Advertisement

 

 

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

Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity.
Author Information (click to view)

Samuelsson AS, Mullier A, Maicas N, Oosterhuis NR, Eun Bae S, Novoselova TV, Chan LF, Pombo JM, Taylor PD, Joles JA, Coen CW, Balthasar N, Poston L,


Samuelsson AS, Mullier A, Maicas N, Oosterhuis NR, Eun Bae S, Novoselova TV, Chan LF, Pombo JM, Taylor PD, Joles JA, Coen CW, Balthasar N, Poston L, (click to view)

Samuelsson AS, Mullier A, Maicas N, Oosterhuis NR, Eun Bae S, Novoselova TV, Chan LF, Pombo JM, Taylor PD, Joles JA, Coen CW, Balthasar N, Poston L,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Proceedings of the National Academy of Sciences of the United States of America 2016 Oct 6113(43) 12298-12303
Abstract

Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology. Here, we test the hypothesis that neonatal hyperleptinemia due to maternal obesity induces persistent changes in the central melanocortin system, thereby contributing to offspring hypertension. Working on the OffOb paradigm in both sexes and using transgenic technology to restore Mc4r in the PVH of Mc4rKO (Mc4rPVH) mice, we have now shown that these mice develop higher BP than Mc4rKO or WT mice. We have also found that experimental hyperleptinemia induced in the neonatal period in Mc4rPVH and WT mice, but not in the Mc4rKO mice, leads to heightened BP and severe renal dysfunction. Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health.

Submit a Comment

Your email address will not be published. Required fields are marked *

one + 5 =

[ HIDE/SHOW ]