Metformin and atorvastatin ameliorate MASH via the AMPK/NF-κB pathway
- 1Department of Interventional Therapy Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- 2Department of Radiology, Guang’anmen Hospital Jinan Branch, Jinan Municipal Hospital of Traditional Chinese Medicine, Jinan, Shandong, China
- 3Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
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: A MASH-like mouse model was established via HFD feeding combined with CCl4 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: Co-treatment with MET and ATO markedly alleviated FFA-induced lipid accumulation and TG/TC levels in HepG2 cells. Combination therapy in HFD/CCl4-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.
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BibTeX
@article{zhang2026metformin,
title = {{Metformin and atorvastatin ameliorate MASH via the AMPK/NF-κB pathway}},
author = {Bin Zhang and Na Li and Fang Liu and Guorui Wang and Quanwei Chen and Yiming Sun and Ni Yang and Hao Zhang and Jianjun Han},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1972846},
url = {https://doi.org/10.3389/fendo.2026.1972846},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metformin and atorvastatin ameliorate MASH via the AMPK/NF-κB pathway
AU - Bin Zhang
AU - Na Li
AU - Fang Liu
AU - Guorui Wang
AU - Quanwei Chen
AU - Yiming Sun
AU - Ni Yang
AU - Hao Zhang
AU - Jianjun Han
PY - 2026
DA - 2026/10/12
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1972846
UR - https://doi.org/10.3389/fendo.2026.1972846
AB - 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: A MASH-like mouse model was established via HFD feeding combined with CCl4 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: Co-treatment with MET and ATO markedly alleviated FFA-induced lipid accumulation and TG/TC levels in HepG2 cells. Combination therapy in HFD/CCl4-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.
SN - 1664-2392
ER -