A PNPLA3–NACC1–RIPK3 pathway mediates macrophage necroptosis and inflammation in MASLD
The PNPLA3 148M variant promotes MASLD through a macrophage-specific NF-κB-NACC1-RIPK3 axis that enhances necroptosis and inflammatory signaling, thereby exacerbating hepatocyte steatosis and HSC activation. NACC1 emerges as a tractable therapeutic target for genetically at-risk individuals.
Authors
- Andrew C. Kwong (ORCID: https://orcid.org/0000-0002-0052-5881)
- Kyle O'Shaughnessy
- Xianfang Wu (ORCID: https://orcid.org/0000-0002-0701-4080)
- Lu Bian
- Zhuoying Feng
- Eun Hee Ha
- Xinjia Wang
- Lei Wang
Institutions
- Cleveland Clinic (US)
- Harvard University (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Case Western Reserve University (US)
Publication Details
- Journal
- Hepatology Communications
- Published
- 2026-01-21
- DOI
- https://doi.org/10.1097/hc9.0000000000000890
- Primary Topic
- Cell death mechanisms and regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00