Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity

Obesity is increasing in pregnant women worldwide. Independent associations have been reported between maternal obesity and metabolic cardiorenal disorders in the offspring, including hypertension. In this study, using genetically modified mice, we have identified a role for the hypothalamic paraventricular nucleus (PVH) melanocortin system in the etiology of hypertension. We show that maternal obesity permanently resets the responsiveness of the central sympathetic nervous system via this pathway. We conclude that neonatal leptin exposure is the primary mediator, because exogenous neonatal leptin administration to pups of lean mice leads to the same phenotype mediated by PVH melanocortin-4 receptors. Thus, primary hypertension of sympathetic origin can result from early-life exposure to maternal obesity, and the melanocortin pathway presents a target for intervention

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