The Brain Subfornical Organ Mediates Leptin-induced Increases in Renal Sympathetic Activity but not its Metabolic Effects
Open accessAbstract
The adipocyte-derived hormone leptin acts within the central nervous system to decrease food intake and body weight and to increase renal and thermogenic brown adipose tissue sympathetic nerve activity (SNA). Previous studies have focused on hypothalamic brain regions, although recent findings have identified leptin receptors (ObR) in a distributed brain network, including the circumventricular subfornical organ (SFO), a forebrain region devoid of a blood–brain barrier. We tested the hypothesis that ObR in the SFO are functionally linked to leptin-induced decreases in food intake and body weight and increases in SNA. SFO-targeted microinjections of an adenovirus encoding Cre-recombinase in ObR flox/flox mice resulted in selective ablation of ObR in the SFO. Interestingly, deletion of ObR in the SFO did not influence the decreases in either food intake or body weight in response to daily systemic or cerebroventricular administration of leptin. In line with these findings, reduction in SFO ObR did not attenuate leptin-mediated increases in thermogenic brown adipose tissue SNA. In contrast, increases in renal SNA induced by systemic or cerebroventricular administration of leptin were abolished in mice with SFO-targeted deletion of ObR. These results demonstrate that ObR in the SFO play an important role in leptin-induced renal sympathoexcitation, but not in the body weight, food intake, or brown adipose tissue SNA thermogenic effects of leptin. These findings highlight the concept of a distributed brain network of leptin action and illustrate that brain regions, including the SFO, can mediate distinct cardiovascular and metabolic responses to leptin.
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Mice lacking the leptin receptor in the subfornical organ exhibited a blunted leptin-induced renal sympathetic excitation.
“Indeed, mice lacking the leptin receptor in the subfornical organ exhibited a blunted leptin-induced renal sympathetic excitation.”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [42]
Leptin receptor signaling in the subfornical organ is involved in mediating renal sympathetic nerve activity in a selective manner.
“Leptin receptor signaling in the subfornical organ has also been involved in mediating renal sympathetic nerve activity in a selective manner (42).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [42]
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- Authors
- Young, C. N., Morgan, D. A., Butler, S. D., Mark, A. L., & Davisson, R. L.
- Affiliations
- University of Iowa (US)
- Venue
- Hypertension
- Published
- 2013-03
- Volume
- 61
- Issue
- 3
- Pages
- 737-744
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3832948
- OpenAlex
- W2119850839
- Cited by
- 58
- References
- 45
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 1 · 2017: 8 · 2016: 12 · 2015: 9 · 2014: 6 · 2013: 2
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Agriculture
- Roy J. Carver Charitable Trust
- National Institute for Health and Care Research
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL063887, HL096571, R01HL063887, HL-084207, P01HL084207, P01HL096571)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- leptin, subfornical organ, leptin receptor, renal sympathetic nerve activity, brown adipose tissue, thermogenesis, dietary intake, body weight, circumventricular organs, sympathetic nervous system, leptin signaling
- MeSH terms
- Animals, Body Weight, Brain, Adipose Tissue, Brown, Eating, Injections, Intraventricular, Kidney, Male, Subfornical Organ, Sympathetic Nervous System, Leptin, Gene Silencing, Thermogenesis, Mice, Receptors, Leptin
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