## 4 Implication of Satellite Cells and Myonuclear Accretion
reported an elevation of Pax7 expression following a non-damaging low-intensity resistance exercise but expression of other markers of SCs activation (MyoD and myogenin) was upregulated only when a higher volume of the same exercise was achieved [212]. Studies using resistance exercises established that one bout of moderate to high intensity upregulates SCs activation with an increase in expression of myogenic factors, such as CD56, Pax7I, and MyoD [191]. The effect of resistance exercise on SCs activation is supported by numerous evidences and converge towards an increase in both SCs content and activation, as well as myonuclear accretion, a few hours after and until 4 days post-intervention [191]. Supporting that SCs implication is dependent on stimulus amplitude, exercise was recently found to induce SCs fusion  
Figure 4: Fusion-dependent and independent mechanisms of satellite cells during growth stimuli. Adult satellite cells (SCs) are in a quiescent state, expressing Pax7 (paired box protein 7) and CD56 (cluster of differentiation 56). Activation of SCs sets off the progression of myogenic lineage from quiescence to fusion. It requires MRF (myogenic regulatory factors) such as Myf-5 (myogenic factor 5), MyoD (myoblast determination protein D), myogenin, and MRF4 (myogenic regulatory factor 4). Whereas damaging exercises (high intensity endurance and eccentric contractions) promote SCs fusion in a regeneration process, exercise-induced hypertrophy requires SCs fusion and myonuclear accretion to increase fiber size. However, fusion-independent mechanisms may promote partial hypertrophy. The secretory functions of SCs seem to play a role in these mechanisms and in ECM (extracellular matrix) remodeling through miRNA-containing exosomes release. in a load-dependent manner whatever muscle typology [213]. However, in response to resistance training, the number of SCs increased mainly in type II myofib whereas type I myofib were almost not affected [211, 214, 215]. This is consistent with the fact that type II fibers have a greater contribution to hypertrophy and a better adaptive potential than type I. Noteworthy, while resistance training increases SCs pool, myonuclear accretion and muscle mass, endurance training does not necessarily promote myonuclear accretion or increase of muscle mass [209, 216, 217]. Endurance training appears more effective to increase satellite cell pool when exercise intensity is high, exercise duration being less susceptible to influence satellite cell content [209]. Besides exercise, numerous experimental conditions, such as steroids administration, nutritional interventions, or overloading models promote hypertrophy and conversely may attenuate atrophy in a disease setting. A great accrual of myonuclei was previously observed during a pronounced hypertrophic response following testosterone treatment in mice [218]. However, when a moderate muscle hypertrophy was induced by the same treatment, neither satellite cells number nor myonuclear accretion were found to enhance muscle fiber size [219]. Here, again, intensity of the stimulus seems to influence SCs activation and subsequent terminal differentiation and fusion with myofib. Furthermore, hypertrophic responses induced by various stimuli, from pharmacological to genetic interventions, were not always associated with increased myonuclear number. This was the case when hypertrophy was induced by genetic ablation of myostatin [220], treatment with the beta 2-adrenergic agonist clenburedol [221] and overexpression of the serine/threonine kinase Akt [222] (Figure 4). Of note, lysine supplementation, known to stimulate muscle growth, is associated with mTOR1 pathway activation and SCs proliferation/differentiation in piglets [223, 224]. In the past decade, [PERSON]'s group used Pax7-DTA-mediated ablation of SCs and suggested that muscle hypertrophic response to overloading could be independent of satellite cells intervention [225].