Arcuate neuropeptide y inhibits sympathetic nerve activity via multiple neuropathways

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH). First, we found that ArcN NPY/AgRP fibers closely appose PVN and DMH presympathetic neurons. Second, nanoinjections of NPY or an NPY receptor Y1 (NPY1R) antagonist into PVN or DMH decreased or increased SSNA, respectively. Third, blockade of DMH NPY1R reversed the sympathoinhibition elicited by selective, DREADD-mediated activation of ArcN NPY/AgRP neurons. Finally, stimulation of ArcN NPY/AgRP terminal fields in the PVN and DMH decreased SSNA. Considering that chronic obesity decreases ArcN NPY content, we propose that the ArcN NPY neuropathway to the PVN and DMH is pivotal in obesity-induced elevations in SNA.

Original languageEnglish (US)
Pages (from-to)2868-2880
Number of pages13
JournalJournal of Clinical Investigation
Volume127
Issue number7
DOIs
StatePublished - Jun 30 2017

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Neuropeptide Y
Neuropeptides
Arcuate Nucleus of Hypothalamus
Paraventricular Hypothalamic Nucleus
Hypothalamus
Viscera
Designer Drugs
Neurons
Peptides
Obesity
Pro-Opiomelanocortin
Arterial Pressure
Heart Rate
Dasyproctidae

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Arcuate neuropeptide y inhibits sympathetic nerve activity via multiple neuropathways. / Shi, Zhigang; Madden, Christopher (Chris); Brooks, Virginia.

In: Journal of Clinical Investigation, Vol. 127, No. 7, 30.06.2017, p. 2868-2880.

Research output: Contribution to journalArticle

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