The role of ACE2/Ang 1–7/Mas axis in the white adipose tissue for the prevention of obesity and insulin resistance through aerobic exercise training

Abstract

The activation of angiotensin converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang 1–7)/receptor Mas axis has been associated with cardiovascular and metabolic improvement, and may represent a new therapeutic target for cardiometabolic diseases. Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). In the present study we evaluated if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1–7)/Mas axis in the white adipose tissue (WAT). Adult male C57BL6/J mice were assigned into chow‐fed controls (C, n=5), chow‐fed trained (T, n=5), cafeteria diet (CAF, 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 the T and CAFT groups were lower from the third week of experimental protocol compared to C. The CAF group had higher retroperitoneal and subcutaneous (SC) fat pads weights compared to C, but the AET was able to prevent these increases in the CAFT group. Periepididimal (PE) fat pad weight was lower in T group compared to other groups. Cafeteria diet induced glucose intolerance and IR in CAF group (AUC: 35200± 1076 mg/dL/120 min; kITT: 2.5 ± 0.17 %/min) compared to the C group (AUC: 28333±1305 mg/dL/120 min; kITT: 3.7 ± 0.21 %/min), which were counteracted by AET in CAFT group (AUC: 28896 ± 1133 mg/dL/120 min; kITT: 3.9 ± 0.33 %/min). In the PE‐WAT, the activity of ACE2 was higher in CAF and CAFT groups compared to C and T groups, but Ang 1–7 concentration and Mas protein expression were not different among groups. In the SC‐WAT, no differences were found in ACE2 activity and Mas protein expression, but the Ang 1–7 concentration was lower in CAF and CAFT compared to C and T groups. In conclusion, the prevention of obesity and IR by AET was independent of the ACE2/Ang 1–7/Mas axis activation in the visceral and subcutaneous WAT.Support or Funding InformationSupport: FAPESP #2015/04948‐4; #2016/23783‐9.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.