Abstract: FR-PO1011
High-Fat Diet Changes Lipid Profiles and Induces Podocyte Injury in Unilateral Kidney Model: Targeted Lipidomic and Kidney Podocyte-Specific Analysis
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Kim, You-Jin, Kyungpook National University, Daegu, Korea (the Republic of)
- Oh, Sehyun, Kyungpook National University, Daegu, Korea (the Republic of)
- Oh, Eun-Joo, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
- Yook, Ju-Min, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
- Ahn, Ji-Sun, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
- Lim, Jeong-Hoon, Kyungpook National University, Daegu, Korea (the Republic of)
- Cho, Jang-Hee, Kyungpook National University, Daegu, Korea (the Republic of)
- Kim, Chan-Duck, Kyungpook National University, Daegu, Korea (the Republic of)
- Park, Sun-Hee, Kyungpook National University, Daegu, Korea (the Republic of)
- Kim, Yong-Lim, Kyungpook National University, Daegu, Korea (the Republic of)
Background
We investigated that high fat diet changes lipidomic profiles and dysregulated lipid metabolism induces podocyte injury in unilateral nephrectomized mouse model using targeted lipidomics analysis and podocyte specific analysis.
Methods
Mice were randomized to undergo unilateral nephrectomy and fed standard or high-fat diets for 13 weeks. There were four groups; normal diet (ND), high-fat diet (HD), normal diet and received uninephrectomy (NDU), and high-fat diet and received uninephrectomy (HDU). After 13 weeks, lipidomics analysis was performed in podocytes isolated from the kidney. In vitro, CIHP-1 cells were treated with cholesterol ester for 24 hours.
Results
A high-fat diet accompanied by unilateral kidneys accelerated the increase in podocyte lipid droplets, glomerular size and tubular cell vacuole formation, resulting in deterioration of renal function. HDU showed different lipidomics profiles compared to other groups. Specifically cholesterol ester (CE), the CE20:4, increased significantly in HDU. Expressions of nuclear receptors, ABCA1, and CPT1A related to lipid metabolism decreased in the HDU and CIHP-1 cells treated with CE 20:4. Transmission electron microscopy confirmed loss of mitochondrial cristae, morphological changes and increased autophagosome formation in the HDU. In addition, reduction of NRF1/2 and increase of DRP1 were confirmed in HDU. In CIHP-1 cells stimulated with CE20:4, proteins related to mitochondrial, such as NRF1/2, PGC1-α, and PDK4 decreased, and mitochondrial fission was increased. Expressions of Beclin-1 and P62 were significantly increased in the HDU and CIHP-1 cells treated with CE 20:4. Kidney injury by such abnormal lipid metabolism induced renal fibrosis in the HDU.
Conclusion
High-fat diet increases lipid accumulation and lipid toxicity in podocytes induced renal structural and functional damage in the unilateral kidney model. In addition, lipotoxicity reduces mitochondria biogenesis, increases fission of mitochondria and increases incomplete action of autophagy.
Funding
- Government Support – Non-U.S.