PEG-Coated Ceria-Zirconia Nanoparticle Prevent Weight Gain and Obesity-Related Organ Damage Through Autophagy Flux Activation and ROS Scavenging

Abstract

Eun Kyung Kim,1,* Sang-Eun Hong,2,* Yun Seok Choi,1 Seong-Lan Yu,3 Jaeku Kang,4 Chang Gyo Park,4 Hoi Young Lee,4 Sung-Ki Lee,3,5 Dong Chul Lee,6 Won-Min Hwang,1 Sung-Ro Yun,1 Yohan Park,1 Moon Hyang Park,7 Junguee Lee,7 Kuk Ro Yoon,2 Lilach O Lerman,8 Se-Hee Yoon1 1Division of Nephrology and Department of Internal Medicine, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea; 2Department of Chemistry, Hannam University, Daejeon, Republic of Korea; 3Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea; 4Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea; 5Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, Republic of Korea; 6Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea; 7Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea; 8Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, 55905, USA*These authors contributed equally to this workCorrespondence: Se-Hee Yoon, Division of Nephrology and Department of Internal Medicine, Myunggok Medical Research Institute, College of Medicine, Konyang University, 164 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea, Email [email protected]: 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.Keywords: polyethylene glycol-coated ceria-zirconia nanoparticles, autophagy flux, obesity, lipid

Keywords

• polyethylene glycol-coated ceria-zirconia nanoparticles
• autophagy flux
• obesity
• lipid