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Leptin Signaling in the Nucleus Tractus Solitarii Increases Sympathetic Nerve Activity to the Kidney
Open accessAbstract
The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We demonstrated previously that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin (0.25 to 1.00 μg) or saline into the NTS while recording SNA to kidney and brown adipose tissue. Microinjection of leptin into the commissural and medial subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley rats produced a dose-related increase in renal SNA (+112±15% with leptin 1 μg; n=7; P <0.001) but did not increase SNA to brown adipose tissue (−15±12%; P value not significant). This effect depended on intact functional leptin receptors, because it was not observed in Zucker obese rats that have a missense mutation in the leptin receptor. Rostral NTS injection of leptin failed to increase SNA, indicating that leptin signaling in the NTS is probably confined to the caudal NTS at the level of the area postrema. In summary, this study demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue. The study strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin.
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“Acute leptin injections into the brainstem NTS doubled RSNA and significantly increased BP, suggesting that brainstem LepRs also contribute to the effect of leptin on SNA138.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [138]
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“The LepR is expressed in multiple regions of the forebrain and hindbrain, including the hypothalamus, brainstem vasomotor centres and intermediolateral nucleus (IML) of the spinal cord119,135,138 (FIG. 5a).”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [138]
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“Discussion The major new findings from this study are as follows: (1) leptin receptor signaling in the NTS increases SNA to kidney but not to BAT; (2) sympathoactivation to microinjection of leptin into the NTS was associated with an increase in arterial pressure; and (3) the renal sympathetic nerve responses to NTS l…”
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Metadata
- Authors
- Mark, A. L., Agassandian, K., Morgan, D. A., Liu, X., Cassell, M. D., & Rahmouni, K.
- Affiliations
- University of Iowa (US)
- Venue
- Hypertension
- Published
- 2009-02
- Volume
- 53
- Issue
- 2
- Pages
- 375-380
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC2688398
- OpenAlex
- W2152899311
- Cited by
- 139
- References
- 24
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 3 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 8 · 2015: 8 · 2014: 16 · 2013: 20 · 2012: 14
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-084207, P01HL084207)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, nucleus tractus solitarius, sympathetic activity, renal sympathetic nerve activity, brown adipose tissue, leptin receptor, area postrema, distributed brain networks, leptin signaling, Zucker fatty rats, leptin receptor mutation
- MeSH terms
- Animals, Adipose Tissue, Brown, Disease Models, Animal, Dose-Response Relationship, Drug, Kidney, Microinjections, Obesity, Rats, Zucker, Sympathetic Nervous System, Signal Transduction, Rats, Sprague-Dawley, Solitary Nucleus, Mutation, Missense, Leptin, Rats, Receptors, Leptin
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