{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:33:49Z","timestamp":1793644429599,"version":"4.5.1"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The farnesoid X receptor (FXR) is an attractive pharmaceutical target for metabolic dysfunction\u2010associated steatotic liver disease (MASLD). However, its tissue\u2010specific roles in energy metabolism remain controversial, hindering the development of effective therapies. To address this, new approaches are required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A novel mouse model was developed to facilitate the re\u2010expression of endogenous FXR in specific tissues on a global FXR\u2010null background. Liver\u2010specific and gut\u2010specific FXR re\u2010expression models were generated. Mice were subjected to a high\u2010fat diet (HFD) for 12\u2009weeks, after which metabolic indices, bile acid (BA) profiles, and gut microbiota composition were analysed. Antibiotic treatment was used to mimic germ\u2010free conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The resistance of FXR\u2010null mice to MASLD and most HFD\u2010induced metabolic disorders, including increased body weight, adiposity, hepatic triglyceride (TG) accumulation, and hyperglycemia, was reversed by liver, but not gut, FXR re\u2010expression. Gut FXR re\u2010expression restored the increased intestinal TG absorption in FXR\u2010null mice by limiting 12OH BA synthesis and inhibiting intestinal microsomal triglyceride transfer protein (MTTP). Moreover, gut FXR activity was essential for gut microbiota\u2010driven promotion of diet\u2010induced obesity (DIO) and MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study overcomes the limitations of traditional tissue\u2010specific knockout models, providing a more comprehensive understanding of FXR's complex roles in metabolic homeostasis, encouraging the development of organ\u2010specific FXR targeting strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70027","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:30:03Z","timestamp":1741714203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Disentangling Organ\u2010Specific Roles of Farnesoid X Receptor in Bile Acid and Glucolipid Metabolism"],"prefix":"10.1111","volume":"45","author":[{"given":"Tingting","family":"Li","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Clinical Research Center for Metabolic Diseases, Shanghai National Center for Translational Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Key Laboratory for Endocrine and 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