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Herein, we report a pivotal role of farnesoid X receptor (FXR) signaling and fatty acid oxidation (FAO) in PN\u2010induced villus atrophy. A total of 14 pediatric SBS patients receiving PN were enrolled in this study. Those patients with IF showed longer PN duration and significant intestinal villus atrophy, characterized by remarkably increased enterocyte apoptosis concomitant with impaired FXR signaling and decreased FAO genes including carnitine palmitoyltransferase 1a (CPT1a). Likewise, similar changes were found in an in vivo model of neonatal Bama piglets receiving 14\u2010day PN, including villus atrophy and particularly disturbed FAO process responding to impaired FXR signaling. Finally, in order to consolidate the role of the FXR\u2010CPT1a axis in modulating enterocyte apoptosis, patient\u2010derived organoids (PDOs) were used as a mini\u2010gut model in vitro\n                    <jats:italic>.<\/jats:italic>\n                    Consequently, pharmacological inhibition of FXR by tauro\u2010\u03b2\u2010muricholic acid (T\u2010\u03b2MCA) evidently suppressed CPT1a expression leading to reduced mitochondrial FAO function and inducible apoptosis. In conclusion, impaired FXR\/CPT1a axis and disturbed FAO may play a pivotal role in PN\u2010induced villus atrophy, contributing to intestinal failure in SBS patients.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201527r","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T10:21:22Z","timestamp":1671099682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impaired\n                    <scp>FXR\u2010CPT1a<\/scp>\n                    signaling contributes to parenteral nutrition\u2010induced villus atrophy in short\u2010bowel syndrome"],"prefix":"10.1096","volume":"37","author":[{"given":"Yuling","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai 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