As the prevalence of obesity and metabolic disease continues to climb, the need for effective therapeutic interventions remains high. The growth of skeletal muscle (SkM) greatly influences systemic metabolism across the whole body, making this tissue an important therapeutic target to combat the rise of metabolic dysfunction. Transgenic rodent models of targeted SkM growth exhibit profound improvements in various remote tissues, including adipose tissue and the liver. It is currently unclear how selective stimulation of SkM growth alters the metabolism of distant tissues
however, evidence suggests that muscle-secreted factors may be involved. Here, we aim to provide basic biomedical researchers with a summary of the current knowledge regarding various muscle-secreted factors regulated by anabolic pathways and proteins in SkM, as well as their systemic metabolic effects, to implicate them in the whole-body metabolic effects of SkM growth. In this review, we also identify several knowledge gaps in this field, future directions of investigation, and implications for therapeutic interventions such as resistance exercise and pharmacology.