High, but not low, exercise volume shifts the balance of renin-angiotensin system toward ACE2/Mas receptor axis in skeletal muscle in obese rats

Abstract

Metabolic syndrome is a cluster of metabolic risk factors that is linked to central obesity, elevated blood pressure, insulin resistance (IR), and dyslipidemia, where the renin-angiotensin system (RAS) may provide a link among them. This study aimed to evaluate volume exercise effects comparing low vs. high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow (SC) diet or a high-fat (HF) diet for 32 wk. Animals receiving the HF diet were randomly divided into low exercise volume (LEV, 150 min/wk) and high exercise volume (HEV, 300 min/wk) at the 20th week. After 12 wk of aerobic treadmill training, the body mass and composition, blood pressure, glucose and lipid metabolism, RAS axes, insulin signaling, and inflammatory pathway were performed. HEV slowed the body mass gain, reduced intra-abdominal fat pad and leptin levels, improved total and peripheral body composition and inflammatory cytokine, reduced angiotensin II type 1 receptor expression, and increased Mas receptor protein expression compared with the HF animals. Sedentary groups (SC and HF) presented lower time to exhaustion and maximal velocity compared with the LEV and HEV groups. Both exercise training groups showed reduced resting systolic blood pressure and heart rate, improved glucose tolerance, IR, insulin signaling, and lipid profile. We conclude that the HEV, but not LEV, shifted the balance of RAS toward the ACE2/Mas receptor axis in skeletal muscle, presenting protective effects against the DIO model.

Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome

“…; Frantz et al . ), reduction of NO bioavailability and increase of oxidative stress (Hansel et al . ).…”

“…In the present study, MS was induced by prolonged HFD intake and resulted in a substantial reduction in capillary density in both skeletal muscle and the heart. Several mechanisms might be involved in this process, such as chronic low-grade inflammatory processes, mainly induced by the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 (Fain et al 2007;Frantz et al 2017), reduction of NO bioavailability and increase of oxidative stress (Hansel et al 2004). A pro-inflammatory and pro-oxidative profile initially promotes an inhibition of endothelium-dependent vasodilatation and increased leucocyte adhesion to the endothelium, impairing vascular reactivity, and subsequently, increases endothelial cell apoptosis, leading to microvascular rarefaction (Marui et al 1993;Bauersachs et al 1999).…”

Human Metabolism: A Regulatory Perspective

“…We also investigated some molecular pathways related to the deleterious effects of MS and recently reported increased protein expression of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) in an MS model induced by a high-fat diet (Frantz et al, 2017). It is well established that ACE and AT1R can exert deleterious effects on skeletal muscle, such as activation of inflammatory pathways, reactive oxygen species production, and impairment of insulin signalling (Zhou et al, 2015).…”

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“…Furthermore, these cytokines stimulate the synthesis of acute-phase proteins by liver hepatocytes (e.g. C-reactive protein [CRP] and fibrinogen), increasing systemic inflammation, platelet aggregation, and plasma viscosity, increasing risk of developing CVD and stroke (Gray and Kim, 2011;Frantz et al, 2017).…”