Acute kidney injury following fatty liver ischemia-reperfusion injury: indirect protection by hepatic ferroptosis inhibition
To understand the roles of ferroptosis in subsequent acute kidney injury (AKI) following hepatic ischemia-reperfusion injury (hIRI) in steatosis livers. The hIRI was induced in mice fed either a high-fat, high-sucrose diet (HFD) or a normal diet (ND)  to mimic the AKI commonly observed clinically after fatty liver transplantation. RNA sequencing was conducted to investigate the underlying mechanisms.  We found that apoptosis and inflammation are the prominent kidney injury mechanisms following fatty liver IRI. Although ferroptosis may not be directly involved in the renal injury, anti-ferroptosis intervention mitigates AKI, supporting the concept that ferroptosis-mediated liver injury may serve as the primary upstream trigger in this context. Overall design: The 10-week-old C57BL/6 mice (n=3 in each group) were fed with either a control diet (ND) or a high-fat diet (HFD) for 12 weeks before being subjected to 1hr hepatic ischemia-reperfusion injury (IRI) or a sham procedure.  Total 4 groups: HFD_IRI, HFD_sham, ND_IRI, and ND_sham. The mouse liver and kidney tissue were harvested in 6 hrs after ischemia injury.