Abstract: PUB106
Effect of a High-Fat Diet on the Progression of Diabetic Nephropathy and End-Organ Damage
Session Information
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Lowe, Melissa, University of South Florida Morsani College of Medicine, Tampa, Florida, United States
- Bohovyk, Ruslan, University of South Florida Morsani College of Medicine, Tampa, Florida, United States
- Levchenko, Vladislav, University of South Florida Morsani College of Medicine, Tampa, Florida, United States
- Klemens, Christine Anne, University of South Florida Morsani College of Medicine, Tampa, Florida, United States
- Staruschenko, Alexander, University of South Florida Morsani College of Medicine, Tampa, Florida, United States
Background
The high-fat Western diet (HFD) is a key contributor to the growing rate of obesity, which is a global health concern. Obesity increases the risk of metabolic syndrome leading to chronic illnesses like diabetes. Diabetic Nephropathy (DN) is a complication prevalent in Type 2 Diabetes (T2D), which eventually leads to end-stage renal disease or kidney failure. This study aimed to assess how HFD impacts diabetic severity and the progression of kidney, heart, and liver injury in T2D.
Methods
Young (12 weeks old) and aged (>38 weeks old) male and female Type 2 Diabetic Nephropathy (T2DN) rats, a non-obese T2D model, were placed on either normal (NFD) or HFD calorically balanced diets for 12 weeks. Glucose tolerance testing was performed every three weeks and total body weight (TBW), and 24-hour urine sampling were measured weekly. Kidney, heart, and liver functions were analyzed at the end of the study. RNA-Seq, lipidomic, and microbiome analyses were also performed.
Results
HFD males’ glucose intolerance and fasting blood glucose levels increased progressively and became significant by week 9 (aged rats) and week 6 (young rats). In contrast, glucose tolerance and fasting blood glucose were not affected in the females. The HFD did not affect 2-kidney/TBW ratios in all groups except young females. Heart weight/TBW ratios in females were significantly reduced on the HFD in both age groups. Studies are ongoing in young animals; however, old animals revealed a significant increase in albuminuria, KIM-1 staining, and medullary protein casts in the aged HFD female group, while there was no further progression of renal damage in the males. There was a significant increase in glucosuria in male HFD animals, and the HFD also increased lipid deposits in the liver for both sexes. No changes in cardiac fibrosis were observed. Microbiome analysis revealed a significant decrease in gut microbiota alpha diversity in males on HFD, while no significant changes were observed in females.
Conclusion
In conclusion, the HFD appears to have a more deleterious effect on glucose handling in both old and young T2DN males than in female rats. More profound renal effects in the aged female group are most likely due to already severe kidney injury in male T2DN rats, as we have previously reported.
Funding
- NIDDK Support