WITHDRAWN: Liraglutide suppresses ferroptosis by activating NRF2 target in type 2 diabetic cardiomyopathy

Recent studies have revealed that inhibiting myocardial ferroptosis could alleviated diabetic cardiomyopathy (DCM). Liraglutide (LIRA), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been confirmed to provide benefits in cardiovascular protection. However, the role of LIRA and its connection to myocardial ferroptosis in type 2 DCM remains largely unknown. In vivo , T2DM model was established using spontaneous diabetes Goto-Kakizaki (GK) rats. GK rats were administered LIRA (200 µg/kg/day) via hypodermic injection daily for 8 weeks. In vitro , H9C2 cells were treated with varying concentrations of glucose, LIRA, siRNA-Nrf2, Fer-1, or their combinations. LIRA improved glucose metabolism, cardiac remodeling, cardiac function, lipid peroxidation, and myocardial ferroptosis in diabetic rats. Additionally, we confirmed LIRA elevated the levels of ferroptosis-related proteins (Cyto-NRF2, Nu-NRF2, PTGS2, FTH-1, GPX4) in DCM. In vitro , high glucose exacerbated lipid peroxidation, decreased mitochondrial mass, and reduced the levels of ferroptosis-related proteins (Cyto-NRF2, Nu-NRF2, PTGS2, FTH-1, GPX4), leading to ferroptosis; these detrimental effects were rescued by LIRA treatment. Taken together, LIRA is a promising agent for the prevention and treatment of myocardial ferroptosis by activating NRF2 target in type 2 DCM.