{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:19:58Z","timestamp":1792030798387,"version":"4.4.0"},"reference-count":279,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Research and Innovation program under the Marie Sk\u0142odowska-Curie","award":["722619 (FOIE GRAS)"],"award-info":[{"award-number":["722619 (FOIE GRAS)"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation program under the Marie Sk\u0142odowska-Curie","award":["734719 (mtFOIE GRAS)"],"award-info":[{"award-number":["734719 (mtFOIE GRAS)"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation program under the Marie Sk\u0142odowska-Curie","award":["CUP H99C20000340002 (Fever Apulia)"],"award-info":[{"award-number":["CUP H99C20000340002 (Fever Apulia)"]}]},{"name":"Regione Puglia","award":["722619 (FOIE GRAS)"],"award-info":[{"award-number":["722619 (FOIE GRAS)"]}]},{"name":"Regione Puglia","award":["734719 (mtFOIE GRAS)"],"award-info":[{"award-number":["734719 (mtFOIE GRAS)"]}]},{"name":"Regione Puglia","award":["CUP H99C20000340002 (Fever Apulia)"],"award-info":[{"award-number":["CUP H99C20000340002 (Fever Apulia)"]}]},{"name":"University of Bari Aldo Moro","award":["722619 (FOIE GRAS)"],"award-info":[{"award-number":["722619 (FOIE GRAS)"]}]},{"name":"University of Bari Aldo Moro","award":["734719 (mtFOIE GRAS)"],"award-info":[{"award-number":["734719 (mtFOIE GRAS)"]}]},{"name":"University of Bari Aldo Moro","award":["CUP H99C20000340002 (Fever Apulia)"],"award-info":[{"award-number":["CUP H99C20000340002 (Fever Apulia)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4\/\u03b2-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.<\/jats:p>","DOI":"10.3390\/nu14234950","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T08:27:29Z","timestamp":1669105649000},"page":"4950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-7376","authenticated-orcid":false,"given":"Agostino","family":"Di Ciaula","sequence":"first","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Biomedical Sciences & Human Oncology, University of Bari \u201cAldo Moro\u201d Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonilde","family":"Bonfrate","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Biomedical Sciences & Human Oncology, University of Bari \u201cAldo Moro\u201d Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-8987","authenticated-orcid":false,"given":"Jacek","family":"Baj","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5943-9531","authenticated-orcid":false,"given":"Mohamad","family":"Khalil","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Biomedical Sciences & Human Oncology, University of Bari \u201cAldo Moro\u201d Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Garruti","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari \u201cAldo Moro\u201d Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Stellaard","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, Venusberg-Campus 1, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-7651","authenticated-orcid":false,"given":"David Q.-H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. 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