Meteorin-like/Meteorin-beta protects heart against cardiac dysfunction

Meteorin-like/Meteorin-beta (Metrnl/Metrn beta) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrn beta in cardiac disease is completely unknown. Here, we show that Metrn beta-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 Metrn beta in the heart prevents the development of cardiac remodeling. Furthermore, Metrn beta inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrn beta in cardiomyocyte cell cultures indicated an autocrine action of Metrn beta on the heart, in addition to an endocrine action. Moreover, Metrn beta is highly produced in the heart, and analysis of circulating Metrn beta concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.