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PVN Neuropeptide Y Contributes to the Sympathoexcitatory Effect of Leptin
Author(s) -
Shi Zhigang,
Li Baoxin,
Brooks Virginia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.652.26
Subject(s) - leptin , endocrinology , medicine , melanocortin , neuropeptide y receptor , hypothalamus , chemistry , appetite , tonic (physiology) , receptor , neuropeptide , biology , obesity
Intracerebroventricular (ICV) leptin administration increases sympathetic nerve activity (SNA) via a neuronal pathway that includes the paraventricular nucleus of the hypothalamus (PVN). PVN Neuropeptide Y (NPY) tonically inhibits SNA via type 1 receptors (Y1R). Leptin inhibits NPY neurons; however, whether leptin increases SNA in part by decreasing tonic PVN NPY inhibition is unknown. To test this hypothesis, we determined if blockade of PVN Y1R (Y1Rx) elicits smaller increases in lumbar SNA (LSNA) after ICV leptin (3 μg) in α ‐chloralose anesthetized male SD rats. LSNA was increased 90 min after ICV leptin (to 158±8% of control, n=5; P<0.05), but not after ICV artificial cerebrospinal fluid (aCSF; to 112±2%, n=5). In rats given ICV aCSF, subsequent PVN Y1Rx (bilateral BIBO3304, 60 pmol/60 nL) increased LSNA to 146±5 % of control (P<0.05). However, after ICV leptin, neither PVN Y1Rx (to 171±10 %) nor PVN aCSF (160±18 to 177±19%, n=5) significantly increased LSNA. These data support our hypothesis that leptin reduces tonic PVN NPY inhibition of LSNA. Leptin increases SNA in part via activation of PVN melanocortin 3/4 receptors (MC3/4R), and PVN presympathetic neurons express both Y1R and MC4R. Therefore, to test if leptin‐induced decreases in PVN NPY inhibition unmask MC3/4R excitation, we next determined if the MC3/4R agonist MTII increases LSNA more after Y1Rx. Bilateral PVN MTII (60 pmol/60 nL) did not alter LSNA (110±5% to 112±10 %, n=3); however, after Y1Rx, MTII increased LSNA from 124±3% to 164±6% (P<0.05, n=4). In conclusion, leptin decreases tonic PVN NPY inhibition of SNA, which may contribute to leptin‐induced increases in SNA by exposing enhanced MC3/4R excitatory drive of PVN presympathetic neurons. Supported by NIH HL088552 & AHA.