The metabolic role of corticotropin-releasing hormone receptor 2 and its UCN peptides: emerging therapeutic potential

Skeletal muscle is a highly plastic tissue that plays a crucial role in overall metabolic health, and in diseases such as obesity and type 2 diabetes. Recently, the importance of preserving muscle mass during weight loss has gained appreciation, especially with significant weight loss observed from incretin therapies, which includes loss of both fat and lean mass (Conte et al, JAMA 332:9-10, 2024). This has prompted investigation into pharmacological candidates that can prevent the loss of muscle mass seen during weight loss. Urocortins and their cognate receptors pose an interesting target, as recent evidence shows that they play a role in diseases such as heart failure, diabetes, and obesity. Urocortin treatment results in decreased food intake, muscle hypertrophy and improved skeletal muscle glucose uptake. However, the molecular mechanisms by which urocortins act have yet to be elucidated. The aim of this review is to highlight our current understanding of the effects of urocortins on metabolic adaptations.