The KLB rs12152703 variant confers protection against hepatic inflammation in patients with MASLD by boosting Klotho-beta expression
This study highlights the protective effect of a genetic variant in the Klotho-beta (<i>KLB</i>) gene in attenuating hepatic inflammation and disease severity in both adults and children with metabolic dysfunction-associated steatotic liver disease. The favorable clinical associations appear to be mediated by increased circulating and hepatic KLB protein levels. Consistently, KLB overexpression alleviates lipid overload in hepatocytes by modulating the expression of genes involved in lipid metabolism. Together, these findings support the FGF19/KLB axis as a promising therapeutic target for the treatment of severe metabolic dysfunction-associated steatotic liver disease.
Authors
- Francesca Tiano (ORCID: https://orcid.org/0000-0002-2962-981X)
- Valentina Doria (ORCID: https://orcid.org/0000-0001-5963-0734)
- Anna Ludovica Fracanzani (ORCID: https://orcid.org/0000-0001-5918-0171)
- Antonella Mosca (ORCID: https://orcid.org/0000-0001-9646-7462)
- C. De Stefanis
- Paola Dongiovanni (ORCID: https://orcid.org/0000-0003-4343-7213)
- Marica Meroni (ORCID: https://orcid.org/0000-0002-4161-4178)
- Miriam Longo (ORCID: https://orcid.org/0000-0002-9433-3492)
- Marco Maggioni
- Erika Paolini (ORCID: https://orcid.org/0000-0002-5654-8329)
- Sara Badiali
- Nadia Panera (ORCID: https://orcid.org/0000-0002-5365-3123)
- Ettore Mosca (ORCID: https://orcid.org/0000-0002-3102-5150)
- Anna Alisi
Institutions
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Bambino Gesù Children's Hospital (IT)
- Institute of Biomedical Technologies (IT)
- National Research Council (IT)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-12-23
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101717
- Primary Topic
- Parathyroid Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ospedale Pediatrico Bambino Gesù
- Ministero della Salute