Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 19.
doi: 10.1097/HEP.0000000000001539. Online ahead of print.

Bile acid signaling in MASLD: From pathogenesis to therapeutic applications

Benedikt Simbrunner  1 , Rafael Paternostro, Thomas Reiberger, Michael Trauner
Affiliations

Bile acid signaling in MASLD: From pathogenesis to therapeutic applications

Benedikt Simbrunner et al. Hepatology. .

Abstract

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) causes considerable global morbidity and mortality. Dysregulated lipid and glucose metabolism are central elements in the pathogenesis of MASLD by promoting hepatocellular stress, inflammation, and liver fibrosis that may culminate in the development of cirrhosis and liver cancer. Moreover, intestinal dysbiosis and bacterial translocation trigger hepatic and systemic inflammation, further contributing to the pathogenesis and progression of MASLD. Bile acid (BA) receptors regulate hepatic metabolism and gut integrity as central players in the pathophysiology of MASLD. Therapeutic strategies targeting these BA receptors along the gut-liver axis, either directly through agonists or indirectly via modulation of BA transport, are currently within the focus of clinical research. This review summarizes mechanistic aspects of BA signaling in MASLD, key evidence of experimental and clinical studies on BA receptor agonists, and provides an outlook for future opportunities and challenges on the road to the implementation of novel therapies targeting BA receptors and BA signaling in MASLD.

Keywords: FGF19; FXR; GLP-1; MASH; NAFLD; NASH; TGR5; fibrosis; inflammation; metabolism.

PubMed Disclaimer

References

    1. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78:1966–1986.
    1. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.
    1. Younossi ZM, Marchesini G, Pinto-Cortez H, Petta S. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Implications for liver transplantation. Transplantation. 2019;103:22–27.
    1. Younossi ZM, Stepanova M, Ong J, Trimble G, AlQahtani S, Younossi I, et al. Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19:580–589.e5.
    1. Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65:1557–1565.

LinkOut - more resources