Meteorin-like/Meteorin-ß protects heart against cardiac dysfunction.

Meteorin-like/Meteorin-ß (Metrnl/Metrnß) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnß in cardiac disease is completely unknown. Here, we show that Metrnß-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus-mediated specific overexpression of Metrnß in the heart prevents the development of cardiac remodeling. Furthermore, Metrnß inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnß in cardiomyocyte cell cultures indicated an autocrine action of Metrnß on the heart, in addition to an endocrine action. Moreover, Metrnß is highly produced in the heart, and analysis of circulating Metrnß concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.