Metabolic syndrome can induce
chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that
metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term
metabolic syndrome induced by a high fat and
fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and
drinking water enriched with
fructose (30%).
Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma
glucose, HDL,
LDL,
triglycerides and
cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by
inulin clearance and measure of
albuminuria. At sacrifice, kidneys and liver were collected.
Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of
type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in
albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal
inflammation (p-value=0.0217) but without renal
fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with
diabetic nephropathy also suggested absence of
diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of
metabolic syndrome on the development of
diabetic kidney disease.