{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:01:33Z","timestamp":1784818893519,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["GK20250096"],"award-info":[{"award-number":["GK20250096"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolic syndrome (MetS) has been associated with increased acute pancreatitis (AP) severity. This study aimed to identify shared differentially expressed genes (CDEGs) between MetS and AP and to prioritize mechanistically relevant targets. The shared genetic basis and causal effect of MetS on AP were first assessed using linkage disequilibrium score regression (LDSC) and two\u2010sample Mendelian randomization (MR). Public Gene Expression Omnibus (GEO) datasets were analyzed to define shared CDEGs. A multi\u2010step pipeline incorporating functional enrichment, protein\u2013protein interaction (PPI) analysis, and transcription factor mapping was used to identify AP hub genes (AP\u2010HGs). Functional relatedness and putative causal relationships were evaluated using GeneMANIA, MR, and single\u2010cell RNA sequencing (scRNA\u2010seq). Finally, computational drug prediction and molecular docking were performed to identify potential therapeutic agents. Key findings were further validated in a hyperlipidemia AP (HAP) model. A positive genetic correlation between MetS and AP was identified by LDSC, and MR supported a causal effect of MetS on increased AP risk. BCAT1, GPAT3, ANP32C, and ZNF683 were identified as CDEGs between MetS and AP. MAPK14 was identified as a central AP\u2010HG. MAPK14, BCAT1, and GPAT3 were effective predictors for severe AP (SAP), with AUCs of 0.738, 0.722, and 0.744, respectively. GeneMANIA predicted a high degree of physical interaction (77.6%) among these genes. MR analysis provided supportive genetic evidence linking MAPK14 expression to inflammatory mediators including IL\u20101ra and TNFR\u20101. scRNA\u2010seq analysis in an experimental AP model localized Mapk14 expression predominantly to macrophages, while Bcat1 marked a unique, proliferative fibroblast subpopulation that emerged transiently during inflammation and exhibited an anabolic metabolic signature. Ozagrel was prioritized as an exploratory candidate with favorable predicted binding affinities and requires further validation. In a HAP model, aggravated pancreatic injury and upregulation of BCAT1 and MAPK14 were confirmed under the high\u2010fat background. A genetic and transcriptomic link between MetS and AP was identified. MAPK14\u2010associated inflammation and Bcat1\u2010positive fibroblast remodeling may contribute to AP aggravation under metabolic disturbance. These findings provide candidate biomarkers for SAP prediction and support BCAT1 and MAPK14 as potential mechanistic targets.<\/jats:p>","DOI":"10.1096\/fj.202601080rr","type":"journal-article","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T17:02:04Z","timestamp":1783270924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared Genetic Risk Between Acute Pancreatitis and Metabolic Syndrome Converges on a BCAT1\u2010Positive Fibroblast Subpopulation and MAPK14\u2010Driven Inflammation"],"prefix":"10.1096","volume":"40","author":[{"given":"Xiaoying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxin","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarrin","family":"Basharat","sequence":"additional","affiliation":[{"name":"Alpha Genomics (Private) Limited  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Zippi","sequence":"additional","affiliation":[{"name":"Unit of Gastroenterology and Digestive Endoscopy Sandro Pertini Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirio","family":"Fiorino","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine Budrio Hospital, Local Health Unit of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6857-4252","authenticated-orcid":false,"given":"Wandong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31310-6"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0158-2"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-05928-5"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.05.007"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.001180"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.19.2486"},{"issue":"1","key":"e_1_2_14_9_1","first-page":"86","article-title":"Impact of Metabolic Comorbidities on Outcomes of Patients With Acute Pancreatitis: A Scoping Review","volume":"58","author":"Goodger R. 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