Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction

Abstract

Objectives: Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Materials and Methods: Male C57/BL6 mice were used to establish the MI model and divided into three groups: sedentary MI group, MI with aerobic exercise group and MI with resistance exercise group, sham-operated group was used as control. Exercise-trained animals were subjected to four-weeks of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis and degradation and cell apoptosis in gastrocnemius muscle were detected. And H2O2-treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1R inhibitor NVP-AEW541 and PI3K inhibitor LY294002 to explore the mechanism. Results：Exercises up-regulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling, increased the expressions of Pax7, myogenic regulatory factors (MRFs) and protein synthesis, reduced protein degradation and cell apoptosis in MI-mice. In vitro, IGF-1 up-regulated the levels of Pax7 and MRFs, mTOR and P70S6K, reduced MuRF1, MAFbx and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. Conclusion: AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation and cells apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt pathway.

A single-cell transcriptomic atlas of exercise-induced anti-inflammatory and geroprotective effects across the body

“…Conventionally, the majority of studies on exercise biology have focused on the skeletal muscle in an isolated setting, and led to the identification of a panel of critical signaling pathways induced by exercise, including IGF1/PI3K/Akt, AMPK, mTOR, and PGC-1α. 9 , 10 , 11 , 12 However, the molecular events associated with exercise, especially beyond the experimental paradigm of skeletal muscle, remain largely unknown. Hence, to identify exercise-associated molecular mechanisms that drive a broader spectrum of biological processes in a variety of tissues and organs, there is a need to complement the current “myocentric” paradigm by pursuing investigations of non-skeletal muscle tissues across the whole body.…”

Pea Peptide Supplementation in Conjunction With Resistance Exercise Promotes Gains in Muscle Mass and Strength

“…Myostatin is also known as growth differentiation factor 8. Myostatin inactivation can induce skeletal muscle hypertrophy, whereas its overexpression or systemic administration causes muscle atrophy ( 17 ). AMPK has also been considered to play an important role in regulating muscle mass and regeneration due to their effects on anabolic and catabolic cellular processes ( 18 , 19 ).…”

Molecular mechanisms of exercise contributing to tissue regeneration

“…PI3K/Akt signaling pathway Emerging evidence has revealed the essential contribution of PI3K/Akt signaling pathway to exercise-induced regeneration. 254,255 An array of growth factors has been reported to act as exerkines, such as IGF-1, 256 brain-derived neurotrophic factor (BDNF), 257 epidermal growth factor (EGF) 258 and their associated family, triggering the cellular responses via PI3K/Akt pathway. Amongst all the growth factors induced by exercise, the most widely studied is IGF-1.…”