese and diabetic patients still suffer from fatal arrhythmias that may lead to sudden cardiac death. Therefore, an investigation into how unappreciated underlying pathways such as lipid mediators contribute to the transformation of adipose tissues into proinflammatory and arrhythmogenic substrates is of significance. Leukotriene B4 (LTB4) is an eicosanoid derived from arachidonic acid and acts as a lipid mediator. LTB4 has recently been identified to be associated with cardiac ion channel modulations and arrhythmogenic conditions in diabetes. LTB4 increases circulatory free fatty acids (FFAs) and has been associated with adipocyte hypertrophy. LTB4 also interferes with insulin signaling pathways, instigating insulin resistance (IR). In addition, LTB4, as a potent chemoattractant, contributes to the mobilization of circulatory immune cells such as monocytes and promotes inflammatory macrophage polarization and macrophage dysfunction. Thus, this review provides a comprehensive overview of LTB4's underlying pathways in obesity; illustrates how these pathways might lead to alterations in cardiac ion channels, currents, and cardiac arrhythmias; and shows how they might pose a therapeutic target for metabolic-associated arrhythmias.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}