Aerobic exercise training prevents renal damage in insulin resistance mice

Abstract

Insulin resistance is associated with lipid accumulation in the kidney which leads to renal damage. We investigated the potential of aerobic exercise training (AET) to prevent renal damage in mice with diet‐induced insulin resistance. Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=7), cafeteria diet (CAF, n=7), chow‐fed trained (T, n=7), and cafeteria diet plus trained (CAFT=7). The standard chow diet contained 4% of kilocalories from fat, 55% from carbohydrate and 22% from proteins (Nuvilab®, Paraná, Brazil). The cafeteria diet contained 18.7% of kilocalories from fat, 56% from carbohydrate and 14.8% from proteins. PT was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (#18/2014). Cafeteria diet induced insulin resistance in CAF group compared to C group during insulin tolerance test, which was counteracted by AET in CAFT group. The glomerular filtration rate (GFR) increased by 88% in the CAF group compared to other groups. The water intake was lower in the CAF group (3.5 ± 0.3 mL) compared to the C (5.4 ± 0.5 mL), but there was no difference in urinary flow, urinary excretion of Na +, K +, Cl‐, total protein and urinary osmolarity. Histological analysis showed that CAF group increased intra‐renal lipid deposition (4.12 ± 0.48 %/area) compared to C group (1.70 ± 0.55 %/area), and that AET was able to prevent this increase in CAFT group (2.11 ± 0.51 %/area). There was a reduction in the Bowman's space in CAF group (104.4 ± 5.2 μm) compared to C group (154.3 ± 15.0 μm) and the AET prevented this decrease in CAFT (117.3 ± 5.3 μm). No changes were observed in the glomerular tuft area, however the CAF group showed a tendency to reduce Bowman's capsule area compared to C group (405.04 ± 21.23 vs. 470.7± 16.5 μm; p= 0.07). Protein expression of p‐AMPK increased in the CAFT group compared to the T group but there were no changes in t‐AMPK, t‐ACC, p‐ACC, PGC1‐α, SIRT‐1 expressions. In conclusion, our results showed that AET was efficient to prevent lipid deposition, the exacerbation of GFR and morphological impairments associated with insulin resistance. These responses may be associated, at least in part, with the increase in p‐AMPK in the kidney.Support or Funding InformationFAPESP # 2015/04948‐4.