Aerobic Exercise Training Prevents Obesity and Insulin Resistance Independent of Changes in the Skeletal Muscle ACE2/Ang 1‐7/Mas Axis.

Abstract

Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). Improvements in the oxidative capacity of skeletal muscle can mediate the protective effect of AET. Considering the role of angiotensin converting enzyme 2 (ACE2)/angiotensin 1‐7 (Ang 1‐7)/receptor Mas axis activation in reducing cardiometabolic diseases, the present study aimed to evaluate if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle. Adult male C57BL6/J mice were assigned into groups (n=10/group): chow‐fed controls (C), chow‐fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). 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 School of Arts, Science and Humanities, University of Sao Paulo, Brazil (#001/2016). The CAF group presented higher body weight gain and adiposity, glucose intolerance, IR and increased lipid deposition in the liver while AET prevented such damages in the CAFT group. Food consumption did not change among the groups. During the maximal physical exertion test, the T group increased VO2máx and both T and CAFT groups showed higher maximal speed, higher speed on the VO2máx and lower relative running cost compared to C and CAF groups. The enzymatic activity of citrate synthase and β‐hydroxyacyl‐CoA dehydrogenase (β‐HAD) in the soleus muscle increased in the T (352 ± 21.5 mmol/min/mg and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 mmol/min/mg and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 mmol/min/mg and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 mmol/min/mg and 46.7 ± 1.6 mmol/min/mg) groups. Protein expression of mitofusin 1, mitofusin 2 and dynamin related protein 1 (Drp1) did not change among groups. Also, no differences were observed in the ACE2 and Ang (1‐7) levels nor in the receptor Mas protein expression. In conclusion, the AET prevented the increase in body weight, adiposity and IR induced by cafeteria diet, improved the aerobic capacity and promoted the increase in oxidative enzymes activity in the soleus muscle. However, the adaptations induced by AET were not associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle.Support or Funding InformationSão Paulo Research Foundation (FAPESP #2015/04948‐4; #2016/23783‐9; #2016/20659‐5).