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

Article

Samuelsson, A., Mullier, A., Maicas, N., Oosterhuis, N., Eun Bae, S., Novoselova, T., Chan, L., Pombo, J., Taylor, P., Joles, J., Coen, C., Balthasar, N. and Poston, L. 2016. Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity. Proceedings of the National Academy of Sciences. 113 (43), pp. 12298-12303. https://doi.org/10.1073/pnas.1607464113
TypeArticle
TitleCentral role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity
AuthorsSamuelsson, A., Mullier, A., Maicas, N., Oosterhuis, N., Eun Bae, S., Novoselova, T., Chan, L., Pombo, J., Taylor, P., Joles, J., Coen, C., Balthasar, N. and Poston, L.
Abstract

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

PublisherNational Academy of Sciences
JournalProceedings of the National Academy of Sciences
ISSN0027-8424
Electronic1091-6490
Publication dates
Online06 Oct 2016
Print25 Oct 2016
Publication process dates
Deposited12 Nov 2019
Accepted26 Aug 2016
Output statusPublished
Copyright Statement

For volumes 106–114 (2009–September 2017), the author(s) retains copyright to individual articles, and NAS retains an exclusive License to Publish these articles and holds copyright to the collective work.

Copyright & Usage: Freely available online through the PNAS open access option.

Additional information

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
1073/pnas.1607464113/-/DCSupplemental.

Digital Object Identifier (DOI)https://doi.org/10.1073/pnas.1607464113
LanguageEnglish
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