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High-fat/high-sucrose diet-induced renal changes in obese diabetic mice: a comparison with db/db and KK-Ay mice
Chika Oki1,2, Kinuko Uno2, Tomohiko Sasase1,2
1Biological/Pharmacological Research Laboratories, Takatsuki Research Center, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, Japan.
Abstract:
Many genetic and environmental factors are involved in the development and progression of diabetic kidney disease (DKD), and its pathology shows various characteristics. Animal models of DKD play an important role in elucidating its pathogenesis and developing new therapies. In this study, we investigated the pathophysiological features of two DKD animal models: db/db mice (background of hyperglycemia) and KK-Ay mice (background of hyperinsulinemia). Male and female mice were fed a high-fat/high-sucrose (HFS) diet for eight weeks. Two mouse models fed the HFS diet showed increases in urinary protein, kidney weight, and glomerular size, but these changes were pronounced in KK-Ay mice. Pathological examination revealed tubulointerstitial fibrosis in KK-Ay mice fed the HFS diet, but not in db/db mice. In addition, fat accumulation was observed in the macula densa of db/db mice and in the glomeruli of KK-Ay mice fed with the HFS diet. In conclusion, an HFS diet exacerbates renal lesions with tubulointerstitial fibrosis in KK-Ay mice, and KK-Ay mice fed an HFS diet are expected to be useful as a DKD model.
Insights
KK-Ay mice fed a high-fat/high-sucrose diet show exacerbated kidney damage, including fibrosis, making them a valuable model for diabetic kidney disease (DKD) research.
Area of Science:
- Nephrology
- Metabolic Diseases
- Animal Models
Background:
- Diabetic kidney disease (DKD) involves complex genetic and environmental factors.
- DKD pathogenesis and therapies are studied using animal models.
- Existing models may not fully capture DKD's diverse pathology.
Purpose of the Study:
- To investigate pathophysiological features of two DKD animal models: db/db and KK-Ay mice.
- To evaluate the impact of a high-fat/high-sucrose (HFS) diet on these models.
- To identify a suitable animal model for DKD research.
Main Methods:
- Male and female db/db and KK-Ay mice were fed an HFS diet for eight weeks.
- Evaluated urinary protein, kidney weight, and glomerular size.
- Conducted pathological examinations for tubulointerstitial fibrosis and fat accumulation.
Main Results:
- HFS diet increased urinary protein, kidney weight, and glomerular size in both models, more so in KK-Ay mice.
- Tubulointerstitial fibrosis was observed in HFS-fed KK-Ay mice, but not db/db mice.
- Fat accumulation occurred in db/db macula densa and KK-Ay glomeruli.
Conclusions:
- An HFS diet exacerbates renal lesions, including tubulointerstitial fibrosis, in KK-Ay mice.
- KK-Ay mice fed an HFS diet represent a promising model for studying diabetic kidney disease.
- This model can aid in understanding DKD pathogenesis and developing new treatments.
