High sucrose/high fat diet (Quick Fat; QF) load obese type 2 diabetes model KK-Ay mice show signs of Diabetic Kidney Disease (DKD) development at 28 weeks of age, showing characteristics as a usseful DKD model.

It is extremely important to create a diabetes model that allows early analysis of severe renal lesions.

KK-Ay mice fed a high-scrose/high-fat diet (Quick Fat; QF) exhibited developed DKD pathology at 28 weeks of age. In the following, we will introduce the results of a study on the promotion of renal lesions in KK-Ay mice by QF loading.

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Method

Material and Method

• Animals:
  Male and Female KK-Ay mice (n=5/group)
  Male and Female db/db mice (n=5/group)、
  Male and Female C57BL/6J mice (n=5/group)
  
  
• Diets:
  CE-2(crude fat: 4.60%, energy: 340.2kcal)
  Quick Fat (QF) (crude fat: 14.35%, energy: 411.15kcal)

• All groups were bred from 6 weeks of age under the conditions of free choices diets, urine was collected at 13 weeks of age, and blood biochemistry and sacrificed at 14 weeks of age.

 

Measurement items

*Statistical analysis: EZR examined multiple comparisons using the Steel-Dwass method of the Kruskal-Wallis test.
Significant difference §p<0.05 vs. C57BL ,*p<0.05 vs. CE-2

 

Result

Body weight

 

Blood biochemistry (1)

 

Blood biochemistry (2)

 

Kidney weight

 

Glomerulus size

 

Kidney histopathological assessment in male db/db and KK-Ay mice

 

Kidney histopathological assessment in female db/db and KK-Ay mice

 

Kidney histopathological finding (HE staining)

 

Kidney histopathological finding (Sirius Red staining)

 

mRNA analyze

Tsutsui et al. (The 32nd Animal Meeting at the Japan Diabetic Nephropathy Study Group, 2021)

 

Result

• Hyperglycemia was observed in db/db and KK-Ay mice.
• Increased blood sugar level and hyperinsulinemia were observed in KK-Ay mice.
• QF feeding enhanced glomerular lesions in KK-Ay mice.
• In male KK-Ay mice, mesangial hyperplasia was observed with QF feeding.
• In female KK-Ay mice, QF feeding resulted in glomerular fibrosis.
• Tubulointerstitial lesions such as interstitial fibrosis was enhanced in QF-loaded KK-Ay mice.
• TIMP-1 was increased in QF-loaded KK-Ay mice.

 

Conclusion

The Q.F loaded KK-Ay mice are expected to be useful as a new DKD model.

 

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