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Tacrolimus Inhibits Hepatic Ferroptosis Through Modulating SIRT7-Dependent NRF2 Activation in Diabetes
Siqi Wang1, Wenbin Liu1, Feng Cui1
1State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Antioxidants (Basel, Switzerland)
|May 27, 2026
Summary
Tacrolimus (TAC) unexpectedly suppresses liver cell death called ferroptosis in type 2 diabetes. This finding offers a new therapeutic strategy for diabetic liver diseases by targeting ferroptosis.
Area of Science:
- Hepatology
- Metabolic Diseases
- Molecular Biology
Background:
- Type 2 diabetes is linked to hepatic lipotoxicity, oxidative stress, and ferroptosis, leading to liver damage.
- Current therapies for diabetic liver injury targeting ferroptosis are limited.
Purpose of the Study:
- To investigate tacrolimus (TAC) as a potential suppressor of hepatic ferroptosis in type 2 diabetes.
- To elucidate the molecular mechanisms underlying TAC's effect on ferroptosis.
Main Methods:
- Administration of TAC to db/db diabetic mice.
- Assessment of liver injury, fibrosis, inflammation, oxidative stress, and ferroptosis markers.
- Transcriptomic profiling of liver tissues.
- Investigation of the NRF2 and SIRT7 pathways in primary hepatocytes.
Main Results:
- TAC treatment significantly reduced liver injury, fibrosis, and inflammation in diabetic mice.
- TAC administration decreased oxidative stress and ferroptosis markers.
- Transcriptomic analysis revealed enrichment of glutathione metabolism pathways.
- TAC activated the NRF2 pathway in a SIRT7-dependent manner, inhibiting ferroptosis in hepatocytes.
Conclusions:
- Tacrolimus (TAC) unexpectedly inhibits hepatic ferroptosis via the SIRT7-NRF2 axis.
- TAC demonstrates potential as a therapeutic agent for diabetic liver diseases by modulating ferroptosis.
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