Myobolites: muscle-derived metabolites with paracrine and systemic effects

•Muscle secretes several metabolites with paracrine and endocrine signaling functions.•Skeletal muscle secretes adenosine to increase vasodilation.•Cardiomyocytes secrete cAMP which ultimately reduces cardiac hypertrophy and fibrosis.•Skeletal muscle secretes BAIBA to activate beta oxidation in liver and browning in adipose tissue.•Skeletal muscle secretes 3-HIB to induce the adjacent endothelium to transport fatty acids from blood into skeletal muscle.

Intracellular metabolism in skeletal muscle has been studied for more than a century and is the stuff of textbooks. In contrast, the extracellular secretion of metabolites by muscle cells, and their effects on non-muscle cells near or far, has been investigated much less extensively. Here, we describe a number of cases in which striated muscle secretes a metabolite that elicits complex responses in other cells or tissues, with involvements in normal physiology as well as obesity, type II diabetes, and cardiac remodeling. We focus on two recently identified secreted catabolic products of branched chain amino acid breakdown, β-aminoisobutyric acid and 3-hydroxyisobutyrate, and discuss common themes of inter-cellular signaling pathways driven by secreted metabolites.