{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:52:34Z","timestamp":1780372354325,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Maternal obesity increases the risk of the paediatric form of metabolic dysfunction\u2010associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a Japanese macaque model, we investigated the impact of maternal Western\u2010style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third\u2010trimester fetuses and 3\u2010year\u2010old juvenile offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Juveniles exposed to mWSD had increased hepatic collagen I\/III content and stellate cell activation in portal regions. mWSD increased transcriptional signatures of FXR activation, while pwWSD impaired FXR pathway genes and increased liver BA content. Both mWSD and pwWSD increased serum BA concentrations. Notably, mWSD\u2010exposed juvenile offspring had increased periportal CK19 expression and cholangiocyte gene expression supporting proliferation compared with maternal chow\u2010exposed offspring. Fetuses exposed to mWSD had increased CK19 expression and hepatic BAs which correlated positively with periportal collagen deposition and negatively with markers of fetal oxygenation. In juvenile offspring, increased serum BAs correlated positively with hepatic oxidative stress and portal fibrosis without elevated liver enzymes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>mWSD is associated with hallmarks of paediatric MASLD including portal bile ductular reaction, portal fibrosis and dysregulated BA homeostasis. These conditions begin in utero and persist in juvenile offspring regardless of their postweaning diet. These findings implicate changes in BA metabolism that may drive developmental programming of MASLD in juvenile offspring beginning in utero.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16236","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T07:55:31Z","timestamp":1737791731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4390-4531","authenticated-orcid":false,"given":"Michael J.","family":"Nash","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Dobrinskikh","sequence":"additional","affiliation":[{"name":"Department 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