Regulation of mTOR Pathway in Exercise-induced Cardiac Hypertrophy

Abstract

This study was designed to examine whether the mTOR signaling pathway would respond to long-term different intensity exercises and to observe the impact of exercise upon possible cardiac damage. Male Sprague Dawley rats were randomly divided into control group, moderate-intensity exercise group and high-intensity exercise group, and each exercise group had 4 observation time points (1-24 h). Exercise training lasted 8 weeks with a 2-day break for each week. Serum cTnI was measured by ELSIA and myocardium histology was assessed by HE and HBFP. The expressions of Akt, mTOR, p70(S6K) and their phosphorylated forms were determined by western-blot. Both exercises were effective at inducing cardiac hypertrophy, wherein magnitude increased with exercise intensity. The significantly high level of serum cTnI in the high-intensity group was accompanied by obvious myocellular abnormalities and ischemia in the myocardium. Significant activation of Akt, mTOR and p70(S6K) were observed in the moderate exercise group but not in the high-intensity exercise group. Results indicate that long-term high-intensity exercise training would induce cardiac hypertrophy accompanied by damage to the heart, entailing a risk of pathological changes. There might be a pivotal regulatory role of the mTOR signaling pathway on cardiac hypertrophy after long-term moderate exercise, but not after high-intensity exercise.

Inhibition of Receptor Interacting Protein Kinases Attenuates Cardiomyocyte Hypertrophy Induced by Palmitic Acid

“…It is recently reported that mTOR is involved in high-fat diet-Induced cardiac hypertrophy in mice [ 9 ], and AKT/mTOR mediates programmed necrosis in neurons [ 26 ]. Thus, we hypothesized that mTOR signaling participated in PA-induced necroptosis.…”

“…Moreover, mammalian target of rapamycin (mTOR), which is also essential for cardiomyocyte development, growth, and functions, regulates mitochondrial fatty acid utilization in the heart [ 8 ]. The AKT/mTOR signaling pathway has emerged as an important regulator in the pathogenesis of myocardial hypertrophy [ 9 ]. In cardiomyocytes, PI3K/mTOR/p70 (S6K) plays a critical role in the leptin-induced hypertrophy [ 10 ].…”

Cardiac Kinetophagy Coincides with Activation of Anabolic Signaling

“…Exercise potentiates anabolic signaling (i.e., phosphorylation of Akt and mTOR) in the heart (17), which is a well-accepted mechanism that inhibits autophagy under starvation, but this creates paradox because exercise also promotes kinetophagy. Therefore, we explored the question of whether kinetophagy occurs in parallel with mTOR activation.…”

Role of Exercise on Alleviating Pressure Overload-Induced Left Ventricular Dysfunction and Remodeling <i>via</i> AMPK-Dependent Autophagy Activation

“…The exercise protocol was based on previous research and effective for the promotion of cardiovascular adaptation. 11,12) Inhibitor administration: When the first bout of exercise training had been executed, autophagy inhibitor 3methyladenine (3-MA, TEM group, 100 mg/kg on alternate days) and Compound C (TEC group, 100 μg/kg every day) were separately administered by i.p. injection for 4 weeks.…”