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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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BackgroundConsumption of Green Tea Extract Results in Osteopenia in Growing Male Mice , ,
Iwaniec, U. T., Turner, R. T., Koo, S. I., Kaur, R., Ho, E., Wong, C. P., & Bruno, R. S. (2009) · Journal of Nutrition · doi:10.3945/jn.109.107201 · Cited by 24
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“Leptin is known to modulate various physiological processes in peripheral tissues through sympathetic nerve activation (Dunbar et al., 1997; Haynes et al., 1997; Takeda et al., 2002).”
BackgroundImmunity and the carotid body: implications for metabolic diseases
Conde, S. V., Sacramento, J. F., & Martins, F. O. (2020) · Bioelectronic Medicine · doi:10.1186/s42234-020-00061-5 · Cited by 24
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Fat cell metabolism: Insulin, fatty acids, and renin
Cassis, L. A. (2000) · Current Hypertension Reports · doi:10.1007/s11906-000-0072-5 · Cited by 24
“Moreover, recent studies suggest that in addition to leptin-mediated increases in sympathetic outflow to brown adipose tissue, leptin infusion resulted in increased sympathetic outflow to organs of cardiovascular relevance, including the kidney and the adrenal glands [ 31 ].”
BackgroundDoes leptin cause functional peripheral sympatholysis?
Jalali, A. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)01287-0 · Cited by 24
“2 Intravenous administration of leptin rapidly increases sympathetic nerve activity to brown adipose tissue and to the kidney, adrenal gland, and hindlimb”
BackgroundObesity Hypertension: Pathophysiological Role of Leptin in Neuroendocrine Dysregulation
Go, O., Liu, K., Villarreal, D., Spear, R. M., Freeman, R. H., Reams, G. P., & Weber, K. T. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31827ad5cf · Cited by 22
“Similar to the kidney, chronic hyperleptinemia indirectly may be important in the development of cardiac disease via sympathetic activation, pressor effects, enhancement of platelet aggregation, impairment of fibrinolysis and proangiogenic actions.(7,20,43) In addition, and although still controversial, leptin may be…”
BackgroundGuo, K., Mogen, J., Struzzi, S., & Zhang, Y. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90691.2008 · Cited by 22
Newer Biomarkers in Heart Failure
Gupta, S. K., Drazner, M. H., & de Lemos, J. A. (2009) · Heart Failure Clinics · doi:10.1016/j.hfc.2009.04.004 · Cited by 23
Rett Syndrome and Plasma Leptin Levels
Blardi, P., Lalla, A. D., D'Ambrogio, T., Zappella, M., Cevenini, G., Ceccatelli, L., Auteri, A., & Hayek, J. (2006) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2006.10.061 · Cited by 23
Corica, F. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)01288-2 · Cited by 22
“5 Additionally, there is increasing evidence to suggest the existence of a close relationship between sympathetic nervous system (SNS) activity and leptin”
BackgroundEffects of Chronic Nitric Oxide Inhibition on the Renal Excretory Response to Leptin
Villarreal, D., Reams, G. P., Samar, H., Spear, R. M., & Freeman, R. H. (2004) · Obesity Research · doi:10.1038/oby.2004.123 · Cited by 23
Temporal and regional onset of leptin resistance in diet‐induced obese mice
Rizwan, M. Z., Mehlitz, S., Grattan, D. R., & Tups, A. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12481 · Cited by 22
Understanding the Metabolic Syndrome: A Modeling Perspective
Khoo, M. C. K., Oliveira, F., & Cheng, L. (2012) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2012.2232651 · Cited by 24
“pressing appetite; however, this occurs at a price, since elevated leptin levels lead to increased sympathetic activity [141].”
Longitudinal changes of blood pressure after weight loss: factors involved
Flores, L., Vidal, J., Núñez, I., Rueda, S., Viaplana, J., & Esmatjes, E. (2014) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2014.04.028 · Cited by 22
Obesity, Hypertension, and the Heart
Good, D., Morse, S. A., Ventura, H. O., & Reisin, E. (2008) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.1559-4572.2008.00011.x · Cited by 22
Shih, C.-D., Au, L., & Chen, J. Y. H. (2003) · Journal of Biomedical Science · doi:10.1007/bf02256428 · Cited by 22
“Central application of leptin augments sympathetic outflow resulting in an increase in systemic arterial pressure (SAP) [20, 22, 33 ].”
BackgroundRole of extracellular signal-regulated kinases (ERK) in leptin-induced hypertension
Wójcicka, G., Jamróz-Wiśniewska, A., Widomska, S., Książek, M., & Bełtowski, J. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.11.029 · Cited by 22
Molecular mechanisms and neural mediators of leptin actionPreprint
Bodur, Ç., Duensing, A. M., & Myers, M. G. (2025) · Genes & Development · doi:10.1101/gad.352550.124 · Cited by 24
Adipose cell–adrenal interactions: current knowledge and future perspectives
Ronconi, V., Turchi, F., Bujalska, I. J., Giacchetti, G., & Boscaro, M. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.01.004 · Cited by 21
Zakaria, Z., Othman, Z. A., Nna, V. U., & Mohamed, M. (2021) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2021.1939387 · Cited by 23
Scott, R., Tan, T., & Bloom, S. R. (2013) · Vitamins and hormones · doi:10.1016/b978-0-12-407766-9.00007-9 · Cited by 20
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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