The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations

Abstract

Exercise, in the form of endurance or resistance training, leads to specific molecular and cellular adaptions not only in skeletal muscles, but also in many other organs such as the brain, liver, fat or bone. In addition to direct effects of exercise on these organs, the production and release of a plethora of different signaling molecules from skeletal muscle are a centerpiece of systemic plasticity. Most studies have so far focused on the regulation and function of such myokines in acute exercise bouts. In contrast, the secretome of long-term training adaptation remains less well understood, and the contribution of non-myokine factors, including metabolites, enzymes, microRNAs or mitochondrial DNA transported in extracellular vesicles or by other means, is underappreciated. In this review, we therefore provide an overview on the current knowledge of endurance and resistance exercise-induced factors of the skeletal muscle secretome that mediate muscular and systemic adaptations to long-term training. Targeting these factors and leveraging their functions could not only have broad implications for athletic performance, but also for the prevention and therapy in diseased and elderly populations.

Keywords: PGC-1alpha; endurance training; exercise; myokines; resistance training; secretome; skeletal muscle.

FIGURE 1

Schematic overview of examples of the endurance (left) and resistance (right) exercise-induced muscle secretome and its auto-, para-, and endocrine actions involved in training adaptation. See text for details. Abbreviations: AMPK, AMP-dependent protein kinase; Apelin, APJ Endogenous Ligand; BAIBA, β-aminoisobutyric acid; BDNF, Brain-derived neurotrophic factor; BNP, B-type or brain natriuretic peptide; EC, endothelial cell; ECM, Extracellular matrix; GDF3, macrophage-derived growth differentiation factor 3; GDNF, glial cell line-derived neurotrophic factor, IGF-1, Insulin-like growth factor-1; ILC2, innate lymphoid cells type 2; IL-6, Interleukin-6; IL-8, Interleukin-8; IL-13, Interleukin-13; LIF, Leukemia inhibitory factor; MOTS-c, mitochondrial ORF of the 12S ribosomal RNA type-c; MMP2, Matrix metalloproteinase-2; mTORC1, mammalian target of rapamycin complex 1; NMJ, Neuromuscular junction; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; SPARC, Secreted protein acidic and rich in cysteine; SPP-1, secreted phosphoprotein 1; TF, transcription factor; VEGF, Vascular endothelial growth factor; YAP1, Yes-associated protein 1.