Work

Metformin and atorvastatin ameliorate MASH via the AMPK/NF-κB pathway

Year: 2026

Type: article

Abstract: Background: Despite being a globally prevalent chronic liver disease, MASLD currently lacks any approved pharmacotherapy. MET and ATO individually confer benefits against MASLD, but their combined therapeutic effects have seldom been investigated. The current work aimed to verify the therapeutic benefits of their combined intervention on MASH. Methods: injection, alongside an FFA-induced HepG2 steatosis model. Serum biochemical markers and inflammatory cytokines were measured, and lipid deposition was assessed by Oil Red O staining. Western blotting was performed to evaluate the expression of lipid metabolism-related proteins and AMPK/NF-κB signaling pathway components. Additionally, Compound C, a pharmacological inhibitor of AMPK, was used to verify the underlying molecular mechanism. Results: -induced MASH-like mice reduced body/liver weights, fasting glucose and HOMA-IR. Mechanistically, it downregulated lipogenic proteins SREBP-1 and HMGCR while upregulating fatty acid oxidation regulators CPT1A and PPARα. Additionally, it suppressed IL-6, TNF-α and IL-1β secretion via inhibiting NF-κB phosphorylation, thereby mitigating hepatic and cellular inflammation. Moreover, the combination enhanced AMPK phosphorylation, while the AMPK inhibitor Compound C largely abolished these protective effects. Conclusion: These observations indicate that the combined MET and ATO treatment exerts lipid-lowering and anti-inflammatory effects possibly via the AMPK/NF-κB signaling axis.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1972846