R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling
Given the hepatic/extrahepatic complications associated with MASLD (metabolic dysfunction-associated steatotic liver disease) and its high prevalence, it is crucial to decipher the precise molecular mechanisms regulating its pathogenesis to identify novel druggable targets. In this study, we demonstrate for the first time that hepatocyte RSPO2 plays a protective role against hepatic steatosis, fibrosis, and inflammation. <i>Rspo2</i> overexpression improves lipid metabolism, enhances AMPK-ACC signaling, and reduces hepatocyte apoptosis. Therefore, targeting RSPO2 in hepatocytes may represent a promising strategy to suppress MASLD.
Authors
- Naveed Pervaiz (ORCID: https://orcid.org/0000-0002-5848-8673)
- Prisha S. Patel
- Frank Park (ORCID: https://orcid.org/0000-0003-2324-2937)
- Ravi Varma Aithabathula (ORCID: https://orcid.org/0000-0002-1724-4218)
- Ishita Kathuria (ORCID: https://orcid.org/0000-0001-8545-3890)
- Santosh Kumar (ORCID: https://orcid.org/0000-0001-7846-5674)
- Lidya H Gebreyesus (ORCID: https://orcid.org/0000-0002-5540-637X)
- Cassandra Sprague (ORCID: https://orcid.org/0009-0004-1592-0974)
- Thouwa I. Samake (ORCID: https://orcid.org/0009-0005-8928-0209)
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- University of Tennessee Health Science Center (US)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-08-12
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101551
- Citations
- 2
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute