Abstract: TH-PO0208
Role of Mitochondrial Dysfunction in the Progression of CKD in Obesity-Induced Hyperlipidemia
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Kumar, Vivek, Academy of Scientific and Innovative Research, Ghaziabad, UP, India
- Sharma, Prakriti, Academy of Scientific and Innovative Research, Ghaziabad, UP, India
- Patial, Vikram, CSIR - Institute of Himalayan Bioresource Technology, Palampur, HP, India
Background
Obesity is a major contributing factor that cause lipotoxicity in the renal cells and the progression of chronic kidney disease (CKD). In this study, the effect of hyperlipidemia on the kidney health was investigated using in vitro and in vivo models, targeting mitochondrial dysfunction and associated pathways.
Methods
In vitro studies were conducted on normal rat kidney epithelial cells (NRK-52E) and rat mesangial cells (RMCs). The cell lines were treated with free fatty acids (palmitic and oleic acid) to induce hyperlipidemia. In vivo, C57BL/6 mice were fed with a high-fat diet and fructose water for 16 weeks to induce obesity. Serum biochemical markers and histopathological changes were analyzed. Lipid accumulation in renal cells was quantified using Oil Red O and Nile Red staining. ROS generation and mitochondrial membrane potential (MMP) were analyzed using DCFDA and JC -1 dye, respectively. Transmission electron microscopy (TEM) of the kidney tissue was done. The expression of various obesity induced renal damage-associated genes and proteins was studied using qPCR and western blotting, respectively.
Results
In vitro studies showed an increased lipid accumulation, ROS generation, and altered MMP and mitochondrial structure in PO-treated renal cells. An increased expression of inflammatory (NFκB, IL-6, TNF-α) and fibrotic genes (COL4A, TGF-β, α-SMA) with altered expression of mitochondrial biogenesis genes (PGC-1α, NRF1, TFAM). In vivo study showed increased body weight in mice fed a high-fat diet, reduced glucose tolerance, and altered biochemical parameters (Urea, BUN, Creatinine, Protein, Albumin, cholesterol). Histopathological findings showed glomerular enlargement, loss of brush borders in the proximal tubules, early fibrotic changes, and glycogen deposition in the tubules. The high-fat diet group also showed increased adipocytes and hepatic steatosis. The high-fat diet increased levels of inflammatory (NFκB. IL-6, TNF-α) and fibrotic (COL4A, TGF-β, α-SMA) genes and proteins (NFκB, TGF-β, α-SMA) in kidney tissue. TEM analysis of kidney tissues revealed mitochondrial structural alterations and a decreased mitochondrial population in the high-fat group.
Conclusion
Overall, obesity plays a significant role in the development of chronic kidney disease by activating the inflammatory pathway and disrupting mitochondrial homeostasis in kidney.
Acknowledgment
The authors would like to acknowledge the Director, CSIR- Institute of Himalayan Bioresource Technology (IHBT), Palampur, India for providing the infrastructure and CSIR for funding the research in the form of CSIR-GATE fellowship and Academy of Scientific Innovative Research (AcSIR) for the academic affiliation
Funding
- Government Support – Non-U.S.