Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus
- Oregon Health & Science University, United States
Abstract
Whether leptin acts in the paraventricular nucleus (PVN) to increase sympathetic nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse. We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose tissue, because it induces the expression of its own receptor and synergizes with local glutamatergic neurons. PVN LepR are not expressed in astroglia and rarely in microglia; instead, glutamatergic neurons express LepR, some of which project to a key presympathetic hub, the rostral ventrolateral medulla (RVLM). In PVN slices from mice expressing GCaMP6, leptin excites glutamatergic neurons. LepR are expressed mainly in thyrotropin-releasing hormone (TRH) neurons, some of which project to the RVLM. Injections of TRH into the RVLM and dorsomedial hypothalamus increase SNA, highlighting these nuclei as likely targets. We suggest that this neuropathway becomes important in obesity, in which elevated leptin maintains the hypothalamic pituitary thyroid axis, despite leptin resistance.
Data availability
All data generated and analyzed are included in the manuscript. Source data files are provided for relevant figures.
Article and author information
Author details
Funding
National Institutes of Health (HL088552)
- Virginia L Brooks
National Institutes of Health (HL128181)
- Virginia L Brooks
National Institutes of Health (CA217989)
- Daniel L Marks
National Institutes of Health (NS099503)
- Andrei D Sdrulla
National Institutes of Health (DK112198)
- Christopher J Madden
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joel K Elmquist, University of Texas Southwestern Medical Center, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (TR01_IP00000151) of Oregon Health & Science University. All surgery was performed under isoflurane, alpha-chloralose, or pentobarbital anesthesia, and every effort was made to minimize suffering.
Version history
- Received: January 21, 2020
- Accepted: June 12, 2020
- Accepted Manuscript published: June 15, 2020 (version 1)
- Version of Record published: June 25, 2020 (version 2)
Copyright
© 2020, Shi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus
eLife 9:e55357.
https://doi.org/10.7554/eLife.55357
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