Protective effects of ferroptosis inhibition on high fat diet-induced liver and renal injury in mice.

As a complex and highly prevalent global public health problem, obesity is associated with multiple diseases, including liver and renal injury. As an iron-dependent form of cell death, ferroptosis is different from apoptosis and necrosis, which has been reported to participate in pathologic processes of many diseases. However, whether ferroptosis is involved in obesity-induced liver and renal injury remains unclear. Male C57BL/6 mice were fed with high-fat diet (HFD) or control diet for 16 weeks and treated with 5 mg/kg or 10 mg/kg ferroptosis inhibitor, ferrostatin-1 (Fer-1), for the last 8 weeks with results indicating that glutathione peroxidase 4 (GPX4) gene expression decreased in the liver and renal tissue of obese mice. Additionally, Fer-1 pretreatment prevented the obesity-induced decline of GPX4. More importantly, Fer-1 treatment attenuated HFD-induced pathological and functional impairment, fibrosis, inflammatory cell infiltration, and inflammatory cytokine expression in liver and renal tissues. In short, our results indicate that obesity can induce ferroptosis and ferroptosis inhibitor, Fer-1, thereby inhibiting obesity-induced liver and renal injury in mice. The study provides a new therapeutic direction for the complications of obesity.