{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:19:36Z","timestamp":1792030776667,"version":"4.4.0"},"reference-count":178,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["20K22746"],"award-info":[{"award-number":["20K22746"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor \u03b1 (RXR\u03b1), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR\/RXR\u03b1 heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15\/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-\u03b2-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15\/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases.<\/jats:p>","DOI":"10.3390\/ijms23116046","type":"journal-article","created":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T01:40:45Z","timestamp":1653702045000},"page":"6046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":197,"title":["Molecular Basis of Bile Acid-FXR-FGF15\/19 Signaling Axis"],"prefix":"10.3390","volume":"23","author":[{"given":"Takeshi","family":"Katafuchi","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Department of Biomedical Science, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-905X","authenticated-orcid":false,"given":"Makoto","family":"Makishima","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Biomedical Science, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.biochem.72.121801.161712","article-title":"The enzymes, regulation, and genetics of bile acid synthesis","volume":"72","author":"Russell","year":"2003","journal-title":"Annu. 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