Urinary titin as an early biomarker of skeletal muscle proteolysis and atrophy in various catabolic conditions

Abstract

Skeletal muscle atrophy impairs quality of life and increases the risk of disease, but current methods for assessment of muscle mass have several limitations. We here investigated the urinary concentration of a fragment of the muscle protein titin as a potential biomarker for the early detection of skeletal muscle atrophy. Four mouse models with different atrophy pathways were studied: those of cardiotoxin-induced acute muscle injury, cast-induced muscle immobilization, lipopolysaccharide-induced sepsis, and streptozotocin-induced diabetes. In all four models, urinary titin levels increased early, concurrent with or preceding upregulation of the atrophy-related genes for atrogin-1 and MuRF-1. The increase in the urinary titin concentration was thus associated with initial muscle damage and the onset of proteolysis, rather than with late-stage muscle wasting. Our findings suggest that urinary titin is a promising biomarker for detection of the onset of skeletal muscle catabolism and prediction of the subsequent development of atrophy in different catabolic states. Noninvasive measurement of urinary titin may therefore allow the earlier detection of skeletal muscle proteolysis compared with conventional techniques.