Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization
Abstract Acute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85354-y |
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| author | Wenbin Liu Song Yang Yuhan Li Dava Tenzing Ruizi Shi Yang Jiang Hao Deng Enqiang Mao Ying Chen Yihui Wang |
| author_facet | Wenbin Liu Song Yang Yuhan Li Dava Tenzing Ruizi Shi Yang Jiang Hao Deng Enqiang Mao Ying Chen Yihui Wang |
| author_sort | Wenbin Liu |
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| description | Abstract Acute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration of genetic variants across the genome in a study population of 10,630 AP cases and 844,679 non-AP individuals revealed multiple lipidome entities significantly associated with AP risk. The study identified 23 lipid species with unidirectional causal effects on AP after accounting for heterogeneity, pleiotropy, and potential reverse causation. Additionally, five inflammatory factors (CD5, IL-13, MMP-1, STAMBP, TNFRSF9) showed significant potential causal relationship with AP. Further analysis elucidated the intricate interplay between specific lipid species and inflammatory mediators in influencing AP incidence. Notably, Sterol ester (27:1/20:4) and several phosphatidylcholine species, including PC (17:0_20:4), PC (18:0_20:4), PC (18:0_20:5), and PC (O-18:2_20:4), were negatively associated with AP risk. This protective effect was partially mediated through decreased levels of inflammatory markers, particularly STAMBP and MMP-1. The study found that these phosphatidylcholines and sterol esters significantly reduced the levels of these pro-inflammatory factors, thereby potentially mitigating AP risk. Conversely, Phosphatidylinositol (16:0_18:1) demonstrated a positive association with AP risk. This detrimental effect was partially mediated by increased levels of MMP-1 and STAMBP, suggesting a pro-inflammatory mechanism. The study provides evidence that this specific phosphatidylinositol species may exacerbate AP risk by promoting inflammatory pathways. These findings elucidate the complex interplay between lipid metabolites, inflammation, and AP pathogenesis, potentially informing novel therapeutic strategies. The study highlights the utility of Mendelian randomization in uncovering potential causal relationship in AP. It underscores the requirement for further study into the molecular mechanisms underlying lipid-mediated inflammation in AP, particularly the roles of phosphatidylcholines and sterol esters in modulating inflammatory responses. Further studies are warranted to confirm our observations in laboratory models and assess their translational value in developing AP preventive and therapeutic strategies. |
| format | Article |
| id | doaj-art-220bd914a3b148999a16b073bbab5bbd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-220bd914a3b148999a16b073bbab5bbd2025-01-12T12:14:41ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85354-yExploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomizationWenbin Liu0Song Yang1Yuhan Li2Dava Tenzing3Ruizi Shi4Yang Jiang5Hao Deng6Enqiang Mao7Ying Chen8Yihui Wang9Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineThe Second School of Clinical Medicine, Southern Medical UniversityDepartment of Emergency, People’s Hospital of Shigatse CityShanghai Institute of Aviation Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Acute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration of genetic variants across the genome in a study population of 10,630 AP cases and 844,679 non-AP individuals revealed multiple lipidome entities significantly associated with AP risk. The study identified 23 lipid species with unidirectional causal effects on AP after accounting for heterogeneity, pleiotropy, and potential reverse causation. Additionally, five inflammatory factors (CD5, IL-13, MMP-1, STAMBP, TNFRSF9) showed significant potential causal relationship with AP. Further analysis elucidated the intricate interplay between specific lipid species and inflammatory mediators in influencing AP incidence. Notably, Sterol ester (27:1/20:4) and several phosphatidylcholine species, including PC (17:0_20:4), PC (18:0_20:4), PC (18:0_20:5), and PC (O-18:2_20:4), were negatively associated with AP risk. This protective effect was partially mediated through decreased levels of inflammatory markers, particularly STAMBP and MMP-1. The study found that these phosphatidylcholines and sterol esters significantly reduced the levels of these pro-inflammatory factors, thereby potentially mitigating AP risk. Conversely, Phosphatidylinositol (16:0_18:1) demonstrated a positive association with AP risk. This detrimental effect was partially mediated by increased levels of MMP-1 and STAMBP, suggesting a pro-inflammatory mechanism. The study provides evidence that this specific phosphatidylinositol species may exacerbate AP risk by promoting inflammatory pathways. These findings elucidate the complex interplay between lipid metabolites, inflammation, and AP pathogenesis, potentially informing novel therapeutic strategies. The study highlights the utility of Mendelian randomization in uncovering potential causal relationship in AP. It underscores the requirement for further study into the molecular mechanisms underlying lipid-mediated inflammation in AP, particularly the roles of phosphatidylcholines and sterol esters in modulating inflammatory responses. Further studies are warranted to confirm our observations in laboratory models and assess their translational value in developing AP preventive and therapeutic strategies.https://doi.org/10.1038/s41598-025-85354-yAcute pancreatitisLipidomeInflammatory factorsMendelian randomization |
| spellingShingle | Wenbin Liu Song Yang Yuhan Li Dava Tenzing Ruizi Shi Yang Jiang Hao Deng Enqiang Mao Ying Chen Yihui Wang Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization Scientific Reports Acute pancreatitis Lipidome Inflammatory factors Mendelian randomization |
| title | Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| title_full | Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| title_fullStr | Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| title_full_unstemmed | Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| title_short | Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| title_sort | exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization |
| topic | Acute pancreatitis Lipidome Inflammatory factors Mendelian randomization |
| url | https://doi.org/10.1038/s41598-025-85354-y |
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