Evaluation of renal changes induced by high‐fat diet

Both experimental and clinical studies suggest that diabetes‐like complications develop at the prediabetic stage, prior to the development of overt hyperglycemia. We evaluated renal changes in high‐fat diet (HFD) fed mice, a model of prediabetes and alimentary obesity. Male C57Bl6/J mice were fed normal mouse chow or high‐fat (58 kcal% fat) diet for 16 wks. HFD feeding resulted in 46% increase in body weight, impaired glucose tolerance, and hyperinsulinemia. Kidney weight was increased by 11%. HFD‐fed mice displayed polyuria, 2.7‐fold increase in 24‐h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. They also displayed a dramatic (5.4‐fold) increase in urinary 8‐isoprostane excretion and 38% increase in renal cortex 4‐hydroxynonenal adduct accumulation, indicative of enhanced systemic and local oxidative stress. PAS‐positive substance accumulation (an index of mesangial expansion), TGF‐beta concentrations, and glucose and sorbitol pathway intermediate concentrations were indistinguishable between normal and HFD‐fed mice. In conclusion, HFD feeding causes prediabetic kidney disease, potentially via oxidative stress.