Differentiated contribution of fat pads to the prevention of insulin resistance through aerobic exercise training

Abstract

Increased white adipose tissue (WAT) is associated with the development of insulin resistance (IR), and this response may be due to impaired insulin signaling caused by excess of lipids. Aerobic exercise training (AET) prevents IR by improving lipid oxidation and glucose metabolism. Here we evaluated the relative contribution of fat pads to the prevention of IR through AET. 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). 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 (# 002/15). The body weight of T and CAFT groups were lower from the third week of experimental protocol compared to C. The CAF group had higher retroperitoneal (RP) and subcutaneous (SC) WAT weights compared to C, but the AET was able to prevent these increases in CAFT group. The T group presented lower periepididimal (PE) WAT compared to other groups, but interscapular BAT weight did not differ among groups. Cafeteria diet induced glucose intolerance and IR in CAF group (AUC: 35200± 1076 mg/dL/120min; kITT: 2,5 ± 0,17 %/min, respectively) compared to C group (AUC: 28333±1305 mg/dL/120min; kITT:, 3,7 ± 0,21 %/min respectively) during glucose and insulin tolerance tests, respectively, which were counteracted by AET in CAFT group (AUC: 28896 ± 1133 mg/dL/120min; kITT: 3,9 ± 0,33 %/min, respectively). Protein expressions of GLUT‐4 and t‐AKT were not different among groups, but p‐AKT reduced in T, CAF and CAFT groups compared to C in the PE‐WAT, and the p‐AKT/t‐AKT ratio was lower in CAFT compared to C in SC‐WAT. There were no differences in t‐AMPK and p‐AMPK expressions in SC‐WAT, but increase in t‐AMPK and p‐AMPK in T and CAFT groups compared to C and CAF groups in PE‐WAT. Histological analysis of the SC‐WAT showed the presence of multilocular adipocytes agglometares in T and CAFT groups, which is typical of WAT browning. In conclusion, the prevention of IR by AET is associated with lower visceral and subcutaneous WAT deposition, changes in the expression of metabolic proteins in PE‐WAT, such as reduction in p‐AKT and increase in t‐AMPK and p‐AMPK, and browning in the SC‐WAT.Support or Funding InformationFAPESP # 2015/04948‐4.