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

Samuelsson, Anne-Maj, Mullier, Amandine, Maicas, Nuria, Oosterhuis, Nynke R., Eun Bae, Sung, Novoselova, Tatiana ORCID: https://orcid.org/0000-0002-2394-4667, Chan, Li F., Pombo, Joaquim M., Taylor, Paul D., Joles, Jaap A., Coen, Clive W., Balthasar, Nina and Poston, Lucilla (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. ISSN 0027-8424 [Article] (doi:10.1073/pnas.1607464113)

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

Item Type: Article
Additional Information: This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
1073/pnas.1607464113/-/DCSupplemental.
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 28128
Notes on copyright: 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.
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Depositing User: Tatiana Novoselova
Date Deposited: 12 Nov 2019 12:17
Last Modified: 20 Aug 2020 22:17
URI: https://eprints.mdx.ac.uk/id/eprint/28128

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