Alleviating Obesity-Related Kidney Injury with Polyethylene Glycol-Capped Ceria-Zirconia Nanoparticles by Enhancing Autophagy Flux

Background: Obesity poses a significant contemporary health challenge, contributing to a range of complications. The underlying mechanisms remain incompletely understood, with obesity often triggering various pathological signals, such as lipotoxicity. Despite the considerable efforts by individuals to lose weight, achieving this goal is challenging. Polyethylene glycol-capped ceria-zirconia nanoparticles (PEG-CZNPs) have garnered attention for their antioxidant properties and their ability to restore autophagy flux. In this study, we investigated the protective effect of PEG-CZNPs against obesity-induced kidney injury. Methods: An in vitro model of obesity was established using palmitate in HK-2 cells. The change in lipid droplet deposition, reactive oxygen species (ROS), inflammation, and autophagy flux were evaluated using the oil-red O assay, western blotting, polymerase chain reaction, and immunofluorescence assays. An in vivo model of obesity was induced in mice through a high-fat diet. Biochemical analysis, histological stains, and immunohistochemistry were performed on the liver, kidney, and adipose tissue of the obese mice at 12 weeks after initiating the high-fat diet. Results: PEG-CZNPs successfully reduced lipid droplet deposition in HK-2 cells exposed to palmitate by restoring autophagy flux dysfunction. ROS, inflammation, and fibrotic change caused by palmitate were also improved by PEG-CZNPs treatment. PEG-CZNPs attenuated glucose intolerance and serum cholesterol levels in animal models of obesity. Additionally, PEG-CZNPs notably decreased cellular lipid droplet deposition. Conclusion: PEG-CZNPs alleviated obesity-induced kidney injury by reducing inflammation and oxidative stress and by decreasing organ lipid deposition through the restoration of autophagy flux function. Funding: Government Support – Non-U.S.