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Leptin Induces the Expression of the Leptin Receptor in the Hypothalamic Paraventricular Nucleus
Author(s) -
Pelletier Nicole E.,
Shi Zhigang,
Levasseur Peter R.,
Marks Daniel L.,
Brooks Virginia L.
Publication year - 2017
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.31.1_supplement.1039.5
Subject(s) - leptin , leptin receptor , endocrinology , medicine , receptor , hypothalamus , nucleus , chemistry , biology , obesity , neuroscience
We recently reported that nanoinjection of leptin into the hypothalamic paraventricular nucleus (PVN) elicits a slowly developing increase in sympathetic nerve activity (SNA), despite a well‐documented paucity of leptin receptors (LepR). This result suggests that leptin may induce the expression of its own receptor. To test this hypothesis, male SD rats (n=4) were anesthetized with α‐chloralose and were instrumented with electrodes for recordings of lumbar SNA (LSNA) and with femoral catheters for infusions and recordings of mean arterial pressure (MAP) and heart rate (HR). After collecting baseline data, leptin (60 ng in 60 nL) was injected into one side of the PVN, and the artificial cerebrospinal fluid (aCSF; 60 nL) vehicle was injected into the other side. Measurements of LSNA, MAP, and HR were continued for the following 6 hr. The animals were then deeply anesthetized, and brains were collected, flash frozen, sectioned (20 μm), and stored for subsequent in situ hybridization (ISH) assay of the LepR in PVN using antisense 33 P‐labeled LepR (corresponding to bases 10–407 of rat LepR). Levels of LepR in each side of the PVN were assessed in three sections by counting the total number of silver grains using custom‐designed software that subtracts background signal from selected regions. Unilateral injections of leptin into the PVN increased LSNA to 136±18 % control, MAP from 123±9 to 134±4 mmHg, and HR from 350±22 to 392±28 bpm (all P<0.05). LepR ISH revealed LepR signal on both sides of the PVN; however, the total number of silver grains was greater in the leptin‐treated side (2628±204) compared to the aCSF‐treated side (1996±47) (P<0.05). In conclusion, leptin induces the expression of its own receptor in the PVN. Support or Funding Information NIH HL128181, AHA 12GRNT11550018 and 15POST23040042.