The combination of high fat diet and diabetes exacerbates diabetic kidney disease in a novel mouse model — ASN Events
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The combination of high fat diet and diabetes exacerbates diabetic kidney disease in a novel mouse model (#201)

Wensheng Bao 1 , Danqing Min 1 2 , Sarah E Aamidor 1 , James Bonner 1 2 , Stephen M Twigg 1 2 , Nicholas A Shackel 3 4 , Susan V McLennan 1 2
  1. Discipline of Medicine and The Bosch Institute, The University of Sydney, Sydney, NSW, Australia
  2. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. Centenary Institute, Camperdown NSW, Camperdown , Sydney, NSW
  4. AW Morrow Gastroenterology and Liver Centre, Morrow Gastroenterology and Liver Centrer, Sydney, NSW, Australia

We previously reported that high fat diet combined with diabetes increases NASH progression and fibrosis in a novel mouse model but the effect of this combination on development of diabetic kidney disease is not known. Therefore, we aimed to investigate the effect of high fat diet and diabetes on development of kidney disease in this model.

C57BL/6 male mice (n=8/group) were fed a high fat diet (HFD:45%kCal fat) or chow (CHOW:12%kCal fat) at 15wks some animals were made diabetic (CHOW+DM or HFD+DM: STZ 2x65mg/kg). At termination (20wks) urine was collected for measurement of albumin/creatinine ratio and the kidneys were obtained for histological examination including quantification of podocyte number, inflammatory cell infiltrate and examination of matrix accumulation. Markers of matrix accumulation and turnover were quantified by qRT-PCR.

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HFD increased animal weight but this was abolished by diabetes. As expected diabetes and HFD increased blood glucose levels. Both HFD and HFD+DM increased albumin/creatinine ratio but only HFD+DM increased glomerular collagens I and IV and the glomerular sclerosis score (all by 2 fold vs CHOW, P<0.05). HFD and DM alone or in combination with HFD increased inflammatory cell infiltrate and decreased podocyte number (all P<0.05). Despite increased collagen I and IV accumulation in the kidney tissue of HFD+DM mice by IHC their mRNA levels were not altered. Expression of TIMP-1, an inhibitor of degradative enzymes was also increased in HFD+DM animals (P<0.05).

These data show that the combination of HFD+DM exacerbates development of kidney disease in this model. The increase in collagen accumulation is likely due to decreased matrix degradation.