PEG-coated ceria-zirconia nanoparticle prevent weight gain and obesity-related organ damage through autophagy flux activation and ROS scavenging

Abstract

Purpose: Obesity is becoming a global health problem that leads to serious complications. Despite numerous efforts to lose weight, achieving this goal is very difficult. Polyethylene glycol-coated ceria-zirconia nanoparticles (PEG-CZNPs) have attracted significant attention for their antioxidant properties, but they also have another valuable ability: restoring autophagy flux. In this study, we examined the therapeutic efficacy of PEG-CZNPs against obesity-induced organ complications and investigated the associated intracellular mechanisms. Methods: Palmitate was used to establish a cellular model of obesity in HK-2 cells. An obesity mouse model was created by feeding a high-fat diet (HFD). PEG-CZNPs were successfully synthesized, and their physicochemical characteristics and antioxidant activity were confirmed. A concentration of 10 μg/mL PEG-CZNPs was used to treat HK-2 cells. For the in vivo experiment, PEG-CZNPs were administered intraperitoneally at a dose of 10 mg/kg (2 mL/kg), twice per week, with normal saline used as the vehicle control. Biochemical analysis, histological staining, and immunohistochemistry were performed on the liver, kidney and adipose tissue of the mice at 12 and 24 weeks after initiating the HFD. Results: PEG-CZNPs successfully reduced lipid droplet accumulation palmitate-treated HK-2 cells by effectively restoring impaired autophagy flux. Reactive oxygen species (ROS), inflammation, and fibrotic changes caused by palmitate were also improved by PEG-CZNP treatment. In HFD-fed mice, PEG-CZNPs significantly reduced total body weight and the weights of the liver, kidney, and adipose tissue. They notably improved glucose tolerance and serum cholesterol levels while reducing tissue lipid accumulation. Additionally, PEG-CZNP treatment alleviated inflammatory cell infiltrations and fibrotic changes in the liver, kidney, and adipose tissue of HFD-fed mice. Autophagy flux was significantly enhanced, and ROS levels decreased in the tissue following PEG-CZNP treatment. Conclusion: PEG-CZNPs alleviated obesity-induced organ damage by decreasing intracellular lipid accumulation through the restoration of autophagy flux and ROS-scavenging activity.