Version 1
: Received: 21 October 2024 / Approved: 22 October 2024 / Online: 24 October 2024 (14:09:17 CEST)
How to cite:
Park, G. C.; Bang, S.-Y.; Kim, J. M.; Shin, S.-C.; Cheon, Y.-I.; Kim, K. M.; Park, H.; Sung, E.-S.; Lee, M.; Lee, J.-C.; Lee, B.-J. Ferroptosis in the Progression of Steatotic Liver Disease in Obese Mice: Implications of Its Inhibition. Preprints2024, 2024101737. https://doi.org/10.20944/preprints202410.1737.v1
Park, G. C.; Bang, S.-Y.; Kim, J. M.; Shin, S.-C.; Cheon, Y.-I.; Kim, K. M.; Park, H.; Sung, E.-S.; Lee, M.; Lee, J.-C.; Lee, B.-J. Ferroptosis in the Progression of Steatotic Liver Disease in Obese Mice: Implications of Its Inhibition. Preprints 2024, 2024101737. https://doi.org/10.20944/preprints202410.1737.v1
Park, G. C.; Bang, S.-Y.; Kim, J. M.; Shin, S.-C.; Cheon, Y.-I.; Kim, K. M.; Park, H.; Sung, E.-S.; Lee, M.; Lee, J.-C.; Lee, B.-J. Ferroptosis in the Progression of Steatotic Liver Disease in Obese Mice: Implications of Its Inhibition. Preprints2024, 2024101737. https://doi.org/10.20944/preprints202410.1737.v1
APA Style
Park, G. C., Bang, S. Y., Kim, J. M., Shin, S. C., Cheon, Y. I., Kim, K. M., Park, H., Sung, E. S., Lee, M., Lee, J. C., & Lee, B. J. (2024). Ferroptosis in the Progression of Steatotic Liver Disease in Obese Mice: Implications of Its Inhibition. Preprints. https://doi.org/10.20944/preprints202410.1737.v1
Chicago/Turabian Style
Park, G. C., Jin-Choon Lee and Byung-Joo Lee. 2024 "Ferroptosis in the Progression of Steatotic Liver Disease in Obese Mice: Implications of Its Inhibition" Preprints. https://doi.org/10.20944/preprints202410.1737.v1
Abstract
Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type mice (n = 8) and ob/ob (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, and this was normalized in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and Malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
