Kidney Week

Abstract: FR-PO1191

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

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Kim, Eun Kyung, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Eun Kyung Kim, PhD

• Choi, YunSeok, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

YunSeok Choi, MS

• Song, Daun, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Daun Song, MD

• Hwang, Won Min, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Won Min Hwang, MD, PhD

• Yun, Sung-Ro, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Sung-Ro Yun, MD, PhD

• Park, Yohan, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Yohan Park, MD

• Yoon, Se-Hee, Konyang University College of Medicine, Daejeon, Korea (the Republic of)

Se-Hee Yoon, MD, PhD

Group or Team Name

• Div of Nephrology and Dept of Internal Medicine, Myunggok Medical Research Institute.

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.