The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
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]
In the citing paper
“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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Cites
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979
Self-citationLeptin receptor signaling in POMC neurons is required for normal body weight homeostasis
Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Elmquist, J. K., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.004 · Cited by 935
Leptin receptor missense mutation in the fatty Zucker rat
Phillips, M. S., Liu, Q., Hammond, H. A., Dugan, V., Hey, P. J., Caskey, C. T., & Hess, J. F. (1996) · Nature Genetics · doi:10.1038/ng0596-18 · Cited by 822
Role of leptin in fat regulation
Collins, S., Kuhn, C. M., Petro, A. E., Swick, A. G., Chrunyk, B. A., & Surwit, R. S. (1996) · Nature · doi:10.1038/380677a0 · Cited by 520
Leptin Activates Neurons in Ventrobasal Hypothalamus and Brainstem
Elmquist, J. K., Ahima, R. S., Maratos–Flier, E., Flier, J. S., & Saper, C. B. (1997) · Endocrinology · doi:10.1210/endo.138.2.5033 · Cited by 438
Dunbar, J. C., Hu, Y., & Lu, H. (1997) · Diabetes · doi:10.2337/diab.46.12.2040 · Cited by 414
Evidence That the Caudal Brainstem Is a Target for the Inhibitory Effect of Leptin on Food Intake
Grill, H. J., Schwartz, M. W., Kaplan, J. M., Foxhall, J. S., Breininger, J., & Baskin, D. G. (2002) · Endocrinology · doi:10.1210/endo.143.1.8589 · Cited by 395 · cited 1×
“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…”
BackgroundCano, G., Passerin, A. M., Schiltz, J. C., Card, J. P., Morrison, S. F., & Sved, A. F. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10643 · Cited by 337
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328
Brainstem projections of aortic baroreceptor afferent fibers in the rat
Ciriello, J. (1983) · Neuroscience Letters · doi:10.1016/0304-3940(83)90482-2 · Cited by 315
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Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2015) · Circulation Research · doi:10.1161/circresaha.116.305697 · Cited by 1,360
Obesity, kidney dysfunction and hypertension: mechanistic links
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0145-4 · Cited by 654
Structure, production and signaling of leptin
Münzberg, H., & Morrison, C. D. (2014) · Metabolism · doi:10.1016/j.metabol.2014.09.010 · Cited by 486
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Kotchen, T. A. (2010) · American Journal of Hypertension · doi:10.1038/ajh.2010.172 · Cited by 418
Obesity, kidney dysfunction, and inflammation: interactions in hypertension
Hall, J. E., Mouton, A. J., da Silva, A. A., Omoto, A. C. M., Wang, Z., Li, X., & do Carmo, J. M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa336 · Cited by 290
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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