Abstract: SA-PO0886
Long-Term High-Fat, High-Fructose Diet Promotes Kidney Injury and Persistent Inflammation in Prediabetic Rats
Session Information
- Health Maintenance, Nutrition, and Metabolism
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Iwatani, April, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Nilsson, Anna, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Lee, Katie, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Ortega, Michael, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Schunke, Kathryn Jaques, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
Background
Diabetic nephropathy has been extensively studied and is characterized by a progressive decline in renal function and glomerular membrane thickening. Distinct from diabetic nephropathy is diet-driven nephropathy without overt diabetes. The mechanisms that progress metabolic renal disease absent of diabetes hallmarks remain to be elucidated. Accumulating evidence has shown that chronic low-grade inflammation is a key mediator of sustained injury in metabolic diseases and may contribute to early renal pathogenesis. Here, we investigate the inflammatory mechanisms that progress renal injury after long-term high-fat high-fructose diet (HFFD) exposure.
Methods
Prediabetes was induced in male Sprague Dawley rats, beginning at 2 months of age and maintained for 10 months on a HFFD chow and 20% fructose water ad libitum. Controls received low-fat chow and regular water. Metabolic profiling included body weight, fasting glucose, and insulin tolerance tests. Renal injury was evaluated using serum/urine albumin and creatinine assays, blinded histopathologic scoring, PAS/Oil Red O/ picrosirius red staining, and immunohistochemical analyses of inflammatory, mitochondrial, and oxidative stress markers.
Results
HFFD-fed rats developed a phenotype similar to metabolic syndrome, showing significantly increased body weight, elevated fasting glucose, impaired insulin tolerance without pancreatitis. HFFD kidneys exhibited features of injury and tissue remodeling, including mesangial matrix expansion, fibrotic tissue accumulation, and intrarenal lipid accumulation. Leukocyte and macrophage populations were elevated in the HFFD group, accompanied by increased NFkB p65 expression in renal parenchymal cells. HFFD kidneys also showed altered expression of markers associated with mitochondrial dysfunction and oxidative stress.
Conclusion
Long-term HFFD exacerbates renal tissue remodeling and induces persistent renal inflammation, representing early pathogenic mechanisms linking chronic metabolic distress to kidney injury. These findings support that diet-induced prediabetes induction can drive progressive renal pathology.
Acknowledgment
This study was funded by NIH NIDDK R21DK133754 to M.O, and NIGMS P20GM113134 to M.O and K.S.
Funding
- NIDDK Support