Receptor-mediated regional sympathetic nerve activation by leptin.

Haynes, W G; Morgan, D A; Walsh, S A; Mark, A L; Sivitz, W I

doi:10.1172/jci119532

Cited by 979Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Receptor-mediated regional sympathetic nerve activation by leptin.

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Haynes, W G, Morgan, D A, Walsh, S A, Mark, A L, Sivitz, W I·1997·Journal of Clinical Investigation

DOI 10.1172/jci119532PMC PMC508189

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Abstract

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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These findings are in contrast to the effect of leptin administration on increased natriuresis and sympathetic activity in normal, nonobese leptin-resistant Zucker rats.
“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]
The Results (A-SNA) report that leptin increased renal and brown-adipose sympathetic nerve activity in lean Zucker rats. But the Abstract and Discussion identify obese Zucker rats as leptin-resistant and report blunted responses in them, contrary to describing the nonobese rats as leptin-resistant. The sentence cites other sources, not this paper, for natriuresis. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Acute leptin infusions increase sympathetic nerve activity in brown adipose tissue, adrenal glands, and kidneys of rodents.
“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]
Acute leptin administration in rodents increased SNS activity in brown adipose tissue, adrenal gland, and kidneys.
“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]
Acute leptin administration in rodents and humans increases renal and muscle sympathetic nervous system activity.
“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]
Leptin acts in the brain to produce receptor-mediated increases in regional sympathetic activity.
“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]

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Self-citation

Authors: Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I.
Affiliations: University of Iowa (US)
ORCID: Haynes, W G
Morgan, D A
Mark, A L
Sivitz, W I
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-07-15
Volume: 100
Issue: 2
Pages: 270-278
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119532
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › 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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Receptor-mediated regional sympathetic nerve activation by leptin.

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