Aerobic exercise training prevents renal lipotoxicity associated with insulin resistance in mice

Abstract

Insulin resistance is associated with lipid accumulation in the kidney which leads to lipotoxicity, inflammation and renal damage. We investigated the potential of aerobic exercise training (AET) to prevent renal lipotoxicity in mice with diet‐induced insulin resistance. Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=5), cafeteria diet (CAF, n=5), chow‐fed trained (T, n=5), and cafeteria diet plus trained (CAFT, n=5). 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. AET 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. 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). Immunohistochemistry measurement revealed no difference in the expression of TGF‐β, Collagen IV and fibronectin. In the western blot analysis, CAF (2.12 ± 0.7 % vs. C) and CAFT (2.74 ± 0.5 % vs. C) groups showed a tendency (p=0.07) to increase the expression of IL‐6 compared to C group (1 ± 0.07 % vs. C). Furthermore, there was an increase in TNF‐α expression in the CAF (1.72 ± 0.05 % vs. C) and CAFT (1.46 ± 0.02 % vs. C) compared to C group. In conclusion, our results showed that cafeteria diet was able to induce renal lipotoxicity associated with insulin resistance and AET was efficient to prevent this damage independent of inflammatory profile changes.Support or Funding InformationFinancial Support: FAPESP # 2015/04948‐4.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.