Meteorin-like controls metabolic adaptations and physiological myocardial remodeling in pregnancy and lactation

The gestation-lactation period involves profound but reversible cardiac remodeling. Meteorin-like (Metrnl) has emerged as a regulator of cardiac metabolism in pathological settings, but its role in physiological reproductive adaptations remains unclear. This study aimed to define the contribution of Metrnl to cardiometabolic remodeling during the reproductive cycle.

Circulating Metrnl levels were assessed in murine and human late-pregnancy models. Wild-type (wt) and Metrnl knockout (Metrnl^-/- ) mice were analyzed across gestation, lactation, and weaning to evaluate cardiac structure and metabolism.

Late pregnancy increased circulating METRNL, largely of placental origin. In wt mice, cardiac hypertrophy induced by pregnancy was further enhanced during lactation and fully reversed after weaning. These changes were associated with increased fatty acid metabolism during gestation and its suppression during lactation, paralleling cardiac Metrnl expression and normalizing after weaning. By contrast, Metrnl^-/- mice showed exaggerated eccentric hypertrophy during gestation and lactation, with delayed regression post-weaning. This was accompanied by impaired metabolic flexibility and myocardial lipid accumulation, consistent with cardiac dysfunction.

Metrnl is essential for physiological cardiometabolic adaptation during the reproductive cycle, coordinating metabolic remodeling to ensure appropriate and reversible cardiac changes.