Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis

Abstract

Background: We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF).Methods: Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks.Results: Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL⁻¹120 min⁻¹; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min⁻¹, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO₂max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change.Conclusions: The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.