{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:00:11Z","timestamp":1790312411442,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"\n Introduction<\/jats:title>\n \n The\n CEL<\/jats:italic>\n gene encodes the pancreatic enzyme carboxyl ester lipase. The human\n CEL-HYB1<\/jats:italic>\n allele, a hybrid variant of\n CEL<\/jats:italic>\n and its adjacent pseudogene\n CELP<\/jats:italic>\n , is associated with a five-fold increased risk for chronic pancreatitis in European cohorts. Humanized\n Cel-HYB1<\/jats:italic>\n mice develop chronic pancreatitis spontaneously albeit with a relatively mild presentation. The aim of this study was to further characterize the pancreatic phenotype in\n Cel-HYB1<\/jats:italic>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated\n Cel-HYB1<\/jats:italic>\n animals by two complementary approaches. First, we analyzed compound heterozygous\n Cel-16R\/HYB1<\/jats:italic>\n mice where the second\n Cel<\/jats:italic>\n allele carries the 16-repeat (\n 16R<\/jats:italic>\n ) VNTR of the normal human\n CEL<\/jats:italic>\n gene. Second, heterozygous and homozygous\n Cel-HYB1<\/jats:italic>\n animals were fed either a high-fat diet or standard chow for 3 months. All animals were characterized with respect to growth, organ weights, pancreas pathology and glucose metabolism.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the\n Cel-16R\/HYB1<\/jats:italic>\n model, body weight, pancreas weight and pancreatic histology were comparable to those of heterozygous\n Cel-HYB1<\/jats:italic>\n mice. However, within each genotype female mice generally exhibited more pronounced pancreatic histopathological changes than males. Male\n Cel-16R\/HYB1<\/jats:italic>\n mice had larger fat depots at 6 months of age, and\n Cel-16R\/HYB1<\/jats:italic>\n animals of both sexes showed slightly improved glucose tolerance relative to heterozygous\n Cel-HYB1<\/jats:italic>\n mice. When fed a high-fat diet, increased body weights were seen across all mouse groups without genotype-dependent differences. Under this condition,\n Cel-HYB1<\/jats:italic>\n animals displayed more pronounced pancreatic histopathology than littermate controls. Notably, no consistent genotype-dependent differences in glucose tolerance were observed in\n Cel-HYB1<\/jats:italic>\n mice under either high-fat diet or standard chow conditions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The humanized\n Cel-16R<\/jats:italic>\n allele did not substantially modify the pancreatic phenotype of\n Cel-HYB1<\/jats:italic>\n mice, although\n Cel-16R\/HYB1<\/jats:italic>\n animals exhibited somewhat improved glucose tolerance compared with heterozygous\n Cel-HYB1<\/jats:italic>\n mice. In contrast, high-fat diet promoted exocrine pancreatic pathology, supporting a role for dietary factors as potential modifiers of disease severity in\n CEL-HYB1<\/jats:italic>\n -associated chronic pancreatitis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphys.2026.1924024","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:28:00Z","timestamp":1790310480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High-fat diet accelerates pancreas pathology in the Cel-HYB1 mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Ranveig S.","family":"Brekke","sequence":"first","affiliation":[{"name":"Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Gravdal","sequence":"additional","affiliation":[{"name":"Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate V.","family":"Seierstad","sequence":"additional","affiliation":[{"name":"Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunjun K.","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine","place":["St. Louis, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine","place":["St. Louis, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline S.","family":"Verbeke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oslo University Hospital Rikshospitalet","place":["Oslo, Norway"]},{"name":"Department of Pathology, Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente B.","family":"Johansson","sequence":"additional","affiliation":[{"name":"Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Molven","sequence":"additional","affiliation":[{"name":"Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]},{"name":"Department of Pathology and Section for Cancer Genomics, Haukeland University Hospital","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karianne","family":"Fjeld","sequence":"additional","affiliation":[{"name":"Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen","place":["Bergen, Norway"]},{"name":"Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen","place":["Bergen, Norway"]},{"name":"Department of Medical Genetics, Haukeland University Hospital","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"30965","DOI":"10.1038\/s41598-024-82077-4","article-title":"Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis","volume":"14","author":"Berke","year":"2024","journal-title":"Sci. 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