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Receptor-mediated regional sympathetic nerve activation by leptin.
Open accessAbstract
Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure. Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known. We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Dawley rats. Intravenous infusion of mouse leptin over 3 h (total dose 10-1,000 microg/kg) increased plasma concentrations of immunoreactive murine leptin up to 50-fold. Leptin slowly increased sympathetic nerve activity to brown adipose tissue (+286+/-64% at 1,000 microg/kg; P = 0.002). Surprisingly, leptin infusion also produced gradual increases in renal sympathetic nerve activity (+228+/-63% at 1,000 microg/kg; P = 0.0008). The effect of leptin on sympathetic nerve activity was dose dependent, with a threshold dose of 100 microg/kg. Leptin also increased sympathetic nerve activity to the hindlimb (+287+/-60%) and adrenal gland (388+/-171%). Despite the increase in overall sympathetic nerve activity, leptin did not increase arterial pressure or heart rate. Leptin did not change plasma glucose and insulin concentrations. Infusion of vehicle did not alter sympathetic nerve activity. Obese Zucker rats, known to possess a mutation in the gene for the leptin receptor, were resistant to the sympathoexcitatory effects of leptin, despite higher achieved plasma leptin concentrations. These data demonstrate that leptin increases thermogenic sympathetic nerve activity and reveal an unexpected stimulatory effect of leptin on overall sympathetic nerve traffic.
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In the citing paper
“These findings are in contrast to the effect of leptin administration on increase natriuresis (49, 50) and sympathetic activity (51) in normal, nonobese leptin-resistant Zucker rats (51).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [51]
Experimental — accuracy not yet measuredIn the citing paper
“Plasma leptin concentration is highly correlated with SNA activity123, and acute leptin infusions increase SNA in the brown adipose tissue, adrenal glands and kidneys of rodents124.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [124]
In the citing paper
“acute leptin administration in rodents increased SNS activity in brown adipose tissue (BAT), the adrenal gland, and the kidneys84.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [84]
In the citing paper
“Acute leptin administration in rodents and humans increases renal and muscle SNS activity [45, 46] while chronic increases in plasma leptin levels, comparable to those found in severe obesity, caused sustained increases in BP and HR in rodents despite causing weight loss which would normally reduce BP [47].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [45]
In the citing paper
“In addition its effects on appetite and metabolism, leptin acts in the brain to produce receptor-mediated increases in regional sympathetic activity91.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [91]
In the citing paper
“Leptin is a potent appetite suppressant and, like insulin, stimulates the SNS.24,25”
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Self-citationCandidate genes for obesity and related phenotypes
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Zhang, F., Wang, S., Signore, A. P., & Chen, J. (2007) · Stroke · doi:10.1161/strokeaha.107.502302 · Cited by 1
Leptin and Cardiovascular Disease
(2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_10 · Cited by 1
Swoap, S. J., & Overton, J. M. (2003) · CRC Press eBooks · doi:10.1201/9780203507629.ch7 · Cited by 1
Fractal Analysis of the Binding and Dissociation of Different Compounds on Biosensor Surfaces
Sadana, A. (2006) · Elsevier eBooks · doi:10.1016/b978-044452784-4/50013-7
Ruokahalun säätely ja lihavuuden lääkehoito : lihavuuslääkkeiden tehoseulontamenetelmä seeprakalalla
Heine, S. (2014) · Työväentutkimus Vuosikirja
Clinical Applications of Leptin
Oral, E. A., & DePaoli, A. M. (2006) · Springer eBooks · doi:10.1007/978-0-387-31416-7_17
Song, X. (2015) · Työväentutkimus Vuosikirja
Fujiwara, C. T. H. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2014.tde-30102014-104249 · Cited by 1
Leptin: A Metabolic Perspective
Penn, D. M., Rooks, C. R., & Harris, R. B. S. (2007) · Wiley eBooks · doi:10.1002/9780470101001.hcn070
Role of Energy Expenditure in Regulation of Energy Homeostasis
Bachman, E. S. (2006) · Humana Press eBooks · doi:10.1007/978-1-59259-985-1_6
Bjursell, M. (2007) · Gothenburg University Publications Electronic Archive (Gothenburg University)
The battle against obesity : a role for thermogenic and satiating food ingredients
Diepvens, K. (2007) · Research Publications (Maastricht University) · doi:10.26481/dis.20071102kd
Influence of Diet on Stress Response and Behavior
Kitraki, E. (2011) · doi:10.1002/9781118083222.ch28
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Metadata
- Authors
- Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I.
- Affiliations
- University of Iowa (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-07-15
- Volume
- 100
- Issue
- 2
- Pages
- 270-278
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508189
- OpenAlex
- W2061340727
- Cited by
- 979
- References
- 29
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 15 · 2019: 13 · 2018: 11 · 2017: 31 · 2016: 29 · 2015: 25 · 2014: 44 · 2013: 34 · 2012: 43
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Wellcome Trust
- National Institutes of Health (5p50hl044546-05, 5r29hl043514-05)
- National Heart, Lung, and Blood Institute (HL-43514, HL-44546)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, P30DK025295)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- leptin, sympathetic activity, brown adipose tissue, renal sympathetic nerve activity, adrenal gland, thermogenesis, leptin receptor, Zucker fatty rats, norepinephrine, energy homeostasis
- MeSH terms
- Action Potentials, Adrenal Glands, Animals, Blood Glucose, Adipose Tissue, Brown, Disease Models, Animal, Hemodynamics, Hindlimb, Insulin, Kidney, Male, Obesity, Proteins, Rats, Zucker, Sympathetic Nervous System, Rats, Sprague-Dawley, Leptin, Rats
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