Control of metabolic and cardiovascular function by the leptin–brain melanocortin pathway
Open accessAbstract
Obesity is recognized as a major worldwide health problem. Excess weight gain is the most common cause of elevated blood pressure (BP) and markedly increases the risk of metabolic, cardiovascular and renal diseases. Although the mechanisms linking obesity with hypertension have not been fully elucidated, increased sympathetic nervous system (SNS) activity contributes to elevated BP in obese subjects. Recent evidence indicates that leptin and the central nervous system (CNS) melanocortin system, including melanocortin 4 receptors (MC4R), play a key role in linking obesity with increased SNS activity and hypertension. Leptin, a peptide‐hormone produced by adipose tissue, crosses the blood–brain barrier and activates brain centers that control multiple metabolic functions as well as SNS activity and BP via the CNS melanocortin system. The crosstalk between peripheral signals (e.g., leptin) and activation of CNS pathways (e.g., MC4R) that regulate energy balance, SNS activity and BP represents an important target for treating obesity and its metabolic and cardiovascular consequences. © 2013 IUBMB Life, 65(8):692–698, 2013
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Leptin increases sympathetic nerve activity by binding to leptin receptors in the central nervous system and contributes to obesity-induced hypertension.
“In addition to regulating energy stores, leptin increases sympathetic nerve activity (SNA) by binding to leptin receptors (LepRs) in the CNS and contributes to obesity-induced hypertension6,121,122.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [122]
Leptin and the CNS POMC pathway appear to be important in obesity-induced SNS activation and hypertension.
“Although the role of many of these factors is still uncertain, leptin and the CNS POMC pathway appear to be important in obesity-induced SNS activation and hypertension17,80–82.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [81]
MC4R, activated mainly by α-MSH, is believed to be the key component of the brain melanocortin system's effects on sympathetic nervous system activation and blood pressure regulation.
“Although MC3Rs have been implicated in body weight regulation (mainly via effects on enery expenditure) and in preventing salt sensitivty of BP as previously discussed [22], MC4R, activated mainly by α-MSH, is believed to be the key component of the brain melanocortin system’s effects on SNS activation and BP regulation [9, 29, 30].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [30]
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Targeting the Brain Leptin-Melanocortin Pathway to Treat Heart Failure
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Androgens and Cardiovascular Diseases in Women
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Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system
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- Authors
- do Carmo, J. M., da Silva, A. A., Dubinion, J., Sessums, P. O., Ebaady, S. H., Wang, Z., & Hall, J. E.
- Affiliations
- Department of Physiology and Biophysics Center of Excellence in Cardiovascular‐Renal Research, University of Mississippi Medical Center Jackson MS USA
- University of Mississippi Medical Center (US)
- Corresponding author
- Hall, John E.
- Venue
- IUBMB Life
- Publisher
- Wiley
- Published
- 2013-07-11
- Volume
- 65
- Issue
- 8
- Pages
- 692-698
- ISSN
- 1521-6543 (ISSN-L)
- 1521-6551
- PMC
- PMC4077663
- OpenAlex
- W1508825525
- Cited by
- 36
- References
- 65
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 5
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- IUBMB Life (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01-HL-51971, P01HL051971)
- 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 › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, melanocortin system, melanocortin-4 receptor, obesity, hypertension, sympathetic activity, blood pressure regulation, energy balance, metabolic function, cardiovascular disease, blood-brain barrier
- MeSH terms
- Animals, Appetite, Blood Pressure, Humans, Hypertension, Obesity, Sympathetic Nervous System, Leptin, Receptor, Melanocortin, Type 4, Receptors, Leptin
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